OBJECTIVE: To investigate the prenatal manifestation and genetic basis for two fetuses suspected for Osteocraniostenosis (OCS). METHODS: Two fetuses undergoing invasive prenatal diagnosis at Cangzhou People's Hospital in April and August 2021 for short long bones and abnormal skull morphology were selected as the study subjects. Clinical data were collected and analyzed. Genomic DNA was extracted from amniotic fluid and peripheral blood samples of the two couples. Candidate variants were validated by Sanger sequencing. Literature was retrieved from CNKI, Wanfang Data Knowledge Service Platform and PubMed using keywords including "FAM111A gene", "gracile bone dysplasia", "FAM111A" and "osteocraniostenosis" from January 1, 2000 to June 30, 2025. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: K2020-049). RESULTS: Fetus 1 was found to have short limbs, abnormal skull morphology and shallow cerebral sulci. Fetus 2 showed short limbs, irregular skull halo, prominent forehead and bilateral frontal narrowing. Trio-WES revealed that fetus 1 has carried a heterozygous missense variant c.1582G>C (p.Asp528His) in exon 4 of the FAM111A gene, which was unreported previously. Fetus 2 has harbored a heterozygous in-frame deletion c.1020_1022delTTC (p.Ser343del) in exon 6 of the FAM111A gene, which has been recorded as likely pathogenic by the ClinVar and HGMD databases. Sanger sequencing confirmed that the parents of both fetuses were wild-type for the variant sites. A total of 9 previously reported patients with FAM111A-related gracile bone dysplasia/OCS from 4 publications were retrieved. The main clinical features included intrauterine growth restriction, hypomineralized skull, gracile long bones with narrow medullary cavities and characteristic facial anomalies, which were in large in keeping with the prenatal features of the two fetuses. CONCLUSION Both fetuses were diagnosed with FAM111A-related OCS based on the characteristic prenatal findings and identification of the FAM111A variants. Above finding expanded the phenotypic spectrum of FAM111A-associated disorders and provided clues for the prenatal diagnosis and genetic counseling.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Phenotype ; Fetus ; Male ; Bone Diseases, Developmental/genetics* ; Adult

OBJECTIVE: To investigate the genetic etiology of a fetus diagnosed with Mandibulofacial dysostosis with microcephaly (MFDM). METHODS: A fetus that underwent prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, on May 19, 2025 was selected for analysis. Results of fetal ultrasound findings, chromosomal karyotyping, copy number variation sequencing (CNV-seq), and whole-exome sequencing (WES) were collected. Sanger sequencing was performed for familial validation of the pathogenic variant. The Human Protein Atlas (HPA), STRING, and Simple ClinVar databases were queried to characterize the biological features of the candidate gene. Three-dimensional structures of the wild-type and variant proteins were modeled and analyzed, and the evolutionary conservation of the affected amino acid was assessed using UGENE. Prenatal phenotypes associated with EFTUD2 variants were summarized through a review of the literature. This study was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Ethics No.: 2025-KY-029-01). RESULTS: At 23⁺² weeks of gestation, ultrasound examination revealed bilateral microtia with low-set ears, mild micrognathia with a reduced mandibular-facial angle, a single umbilical artery, a slightly narrow aortic diameter, and trivial mitral regurgitation. Amniotic fluid karyotyping and CNV-seq showed no abnormalities. WES identified a de novo, previously unreported EFTUD2 variant, c.698dupA (p.V235Gfs*27), in the fetus. This frameshift variant is predicted to alter the structural integrity of the EFTUD2 protein. Literature review indicated that micrognathia and microtia or low-set ears are the most common sonographic features in fetuses with EFTUD2 variants, while secondary findings may include abnormal stomach bubble, cleft palate, single umbilical artery, gastrointestinal atresia, polyhydramnios, and reduced aortic diameter. CONCLUSION The EFTUD2: c.698dupA (p.V235Gfs*27) variant is likely the genetic cause underlying MFDM in this fetus.
Humans ; Mandibulofacial Dysostosis/diagnostic imaging* ; Microcephaly/diagnostic imaging* ; Female ; Pregnancy ; Ribonucleoprotein, U5 Small Nuclear/chemistry* ; Peptide Elongation Factors/chemistry* ; Fetus ; DNA Copy Number Variations/genetics* ; Adult ; Ultrasonography, Prenatal

Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals ; Rats, Sprague-Dawley ; Rats ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Oxytocin/genetics* ; Receptors, Oxytocin/genetics* ; Humans ; Osteoporosis, Postmenopausal/genetics* ; Bone and Bones/drug effects* ; Brain/drug effects* ; Bone Marrow/drug effects*

This study investigates the therapeutic effect and underlying mechanism of Compound Ziyin Granules(CZYG) on postmenopausal osteoporosis(PMOP) induced by bilateral ovariectomy in rats. Six-month-old female SD rats were randomly divided into sham-operated(sham) group, ovariectomy(OVX) model group, high-, medium-, and low-dose CZYG groups, and alendronate sodium(AS) group. After 30 days of model establishment, treatment was administered by gavage once daily for 8 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of calcium ions, alkaline phosphatase(AKP), estrogen(E_2), osteoprotegerin(OPG), osteocalcin(BGP), tartrate-resistant acid phosphatase(TRAP), and type Ⅰ procollagen N-terminal propeptide(PINP). Hematoxylin-eosin(HE) staining was used to observe the histopathological changes in the femurs of rats, while micro-computed tomography(micro-CT) was used to analyze the microstructure of the distal femur. Western blot analysis was performed to measure the expression levels of bone metabolism-related proteins, including wingless-type MMTV integration site family member 2(Wnt2), β-catenin, low-density lipoprotein receptor-related protein 5(LRP5), glycogen synthase kinase-3β(GSK-3β). The mRNA expression levels of Wnt2, β-catenin, LRP5, GSK-3β, p-GSK-3β were determined by quantitative real-time PCR(qRT-PCR). Thirty days after bilateral ovariectomy, compared to the sham group, the OVX group showed significant increases in body weight and significant decreases in uterine coefficient. After 8 weeks of treatment, compared to the OVX group, CZYG(medium and high doses) and AS reduced body weight, with high-dose CZYG and AS significantly increasing the uterine coefficient. Serum levels of AKP and TRAP were significantly elevated, while levels of calcium, E_2, BGP, and OPG were significantly decreased in the OVX group. Compared to the OVX group, CZYG and AS significantly reduced serum levels of AKP and TRAP, while high-dose CZYG and AS notably increased the levels of E_2, BGP, OPG, and PINP. Micro-CT and HE staining results indicated that CZYG(medium and high doses) and AS significantly increased bone tissue volume, trabecular number, bone mineral density, and improved the microstructure of the femur. Compared to the OVX group, high-dose CZYG and AS significantly upregulated the protein and mRNA expression levels of Wnt2, β-catenin, and LRP5, and downregulated the phosphorylation level of p-GSK-3β. These results suggest that CZYG can improve PMOP by promoting estrogen secretion, improving bone metabolism indicators, increasing trabecular number and bone mineral density. Its mechanism may be related to the regulation of the Wnt/β-catenin signaling pathway.
Animals ; Female ; Rats, Sprague-Dawley ; Osteoporosis, Postmenopausal/genetics* ; Rats ; Wnt Signaling Pathway/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; beta Catenin/genetics* ; Osteoprotegerin/metabolism* ; Ovariectomy ; Calcium/blood* ; Bone Density/drug effects*

This study aims to investigate the therapeutic efficacy of 50 Hz-0.6 mT low-frequency pulsed electromagnetic field (PEMF) on postmenopausal osteoporosis in ovariectomized rats. Thirty 3-month-old female SD rats were selected and divided into a sham operation group (Sham), an ovariectomized model group (OVX), and a low-frequency pulsed electromagnetic field (PEMF) treatment group, with 10 rats in each group. After 8 weeks, the whole-body bone mineral density (BMD) of each group of rats was measured. The treatment group began to receive PEMF stimulation for 90 minutes daily, while the OVX group only received a simulated placement without electricity. After 6 weeks of intervention, all rats were sacrificed and tested for in vitro BMD, micro-CT, biomechanics, serum biochemical indicators, and bone tissue-related proteins. The results showed that the BMD of the OVX group was significantly lower than that of the Sham group 8 weeks after surgery, indicating successful modeling. After 6 weeks of treatment, compared with the OVX group, the PEMF group exhibited significantly increased BMD in the whole body, femur, and vertebral bodies. Micro-CT analysis results showed improved bone microstructure, significantly increased maximum load and bending strength of the femur, elevated levels of serum bone formation markers, and increased expression of osteogenic-related proteins. In conclusion, this study demonstrates that daily 90-minute exposure to 50 Hz-0.6 mT PEMF effectively enhances BMD, improves bone biomechanical properties, optimizes bone microstructure, stimulates bone formation, and inhibits bone resorption in ovariectomized rats, highlighting its therapeutic potential for postmenopausal osteoporosis.
Female ; Animals ; Rats, Sprague-Dawley ; Osteoporosis, Postmenopausal/therapy* ; Rats ; Bone Density ; Ovariectomy ; Magnetic Field Therapy/methods* ; Electromagnetic Fields

Aging involves the accumulation of various forms of molecular and cellular damage over time. Key features of aging, such as mitochondrial dysfunction, dysbiosis, and oxidative stress, are closely linked and largely driven by inflammation. This study examines the role of succinate, a key metabolite produced and utilized by cells of both host and microbes, and its receptor, succinate receptor 1 (SUCNR1), in age-related oral dysbiosis and inflammation. We examined young and aged wild-type (WT) and SUCNR1 knockout (KO) mice for this analysis. Our findings revealed significant aging-associated alveolar bone loss and succinate elevation in aged WT mice, along with notable changes in the oral microbiome. Conversely, aged KO mice showed reduced bone loss, lower succinate levels, less inflammation, and better-maintained microbial function. These results suggest that SUCNR1 is crucial in influencing aging-related succinate elevation, oral dysbiosis, and inflammation. Analysis of gene families and pathways in the oral microbiome demonstrated distinct aging-related changes between WT and KO mice, with the functional potential being preserved in the KO-aged group. This study underscores the importance of succinate elevation and signaling through SUCNR1 in regulating inflammation, alveolar bone loss, and shifts in the oral microbiome, offering potential targets for therapeutic interventions in age-related oral health issues.
Animals ; Dysbiosis/metabolism* ; Mice ; Succinic Acid/metabolism* ; Mice, Knockout ; Receptors, G-Protein-Coupled/metabolism* ; Inflammation/metabolism* ; Aging ; Alveolar Bone Loss/metabolism* ; Mouth/microbiology* ; Mice, Inbred C57BL ; Male ; Microbiota

Ankylosing spondylitis (AS) is linked to an increased prevalence of myocardial infarction (MI). However, research dedicated to elucidating the pathogenesis of AS-MI is lacking. In this study, we explored the biomarkers for enhancing the diagnostic and therapeutic efficiency of AS-MI. Datasets were obtained from the Gene Expression Omnibus database. We employed weighted gene co-expression network analysis and machine learning models to screen hub genes. A receiver operating characteristic curve and a nomogram were designed to assess diagnostic accuracy. Gene set enrichment analysis was conducted to reveal the potential function of hub genes. Immune infiltration analysis indicated the correlation between hub genes and the immune landscape. Subsequently, we performed single-cell analysis to identify the expression and subcellular localization of hub genes. We further constructed a transcription factor (TF)-microRNA (miRNA) regulatory network. Finally, drug prediction and molecular docking were performed. S100A12 and MCEMP1 were identified as hub genes, which were correlated with immune-related biological processes. They exhibited high diagnostic value and were predominantly expressed in myeloid cells. Furthermore, 24 TFs and 9 miRNA were associated with these hub genes. Enzastaurin, meglitinide, and nifedipine were predicted as potential therapeutic agents. Our study indicates that S100A12 and MCEMP1 exhibit significant potential as biomarkers and therapeutic targets for AS-MI, offering novel insights into the underlying etiology of this condition.
Humans ; Spondylitis, Ankylosing/complications* ; Systems Biology/methods* ; Myocardial Infarction/diagnosis* ; Biomarkers/metabolism* ; MicroRNAs/genetics* ; Gene Regulatory Networks ; Gene Expression Profiling ; Machine Learning

Postmenopausal osteoporosis (PMOP) is a systemic metabolic bone disease caused by the decrease in estrogen levels after menopause. It leads to bone loss, microstructural damage, and an increased risk of fractures. Studies have found that the gut microbiota and its metabolites can regulate bone metabolism through the gut-bone axis and the gut-brain axis. As research progresses, PMOP has been found to be associated with gut microbiota dysbiosis and Th17/Treg imbalance. The gut microbiota is closely related to the development and differentiation of Treg and Th17 cells. Among them, the metabolites of the gut microbiota such as short-chain fatty acids (SCFAs) can regulate the differentiation of effector T cells by acting on molecular receptors on immune cells, thereby regulating the bone immune process. The multifaceted relationship among the gut microbiota, SCFAs, Th17/Treg cell-mediated bone immunity, and bone metabolism is eliciting attention from researchers. Through a review of existing literature, we have comprehensively summarized the effects of the gut microbiota and SCFAs on PMOP, especially from the perspective of Th17/Treg balance. Regulating this balance may provide new opportunities for PMOP treatment.
Humans ; Gastrointestinal Microbiome/immunology* ; Fatty Acids, Volatile/metabolism* ; Osteoporosis, Postmenopausal/immunology* ; Female ; T-Lymphocytes, Regulatory/metabolism* ; Th17 Cells/metabolism* ; Dysbiosis/immunology* ; Bone and Bones/metabolism*

Muenke syndrome is an autosomal dominant genetic disorder that is typically characterized by unilateral or bilateral coronal synostosis, macrocephaly, midface hypoplasia, and developmental delays. This article reports a case of Muenke syndrome with a soft cleft palate. A heterozygous missense mutation c.749C>G (p.P250A) was identified in the FGFR3 gene through genetic testing. The patient exhibited typical features including coronal synostosis, bilateral hearing loss, right accessory auricle, and developmental delays and underwent surgery to repair the soft cleft palate. Cases of Muenke syndrome with cleft palate in the literature are relatively rare, and common associated symptoms include coronal suture craniosynostosis and hearing impairment. This article reports a differential diagnosis with other craniosynostosis syndromes and provides a reference for clinical diagnosis and treatment.
Humans ; Cleft Palate/surgery* ; Craniosynostoses/diagnosis* ; Mutation, Missense ; Palate, Soft/abnormalities* ; Receptor, Fibroblast Growth Factor, Type 3/genetics*

OBJECTIVES: This study aims to evaluate the short- to medium-term clinical efficacy of demineralized dentin matrix (DDM) particles applied during the immediate implantation of alveolar bone defects in the posterior region. METHODS: A total of 76 patients with 110 simple taper retentive implants were included in the conducted study and divided into Groups A and B in accordance with the bone grafting materials. Cone beam computed tomography and panoramic radiographs were taken immediately after implant surgery, immediate crown repair, and final follow-up time. The average follow-up time for Groups A and B was recorded. The primary observed clinical indicators were overall survival rate of the implant, bone resorption of the mesial and distal margins of the implant, buccal bone width resorption at the platform level and 1 mm below the platform, and bone height of the implant. Implant complication was a secondary observed clinical indicator. RESULTS: During the 1-to-5-year follow-up observation period, the mean follow-up of Group A was 38.2 months while that of Group B was 39.9 months. In Group A, two implants failed, one of which fractured, and implant overall survival rate was 96.4%. Four implants failed in Group B due to peri-implantitis, and implant overall survival rate was 92.6%. No statistically significant difference in implant overall survival rate was found between the two groups (P>0.05). In Group A, the average bone resorption in the mesial and distal margins of the implants was (1.011±2.047) mm and (0.841±2.183) mm, respectively. In Group B, the average bone resorption of the mesial and distal margins of the implants was (1.546±1.778) mm and (1.431±1.909) mm, respectively. No statistically significant difference was noted between the two groups (P>0.05). In Group A, buccal bone width resorption at the platform level and 1 mm below the platform of the implant was (0.782±2.084) mm and (0.681±2.307) mm, respectively. In Group B, buccal bone width resorption at the platform level and 1 mm below the platform of implant was (1.071±1.474) mm and (0.949±1.909) mm, respectively. No statistically significant difference was found between the two groups (P>0.05). In Group A, the buccal bone height of resorption of the implant was (1.044±2.214) mm. In Group B, the buccal bone height of resorption of the implant was (1.075±1.456) mm. No statistically significant difference in bone height was observed between the two groups (P>0.05). CONCLUSIONS During the 1-to-5-year follow-up observation period, DDM particles can effectively increase the height and width of alveolar bone, and they can achieve the same effect of maintaining alveolar bone contour and bone augmentation compared with deproteinized inorganic calf bone. DDM particles can be used as a potential new bone grafting material for the treatment of bone defects in clinical practice.
Humans ; Follow-Up Studies ; Dentin ; Cone-Beam Computed Tomography ; Dental Implants ; Male ; Female ; Adult ; Alveolar Bone Loss/surgery* ; Middle Aged ; Bone Transplantation ; Radiography, Panoramic ; Dental Implantation, Endosseous/methods* ; Immediate Dental Implant Loading