Research progress on applications and mechanisms of osteogenesis effect of magnetic fields in oral field / 口腔疾病防治

@#Magnetic fields are safe and used in noninvasive physical therapies. Numerous studies have confirmed that magnetic fields have good osteogenic effects and certain value for clinical application in accelerating orthodontic tooth movement, promoting bone-implant integration, promoting fracture healing and improving the effects of distraction osteogenesis. Magnetic fields are expected to become applied as effective auxiliary methods for treating oral diseases. To support the clinical application of magnetic fields, this article reviews the applications of magnetic fields in the oral cavity, the biological effects on bone cells and the molecular mechanisms through which magnetic fields regulate bone metabolism. The biological effects of magnetic fields on bone cells include promoting osteogenesis by osteoblasts and mesenchymal stem cells and inhibiting bone resorption by osteoclasts. At the molecular level, bone cells sense and respond to magnetic stimulation, and through various mechanisms, such as displacement currents, Lorentz forces, and free radical pair effects, stimuli are transformed into biologically recognizable electrical signals that activate complex downstream signaling pathways, such as the P2 purinergic receptor signaling pathway, adenosine receptor signaling pathway, transforming growth factor-β receptor signaling pathway, mammalian target of rapamycin (mTOR) pathway, and Notch pathway. In addition, magnetic parameters, which are the factors affecting the osteogenic effects of magnetic fields, are discussed. However, the mechanisms of the osteogenic effects of magnetic fields are unclear, and further studies of these mechanisms could provide effective strategies for bone regeneration and periodontal tissue regeneration. In addition, considering the target of magnetic field therapies, combination with other drugs could lead to new strategies for the treatment of oral diseases.

Comparative Assessment of Contact Osteogenesis at the Titanium Implant-Bone Junction in Male Rabbits with Dissimilar Femoral Defects / Evaluación Comparativa de la Osteogénesis de Contacto en la Unión entre el Hueso y el Implante de Titanio en Conejos Macho con Defectos Femorales Diferentes

SUMMARY: Traumatized bone tissue has the capacity to repair itself so that it eventually regains its almost original form, even in the case of artificially inserted implants. The process that stays at the base of the regeneration is represented by osteogenesis or remote osteogenesis. The major difference between the two types of bone formation is the location of the cement line, which is located on the surface of the implant for contact osteogenesis and on the surface of the bone defect for remote osteogenesis. The aim of the present study was to assess the contact osteogenesis in the case of inserted titanium screws in holes with diameters of 1.8 mm and 1 mm respectively. The obtained results show, in the case of the groove with 1.8 mm that the newly proliferated bone represents 73.85 % of the total area, while in the case of the groove with 1 mm in diameter the value of the newly proliferated bone is 26.15 %. In conclusion, the insertion of titanium screws by self-tapping into the hole smaller than the core of the screw is accompanied by bone proliferation by contact osteogenesis much more modest than in the case of insertion into the hole larger than the core of the screw.

El tejido óseo traumatizado tiene la capacidad de reparar en forma espontánea, de modo que eventualmente recupera su forma casi original, incluso en el caso de implantes insertados artificialmente. El proceso que queda en la base de la regeneración está representado por la osteogénesis u osteogénesis a distancia. La principal diferencia entre los dos tipos de formación ósea es la ubicación de la línea de cemento, que se encuentra en la superficie del implante para la osteogénesis de contacto y en la superficie del defecto óseo para la osteogénesis remota. El objetivo del presente estudio fue evaluar la osteogénesis de contacto en el caso de tornillos de titanio insertados en forámenes con diámetros de 1,8 mm y 1 mm respectivamente. Los resultados obtenidos muestran, en el caso del surco de 1,8 mm que el hueso neoproliferado representa el 73,85 % del área total, mientras que en el caso del surco de 1 mm de diámetro el valor del hueso neoproliferado es del 26,15 %. En conclusión, la inserción de tornillos de titanio por autorroscantes en el foramen menor que el núcleo del tornillo se acompaña de una proliferación ósea por osteogénesis de contacto mucho más modesta que en el caso de la inserción en el foramen mayor que el núcleo del tornillo.

A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss

Abstract Objectives: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. Methods: The basic clinical data of Ol proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. Results: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the Ol progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. Conclusion: The clinical symptoms of the Ol proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for Ol patients with hearing loss. Level of evidence: Level 4.

Complicaciones relacionadas al manejo anestésico de pacientes pediátricos con osteogénesis imperfecta sometidos a procedimientos ortopédicos / Complications related to the anesthetic management of pediatric patients with osteogenesis imperfecta undergoing orthopedic procedures

Resumen: Introducción: la osteogénesis imperfecta es un trastorno sistémico del tejido conectivo, se caracteriza por una densidad ósea menor y variabilidad de la fragilidad ósea. Material y métodos: se realizó un estudio retrospectivo, observacional, descriptivo de casos consecutivos, cuyo objetivo principal fue determinar las complicaciones relacionadas al procedimiento anestésico en pacientes pediátricos con diagnóstico de osteogénesis imperfecta sometidos a procedimientos ortopédicos en el Hospital Infantil de México «Federico Gómez¼ mediante la revisión de expedientes clínicos. Se incluyeron pacientes con diagnóstico de osteogénesis imperfecta, menores de 18 años, sometidos a cirugía ortopédica electiva. Se utilizaron medidas de tendencia central y dispersión así como pruebas de hipótesis diversas. Resultados: se incluyeron 86 registros anestésicos. La mayoría del tipo III de osteogénesis imperfecta. La anestesia general balanceada fue la técnica más frecuente con intubación orotraqueal. De las complicaciones reportadas hubo intubación difícil en dos casos (2.3%). En seis casos (6.9%) se consideró ventilación difícil. Otra de las complicaciones reportadas fue el sangrado, encontrando un sangrado mayor al previsto en 33 casos (38.4%). Conclusiones: la anestesia requerida en los pacientes con osteogénesis imperfecta se llevó a cabo con un mínimo de complicaciones.

Abstract: Introduction: osteogenesis imperfecta is a systemic disorder of connective tissue, characterized by decreased bone density and variability of bone fragility. Material and methods: a retrospective, observational, descriptive study of consecutive cases was carried out, whose main objective was to determine the complications related to the anesthetic procedure in pediatric patients with a diagnosis of osteogenesis imperfecta undergoing orthopedic procedures at the «Federico Gómez¼ Children's Hospital of Mexico, through the review of clinical records. Patients diagnosed with osteogenesis imperfecta, under 18 years of age, undergoing elective orthopedic surgery, were included. Measures of central tendency and dispersion were used, as well as tests of various hypotheses. Results: 86 anesthetic records were included. Most of the type III of osteogenesis imperfecta. Balanced general anesthesia was the most frequent technique with orotracheal intubation. Of the reported complications, difficult intubation was found in two cases (2.3%). In six cases (6.9%) ventilation was considered difficult. Another of the complications reported was bleeding, finding bleeding greater than expected in 33 cases (38.4%). Conclusions: the anesthesia required in patients with osteogenesis imperfecta was carried out with a minimum of complications.

An Exploratory Study to Assess the Knowledge & Attitude of Parents Regarding Play Needs of Children (under 5 years of age) in Selected Hospital of Durg (C.G.)

Background-The human life has a distinct sphere– the world of play makes childhood more meaningful, happy & motivate the child to learn, develop & mature. Parents, teachers, nurses, psychologists are becoming increasingly aware of the importance of play and its influence upon bringing of children. The study was designed to assess the knowledge and attitude of parents regarding play needs of children. Materials & Methods- 100 couples were selected using purposive sampling technique. A structured questionnaire was prepared for assessing the knowledge & attitude of parents regarding play needs of children (under 5 years of age). Results- 20% of them had moderately adequate knowledge whereas 22% had moderately adequate attitude with. Knowledge & attitude of parents correlated. There is no significant association between socio demographic variables and knowledge except gender, religion, and mass media exposure, type of family, and monthly income and number of children as demographic variables. There is no significant association between socio demographic variables and attitude except gender, religion, qualification, type of family, and number of children as demographic variables. Conclusion-This study was conducted in Govt. Hospital of Durg (Chattisgarh) with the parents having children under 5 years of age. The findings of the study recommended the further interventional approaches regarding play needs of children. Parents need to be educated about meaning and importance of play for child. It creates awareness play know, attitudes, play needs, under five.

Use of the SARC-F Score as an Aid in Fragility Fractures Prevention / O uso do escore SARC-F como auxiliar na prevenção de fraturas por fragilidade

Abstract Objective The present study aimed to relate the strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) score with the presence or absence of fragility fracture in the population over 60 years of age. Methods The risk of sarcopenia was determined through the application of the SARC-F questionnaire, and the patients were divided into 2 groups, according to the occurrence or not of fragility fracture (n = 100). Results Thirty-two cases of distal radius fractures and eighteen cases of proximal femur fractures were identified. A higher score on the SARC-F is determinant between having or not a fragility fracture, estimating that for each point in the score there is a 70% increase in the chance of a patient having a fracture, regardless of age, gender, and body mass index (BMI). Conclusion There was a direct correlation between a higher score on the SARC-F and an increase in the chance of fragility fracture.

Resumo Objetivo O presente estudo teve como objetivo relacionar o escore strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) com a presença ou não de fratura por fragilidade na população acima de 60 anos. Métodos O risco de sarcopenia foi determinado por meio da aplicação do questionário SARC-F, sendo os pacientes divididos em 2 grupos, de acordo com a ocorrência ou não de fratura por fragilidade (n = 100). Resultados Foram levantados 32 casos de fratura de rádio distal e 18 casos de fratura de fêmur proximal. Uma maior pontuação no SARC-F determina bem entre ter ou não ter fratura por fragilidade, estimando que a cada ponto a mais no escore há um acréscimo de 70% na chance de o paciente ter fratura, independentemente da idade, sexo e índice de massa corporal (IMC). Conclusão Houve correlação direta entre uma maior pontuação no SARC-F e aumento na chance de fratura por fragilidade.

Functional status of individuals with osteogenesis imperfecta: data from a reference center

Abstract Objective: To evaluate the functional status of individuals with Osteogenesis Imperfecta (OI) followed up at a reference center in the state of Bahia. Materials and methods: This is an observational, cross-sectional, descriptive study, which evaluated individuals with OI, based on a non-probabilistic sampling. To assess motor function, the Motor Function Measure (MFM) score was used, in addition to the measurement of muscle strength using the Medical Research Council (MRC) score. Functional performance was measured using the Pediatric Assessment of Disability Inventory, Computerized Adaptive Testing (PEDI-CAT). Results: Thirty-one individuals aged between two and 18 years old were evaluated. The overall score of MFM was 74.2%, and the lowest score was found in participants with type III OI (56.3%). The median of the MRC index was 80. The mobility domain was the most affected in the PEDI-CATevaluation, with a mean T score of 23.9, (14.2 in type III OI). Conclusions: Among the evaluated individuals, functional alterations were identified, reduced global gross motor functionality and muscle strength, impacting the mobility domain, with the most relevant findings in individuals with type III OI.

Respiratory function of children and adolescents with osteogenesis imperfecta: respiratory muscle strength, forced vital capacity, and peak expiratory flow / Função respiratória de crianças e adolescentes com osteogênese imperfeita: força muscular respiratória, capacidade vital forçada e pico de fluxo expiratório

Abstract Objective: This study aims to evaluate the respiratory function of children and adolescents with osteogenesis imperfecta (OI) followed up at a referral center. Methods: A cross-sectional study was conducted with a non-probabilistic sample. Manovacuometry was performed with the measurement of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), and in addition, peak expiratory flow (PEF) and ventilometry were performed to measure forced vital capacity (FVC). Results: In total, 23 individuals were evaluated, with a mean age of 11.6±3.4 years, 56.5% of whom were females. Regarding the classification of OI, 56.5% of the sample belonged to type IV, 30.5% to type III, and 13% to type I. The mean MIP was 64.4% of the predicted, and the mean MEP was 56.2% of the predicted. Overall, the mean PEF was 213.9 L/min, but only 140.6 L/min in the OI type III group. Median FVC was 1.9 L, corresponding to 110% of the predicted. Conclusions: Respiratory function of the study subjects was altered, with respiratory muscle strength values lower than expected in the whole sample, and peak expiratory flow was significantly reduced in the OI type III group.

RESUMO Objetivo: Avaliar a função respiratória de crianças e adolescentes com osteogênese imperfeita (OI) acompanhados em um centro de referência. Métodos: Realizou-se um estudo de corte transversal, com amostragem não probabilística. Foi realizada manovacuometria com mensuração da pressão inspiratória máxima (PIM) e pressão expiratória máxima (PEM), além do pico de fluxo expiratório (PFE) e da ventilometria para a medida da capacidade vital forçada (CVF). Resultados: Foram avaliados 23 indivíduos, com média de idade de 11,6±3,4 anos, sendo 56,5% do sexo feminino. Com relação à classificação da OI, 56,5% da amostra pertencia ao tipo IV, 30,5% ao tipo III e 13% ao tipo I. A média de PIM foi de 64,4% do previsto, e a PEM foi de 56,2% do previsto. A média de PFE foi de 213,9 L/min, sendo 140,6 L/min no grupo de OI tipo III. A mediana da CVF foi de 1,9 L, correspondendo a 110% do previsto. Conclusões: A função respiratória dos indivíduos estudados encontrava-se alterada, com valores abaixo do esperado em toda a amostra para força muscular respiratória, além do PFE reduzido no grupo OI tipo III.

Treatment of osteogenesis imperfecta using the fassier-duval telescopic rod / Tratamento da osteogênese imperfeita com a haste telescópica fassier-duval

ABSTRACT Objectives: This study aimed to assess the treatment of patients with Osteogenesis Imperfecta (OI) operated on with a telescopic Fassier-Duval (FD) rod in a querterenario hospital from 2010 to 2020. Methods: We analyzed indication for surgical treatment, causes of reoperation, complications and the effectiveness of telescoping rod. Results: The results were compared with the literature and with the same parameters from a previous study which a different telescopic rod developed by the same authors. This was a retrospective study based on the analysis of digital and radiographic clinical records. Fifteen patients with 21 FD rods were evaluated, most were used on the femur (18 rods or 85.7%), eight patients were female (53.3%), with a mean age of 10.47 (3.92 to 16.44) years, most of whom had type III Sillence (46.7%), with a mean follow-up of 5.22 (1.43 to 7.02) years. Seven rods (33.3%) had complications. The main indication was for fracture (57.1%). Regarding the ability to telescope, we observed that 15 rods (71.4%) followed the child's growth. Conclusion: We had good results using FD rods, similar to the data found in the literature and the data obtained with our rod. Level of Evidence III,Retrospective comparative study .

RESUMO Objetivos: O objetivo deste estudo foi avaliar o tratamento de pacientes com Osteogênese Imperfeita (OI) operados com a haste telescopada de Fassier-Duval (FD) num hospital quaternário no período de 2010 a 2020. Métodos: Analisamos a indicação cirúrgica do tratamento, as causas de revisão, suas complicações e a eficácia na telescopagem da haste. Resultados: Os resultados foram comparados com a literatura e com os mesmos parâmetros de um artigo anterior no qual foi utilizada uma haste telescopada desenvolvida pelo nosso grupo. O estudo foi retrospectivo baseado na análise dos prontuários clínicos digitais e radiográficos dos pacientes. Quinze pacientes com 21 hastes de FD foram avaliados, sendo a maioria no fêmur (85,7%), oito pacientes eram do sexo feminino (53,3%), com média de 10,47 (3,92 a 16,44) anos, a maioria do tipo III de Sillence (46,7%), com tempo de seguimento médio de 5,22 (1,43 a 7,02) anos. Deste total, sete hastes (33,3%) apresentaram complicações. A principal indicação cirúrgica foram fraturas (57,1%). Em relação à telescopagem, observamos que 15 hastes (71,4%) acompanharam o crescimento da criança. Conclusão: No presente estudo verificamos bons resultados com as hastes de FD, à semelhança dos dados encontrados na literatura e dos dados encontrados com a haste do nosso serviço. Nível de Evidência III; Estudo retrospectivo comparativo .

Dental anomalies in individuals with osteogenesis imperfecta: a systematic review and meta-analysis of prevalence and comparative studies

Abstract Background Osteogenesis imperfecta (OI) is a rare genetic disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. OI is also known as brittle bone disease. Objective This study aims to describe the prevalence of dental anomalies (except dentinogenesis imperfecta) in individuals with OI, and compare the prevalence of dental anomalies between individuals with and without OI and between individuals with different types of OI. Search methods Searches in PubMed, Web of Science, Scopus, Ovid, and gray literature were performed in October 2022. Selection criteria Observational studies (with or without a comparison group) that evaluated the prevalence of dental anomalies in individuals with OI. Data collection and analysis: Data items were extracted by two authors. Quality assessment employing the Joanna Briggs Institute checklists and meta-analyses was conducted. Results were provided in prevalence values and odds ratio (OR) / 95% confidence interval (CI). Strength of evidence was determined. Results Eighteen studies were included. Most prevalent dental anomalies in individuals with OI included pulp obliteration (46.4%), dental impaction (33.5%), dental impaction of second molars (27%), and tooth agenesis (23.9%). Individuals with OI type III/IV had 20.16-fold greater chance of exhibiting tooth discoloration in comparison with individuals with OI type I (CI: 1.10-370.98). In comparison with the group without OI, the individuals with OI had 6.90-fold greater chance of exhibiting dental impaction (CI: 1.54-31.00). High methodological quality was found in 47% of the studies. Strength of evidence was low or very low. Conclusions Pulp obliteration, dental impaction, and tooth agenesis were the most prevalent dental anomalies in the OI group. Individuals with OI were more likely to have dental impaction than individuals without OI. Individuals with OI type III/IV (severe-moderate) are more likely to have tooth discoloration than individuals with OI type I (mild).

Protease-activated receptor type 2 activation downregulates osteogenesis in periodontal ligament stem cells

Abstract Protease-activated receptor-2 (PAR2) is associated with the pathogenesis of many chronic diseases with inflammatory characteristics, including periodontitis. This study aimed to evaluate how the activation of PAR2 can affect the osteogenic activity of human periodontal ligament stem cells (PDLSCs) in vitro. PDLSCs collected from three subjects were treated in osteogenic medium for 2, 7, 14, and 21 days with trypsin (0.1 U/mL), PAR2 specific agonist peptide (SLIGRL-NH2) (100 nM), and PAR2 antagonist peptide (FSLLRY-NH2) (100 nM). Gene (RT-qPCR) expression and protein expression (ELISA) of osteogenic factors, bone metabolism, and inflammatory cytokines, cell proliferation, alkaline phosphatase (ALP) activity, alizarin red S staining, and supernatant concentration were assessed. Statistical analysis of the results with a significance level of 5% was performed. Activation of PAR2 led to decreases in cell proliferation and calcium deposition (p < 0.05), calcium concentration (p < 0.05), and ALP activity (p < 0.05). Additionally, PAR2 activation increased gene and protein expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) (p < 0.05) and significantly decreased the gene and protein expression of osteoprotegerin (p <0. 05). Considering the findings, the present study demonstrated PAR2 activation was able to decrease cell proliferation, decreased osteogenic activity of PDLSCs, and upregulated conditions for bone resorption. PAR2 may be considered a promising target in periodontal regenerative procedures.

Effect of radiotherapy on the differentiation and osteogenic activity of mesenchymal stem cells on dental implants / Efeito da radioterapia na diferenciação e atividade osteogênica de células-tronco mesenquimais em implantes dentários

Objective: to evaluate the differentiation and gene expression of transcripts related to osteogenesis in a primary culture of Mesenchymal Stem Cells (MSCs) derived from rat femurs submitted to radiotherapy and the installation of pure titanium implants. Material and Methods: fifty-four rats received titanium implants in both femurs and were divided into three groups: Control: implant surgery (C); Implant + immediate irradiation (IrI), and Implant + late irradiation (IrL). Euthanasia occurred 3, 14, and 49 days after surgery. The bone marrow MSCs from the femurs were isolated and cultivated. The cell viability, total protein content, alkaline phosphatase (ALP) activity, and the formation of mineralization nodules and cellular genotoxicity were analyzed. The gene expression of Alkaline Phosphatase (phoA), Collagen 1 (COL1), Runt-related transcription factor 2 (RUNX2), Osterix (OSX), Osteopontin (OPN), Integrin ß1(ITGB1), Bone Sialoprotein (BSP), Osteonectin (SPARC), Osteocalcin (Bglap), Transforming Growth Factor ß-type (TGF-ß), Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), Interleukin-6 (IL-6), Apolipoprotein E (APOE) and Prostaglandin E2 synthase (PGE2) were evaluated by qRT- PCR. Results: ionizing radiation suppresses the gene expression of essential transcripts for bone regeneration, as well as cellular viability, as observed in the IrI and IrL groups. Conclusion: although this can lead to the loss of osseointegration and failure of the implant, the MSCs showed more activity at 49 days than at 3 and 14 days. (AU)

Objetivo: avaliar a diferenciação e expressão gênica de transcritos relacionados à osteogênese em cultura primária de MSCs derivadas de fêmures de ratos submetidos à radioterapia e instalação de implantes de titânio puro. Material e Métodos: cinquenta e quatro ratos receberam implantes de titânio em ambos os fêmures e foram divididos em três grupos: Controle: cirurgia de implante (C); Implante + irradiação imediata (IrI) e Implante + irradiação tardia (IrL). A eutanásia ocorreu 3, 14 e 49 dias após a cirurgia. As MSCs de medula óssea dos fêmures foram isoladas e cultivadas. Foram analisadas a viabilidade celular, teor de proteína total, atividade da fosfatase alcalina (ALP), formação de nódulos de mineralização e genotoxicidade celular. A expressão gênica de Fosfatase Alcalina (phoA), Colágeno 1 (COL1), fator de transcrição relacionado a Runt 2 (RUNX2), Osterix (OSX), Osteopontina (OPN), Integrina ß1 (ITGB1), Sialoproteína Óssea (BSP), Osteonectina (SPARC), Osteocalcina (Bglap), Fator de Crescimento Transformador tipo ß (TGF-ß), Fator Estimulante de Colônia de Granulócitos-Macrófagos (GM-CSF), Interleucina-6 (IL-6), Apolipoproteína E (APOE) e Prostaglandina E2 sintase (PGE2) foram avaliados por qRT-PCR. Resultados: a radiação ionizante suprime a expressão gênica de transcritos essenciais para a regeneração óssea, bem como a viabilidade celular, como observado nos grupos IrI e IrL. Conclusão:embora isso possa levar à perda da osseointegração e falha do implante, as MSCs apresentaram maior atividade aos 49 dias do que aos 3 e 14 dias (AU)

Osteogénesis imperfecta tipo III con presentación inusual / An unusual presentation of osteogenesis imperfecta type III

Introducción: la osteogénesis imperfecta (OI) es el trastorno óseo hereditario más común con incidencia mundial de 1 en 10.000 a 25.000 nacimientos, causado por mutaciones de los genes que codifican las cadenas del colágeno tipo I. La mayoría presenta patrón de herencia autosómico dominante. Las manifestaciones clínicas varían de asintomáticos con mayor predisposición a fracturas, talla normal y sin incidencia en la expectativa de vida, hasta alta letalidad perinatal con deformidades esqueléticas severas, incapacidad motora y talla muy baja. Objetivos: reportar un paciente con presentación inusual de OI tipo III con fracturas in útero para contribuir en la orientación diagnóstica. Caso clínico: recién nacido con sospecha in útero de OI tipo II, nació a término vía cesárea, Ballard de 37 semanas y bajo peso con fracturas múltiples y defectos de osificación (braquicefalia). A los 4 meses con sobrevida mayor a la esperada, presentaba escleróticas grisáceas, braquicefalia, fontanelas amplias, fragilidad ósea generalizada y deformidades angulares en extremidades; confirmándose la OI tipo III mediante secuenciación exómica. Conclusiones: el diagnóstico de la OI se basa en la clínica y las características típicas. La supervivencia, los hallazgos radiográficos y el resultado de los estudios genéticos moleculares permiten la adecuada clasificación.

Introduction: osteogenesis imperfecta (OI) is the most common hereditary bone disorder with a global incidence of 1 in 10,000 to 25,000 births. OI is caused by mutations in the genes encoding the chains of collagen type I and is mostly inherited in an autosomal dominant manner. Clinical manifestations vary from asymptomatic with increased propensity to fractures, normal stature and no impact on life expectancy, to high perinatal lethality, severe skeletal deformities, motor disability and very short stature. Objectives: to report a case of an unusual presentation of OI type III in an infant who had in utero fractures, as a diagnostic resource. Case: a full-term infant born via cesarean section, with suspected in utero OI type II, Ballard score: 37 weeks, low weight and multiple fractures and ossification defects (brachycephaly). At 4 months, a higher survival than the expected, he presented greyish sclerae, brachycephaly, large fontanels, generalized bone fragility and bowing of extremities; OI type III was confirmed by exome sequencing. Conclusions: OI diagnosis is based on the clinical and typical features of the disorder. Survival, radiographic findings and molecular genetic testing allow an adequate classification.

Estrogen deficiency influences TNF-α and IL-1ß gene expression in the odontogenic region of dental hypofunctional condition / A deficiência de estrógeno influencia a expressão gênica de TNF-α e IL-1ß na região odontogênica de dentes em hipofunção

Objetivo: Evidências científicas sugerem que a deficiência de estrógeno e fatores genéticos influenciam o desenvolvimento do sistema estomatognático. Este estudo teve como objetivo avaliar a influência da deficiência de estrógeno na expressão gênica de TNF-α, IL-1ß, IL-6 e IL-10 durante o desenvolvimento dentário em modelo murino. Material e Métodos: Ratas Wistar Hannover foram divididas em dois grupos de acordo com a intervenção recebida: Grupo Hipoestrogenismo - cirurgia de ovariectomia e Grupo Controle - cirurgia fictícia. Para avaliar o desenvolvimento dentário, o incisivo inferior foi escolhido. O modelo de hipofunção dos incisivos inferiores foi realizado por ajuste incisal. O incisivo homólogo exercia hiperfunção dentária. Os animais foram avaliados durante todo o período puberal. Após a eutanásia, as hemimandíbulas foram removidas para avaliar a expressão gênica do TNF-α, IL-1ß, IL-6 e IL-10 na região odontogênica dos incisivos por meio de PCR em tempo real. Foi realizado o teste de Kruskal-Wallis e o pós-teste de Dunn. O nível de significância foi de 5%. Resultados: Houve diferenças estatisticamente significativas na expressão gênica de TNF-α e IL-1ß entre os grupos hipoestrogenismo e controle sob condição de hipofunção dentária (p=0,0084, p=0,0072, respectivamente). Conclusão: A deficiência de estrógeno influencia a expressão gênica de TNF-α e IL-1ß na região odontogênica de dentes hipofuncionais (AU)

Objective: Scientific evidence suggests that estrogen deficiency and genetic factors have an influence on the development of the stomatognathic system. This study aimed to evaluate the influence of estrogen deficiency on the gene expression of TNF-α, IL-1ß, IL-6 and IL-10 during dental development in a murine model. Material and Methods: Wistar Hannover rats were divided into two groups according to the intervention received: Hypoestrogenism Group - ovariectomy surgery and Control Group - fictitious surgery. To evaluate the dental development, the lower incisor was chosen. The mandibular incisor hypofunction model was performed by incisal adjustment. The homologous incisor exerted a hyperfunction. The animals were evaluated throughout the pubertal period. After euthanasia, the hemimandibles were removed to evaluate the gene expression of the TNF-α, IL-1ß, IL-6 and IL-10 in the odontogenic region of the incisors through real time PCR. Kruskal-Wallis test and Dunn's posttest were performed. The level of significance was 5%. Results: There were statistically significant differences of TNF-α and IL-1ß gene expression between the hypoestrogenism and control groups under hypofunction condition (p=0.0084, p=0.0072, respectively). Conclusion: Estrogen deficiency influences TNF-α and IL-1ß gene expression in the odontogenic region of the hypofunctional teeth. (AU)

Cirugía en coxa vara por osteogénesis imperfecta. Reporte de dos casos / Coxa vara surgery for osteogenesis imperfecta. A report of two cases

Introducción. La coxa vara es una disminución del ángulo cervicodiafisiario (<110°) y se puede presentar hasta en el 10% de los pacientes con osteogénesis imperfecta (OI), siendo más frecuente en el tipo III. Sus manifestaciones clínicas son alteración en la marcha, acortamiento de la pierna, genu valgo y dolor.Presentación de los casos. Varones de 13 años y 8 años con OI tipo III, signo positivo de Trendelenburg, movilidad articular adecuada y antecedentes de fracturas recurrentes y cirugías previas por deformidades en los que se realizó cirugía para la corrección de coxa vara. Se realizó una evaluación radiográfica y una funcional (escala de Harris) a los 6 y 68 meses de la cirugía, respectivamente.En el caso 1 se logró una corrección de 46° en el ángulo cervicodiafisiario (ángulo inicial: 84°; ángulo final: 130°) y el puntaje en la escala de Harris fue de 70 puntos. En el caso 2, se logró una corrección de 50° (82° vs. 132°), con un puntaje en la escala de Harris de 68 puntos. Conclusiones. la técnica de corrección mediante osteotomía subtrocantérica y la utilización de clavo endomedular y agujas de Kirschner es una opción efectiva para el tratamiento de coxa vara en pacientes con osteogénesis imperfecta

Introduction. Coxa vara is a deformity characterized by a decrease in the neck-shaft angle (<110°) that can occur in up to 10% of patients with osteogenesis imperfecta (OI), being more frequent in type III OI. Its clinical manifestations are gait disturbance, leg shortening, genu valgum, and pain.Case presentation. Male patients aged 13 and 8 years presenting with type III OI, positive Trende-lenburg sign, adequate joint mobility, and a history of recurrent fractures and previous surgeries for deformities, including surgery for coxa vara correction. Radiographic and functional evaluation (Harris scale) were performed 6 and 68 months after surgery, respectively.In the first case, a correction of 46° was obtained (initial angle: 84°; final angle: 130°), as well as a Harris score was 70. In the second case, a correction of 50° (82° vs. 132°) was achieved, with a Harris score of 68 points. Conclusions. Subtrochanteric osteotomy and intramedullary K-wire nailing are effective options for the treatment of coxa vara in patients with osteogenesis imperfecta

Risk factors for first weaning failure following mandibular distraction osteogenesis in pediatric patients with Pierre Robin sequence: a nested case-control study / 中华麻醉学杂志

Objective:To identify the risk factors for the first weaning failure following mandibular distraction osteogenesis in pediatric patients with Pierre Robin sequence (PRS).Methods:Clinical data of pediatric patients with PRS who underwent mandibular distraction osteogenesis from January 2018 to February 2023 were collected, including sex, age, premature birth, birth weight, surgical weight, cleft palate, syndrome type PRS, laryngeal/tracheobronchial malacia, simple congenital heart disease, complex congenital heart disease, preoperative mechanical ventilation, preoperative pulmonary infection, blood albumin concentration, difficulty in tracheal intubation under a visual laryngoscope, surgical duration, postoperative ventilator-associated pneumonia, duration of mechanical ventilation at first weaning, and traction length at first weaning. Children in whom the first postoperative machine withdrawal failed were included in observation group and matched to control cases(control group) in a 1∶4 ratio. The risk factors of which P values were less than 0.05 would enter the logistic regression analysis to stratify the risk factors for postoperative weaning failure. Results:There were significant differences in birth weight, cleft palate, duration of mechanical ventilation and traction length at first weaning, rate of combined cleft palate, preoperative pulmonary infection rate, rate of preoperative mechanical ventilation, and rate of postoperative ventilator-associated pneumonia between the two groups ( P<0.05). Binary logistic stepwise regression analysis showed that the preoperative mechanical ventilation ( OR=18.154, 95% CI 3.971-82.990, P<0.001) and postoperative ventilator-associated pneumonia ( OR=36.942, 95% CI 1.307-1043.985, P=0.034) were independent risk factors for first weaning failure after mandibular distraction osteogenesis, while birth weight gain ( OR=0.225, 95% CI 0.076-0.668, P=0.007) was a protective factor for first weaning failure ( P<0.05). Conclusions:Preoperative mechanical ventilation and postoperative ventilator-associated pneumonia are independent risk factors and birth weight gain is a protective factor for first weaning failure following mandibular distraction osteogenesis in pediatric patients with PRS.

Antibacterial copper sulfide/graphene oxide nanosheets composite film promotes angiogenic and osteogenic differentiation in vitro / 中华创伤骨科杂志

Objective:To investigate whether the antibacterial copper sulfide (CuS)/graphene oxide (GO) nanosheets composite film can promote angiogenesis and osteogenesis in vitro. Methods:GO and CuS/GO nanosheets were synthesized and mixed into polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC) hydrogel films. The study was conducted in 4 groups: PVA/CMC/GO, PVA/CMC/CuS/GO, PVA/CMC (only PVA/CMC-based film) and blank control (no material). The PVA/CMC, PVA/CMC/GO and PVA/CMC/CuS/GO films were characterized by electron scanning microscopy and energy dispersive spectrometer. The biocompatibility of different films (PVA/CMC/CuS/GO films with concentrations of CuS/GO nanotablets of 0, 50, 100, 200, 400, and 800 μ g/mL) was evaluated by CCK-8, live/dead cell staining, and hemolysis test. The angiogenesis was evaluated by cell migration and tube forming test in vitro. Alkaline phosphatase and alizarin red staining were used to evaluate osteogenesis in vitro, and the expression of osteogenic genes was measured by immunofluorescence staining and RT-qPCR. In addition, the bacterial plate counting method and bacteriostatic circle method were used to evaluate the antibacterial activity of films. Results:In the PVA/CMC/GO and PVA/CMC/CuS/GO groups, the surface of the PVA/CMC-based film was smooth and flat whereas the nanosheets composite films were irregularly flaky and convex. The biosafety experiments showed that the PVA/CMC-based film composited with GO or CuS/GO nanosheets at the concentration of 100 μg/mL had good biocompatibility. The results of angiogenesis in vitro showed that the migration ratio of HUVEC cells in the PVA/CMC/CuS/GO group was significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In the experiment of tube forming area and length, the PVA/CMC/CuS/GO group was significantly better than the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The osteogenic differentiation in vitro displayed that the alkaline phosphatase and alizarin red staining of MC3T3-E1 cells in the PVA/CMC/CuS/GO group were significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In addition, the fluorescence intensity of immunofluorescence staining in alkaline phosphatase and type Ⅰcollagen on MC3T3-E1 cells, and the mRNA expression levels of osteogenic related genes including alkaline phosphatase, bone morphogenetic protein 2, osteocalcin and osteopontin in the PVA/CMC/CuS/GO group were significantly higher than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The antibacterial assay showed that the PVA/CMC/CuS/GO group had a significantly greater antibacterial activity and a significantly larger inhibition zone against Gram-positive bacteria and Gram-negative bacteria than the PVA/CMC/GO, PVA/CMC and control groups ( P< 0.001). Conclusions:PVA/CMC films composited with GO or CuS/GO nanosheets demonstrate ideal biocompatibility and antibacterial properties which promote angiogenesis and osteogenic differentiation in vitro. In particular, antibacterial PVA/CMC/CuS/GO composite films with the coupling function of angiogenesis and osteogenesis are expected to provide a new strategy for infectious bone defects.

Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair (version 2023) / 中华创伤杂志

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

The role of E3 ubiquitin ligases in bone homeostasis and related diseases

The ubiquitin-proteasome system (UPS) dedicates to degrade intracellular proteins to modulate demic homeostasis and functions of organisms. These enzymatic cascades mark and modifies target proteins diversly through covalently binding ubiquitin molecules. In the UPS, E3 ubiquitin ligases are the crucial constituents by the advantage of recognizing and presenting proteins to proteasomes for proteolysis. As the major regulators of protein homeostasis, E3 ligases are indispensable to proper cell manners in diverse systems, and they are well described in physiological bone growth and bone metabolism. Pathologically, classic bone-related diseases such as metabolic bone diseases, arthritis, bone neoplasms and bone metastasis of the tumor, etc., were also depicted in a UPS-dependent manner. Therefore, skeletal system is versatilely regulated by UPS and it is worthy to summarize the underlying mechanism. Furthermore, based on the current status of treatment, normal or pathological osteogenesis and tumorigenesis elaborated in this review highlight the clinical significance of UPS research. As a strategy possibly remedies the limitations of UPS treatment, emerging PROTAC was described comprehensively to illustrate its potential in clinical application. Altogether, the purpose of this review aims to provide more evidence for exploiting novel therapeutic strategies based on UPS for bone associated diseases.

The airway management and treatment of newborns with micrognathia and laryngomalacia / 临床耳鼻咽喉头颈外科杂志

Objective:To explore the perioperative airway management and treatment of newborns with micrognathia and laryngomalacia. Methods:From January to December 2022, a total of 6 newborns with micrognathia and laryngomalacia were included. Preoperative laryngoscopy revealed concomitant laryngomalacia. These micrognathia were diagnosed as Pierre Robin sequences. All patients had grade Ⅱ or higher symptoms of laryngeal obstruction and required oxygen therapy or non-invasive ventilatory support. All patients underwent simultaneous laryngomalacia surgery and mandibular distraction osteogenesis. The shortened aryepiglottic folds were ablated using a low-temperature plasma radiofrequency during the operation. Tracheal intubation was maintained for 3-5 days postoperatively. Polysomnography（PSG） and airway CT examination were performed before and 3 months after the surgery. Results:Among the 6 patients, 4 required oxygen therapy preoperatively and 2 required non-invasiveventilatory support. The mean age of patients was 40 days at surgery. The inferior alveolar nerve bundle was not damaged during the operation, and there were no signs of mandibular branch injury such as facial asymmetry after the surgery. Laryngomalacia presented as mixed type: type Ⅱ+ type Ⅲ. The maximum mandibular distraction distance was 20 mm, the minimum was 12 mm, and the mean was 16 mm. The posterior airway space increased from a preoperative average of 3.5 mm to a postoperative average of 9.5 mm. The AHI decreased from a mean of 5.65 to 0.85, and the lowest oxygen saturation increased from a mean of 78% to 95%. All patients were successfully extubated after the surgery, and symptoms of laryngeal obstruction such as hypoxia and feeding difficulties disappeared. Conclusion:Newborns with micrognathia and laryngomalacia have multi-planar airway obstruction. Simultaneous laryngomalacia surgery and mandibular distraction osteogenesis are safe and feasible, and can effectively alleviate symptoms of laryngeal obstruction such as hypoxia and feeding difficulties, while significantly improving the appearance of micrognathia.