Pioneering a chick embryo model to explore the intrauterine etiology of developmental dysplasia of the hip in oligohydramnios conditions.

OBJECTIVE: To explore the impact of oligohydramnios on fetal movement and hip development, given its association with developmental dysplasia of the hip (DDH) but unclear mechanisms. METHODS: Chick embryos were divided into four groups based on the severity of oligohydramnios induced by amniotic fluid aspiration (control, 0.2 mL, 0.4 mL, 0.6 mL). Fetal movement was assessed by detection of movement and quantification of residual amniotic fluid volume. Hip joint development was assessed by gross anatomic analysis, micro-computed tomography (micro-CT) for cartilage assessment, and histologic observation at multiple time points. In addition, a subset of embryos from the 0.4 mL aspirated group underwent saline reinfusion and subsequent evaluation. RESULTS: Increasing volumes of aspirated amniotic fluid resulted in worsening of fetal movement restrictions (e.g., 0.4 mL aspirated and control group at E10: frequency difference -7.765 [95% CI: -9.125, -6.404]; amplitude difference -0.343 [95% CI: -0.588, -0.097]). The 0.4 mL aspirated group had significantly smaller hip measurements compared to controls, with reduced acetabular length (-0.418 [95% CI: -0.575, -0.261]) and width (-0.304 [95% CI: -0.491, -0.117]) at day E14.5. Histological analysis revealed a smaller femoral head (1.084 ±â€¯0.264 cm) and shallower acetabulum (0.380 ±â€¯0.106 cm) in the 0.4 mL group. Micro-CT showed cartilage matrix degeneration (13.6% [95% CI: 0.6%, 26.7%], P = 0.043 on E14.5). Saline reinfusion resulted in significant improvements in the femoral head to greater trochanter (0.578 [95% CI: 0.323, 0.833], P = 0.001). CONCLUSIONS: Oligohydramnios can cause DDH by restricting fetal movement and disrupting hip morphogenesis in a time-dependent manner. Timely reversal of oligohydramnios during the fetal period may prevent DDH.

Study on static and dynamic mechanical behavior of expansive soil modified by oyster shell powder.

To investigate the effect of oyster shell powder (OSP) on the static and dynamic properties of expansive soil, the mechanical properties of modified soil were obtained. Taking Ningming expansive soil as the research object, triaxial shear test, dynamic triaxial test and scanning electron microscope test were carried out on plain soil and 9 % expansive soil modified by oyster shell powder (ESMO). The results show that compared with plain soil, the effective cohesion of modified expansive soil with dosp < 1 mm (ESMO (dosp < 1 mm)) and dosp < 0.075 mm (ESMO (dosp < 0.075 mm)) is increased by 15.4 % and 32.8 %, respectively. Under cyclic loading, compared with plain soil, the plastic strain stability value of ESMO (dosp<0.075 mm) is reduced by 40.2 %, the pore water pressure stability value is reduced, and the stiffness is increased. The dynamic mechanical properties of ESMO (dosp<1 mm) showed the opposite trend. Through microscopic experimental analysis, the main reasons for this phenomenon are the particle size distribution, bonding form, and cementation of the two. The results can provide a theoretical basis for the practical application of ESMO and the establishment of constitutive model.

Does enhanced cognitive performance reduce fracture risk? a Mendelian randomization study.

OBJECTIVE: While observational studies have suggested a link between cognitive performance and fracture risk, the causality and site-specific nature are unclear. We applied Mendelian randomization (MR) to elucidate these associations. METHODS: 147 single-nucleotide polymorphisms (SNPs) tied strongly to cognitive performance (p< 5e-8) were selected. We performed MR analysis to investigate the causal relationship between cognitive performance and fractures at specific sites, including the wrist, upper arm, shoulder, ribs, sternum, thoracic spine, lumbar spine, pelvis, femur, leg, and ankle. The primary estimate was determined using the inverse variance-weighted method. Additionally, we examined heterogeneity using the MR Pleiotropy RESidual Sum Outlier test and Cochran Q, and employed MR-Egger regression to identify horizontal pleiotropy. RESULTS: MR analysis identified a causal association between cognitive performance and fractures at the lumbar-spine-pelvis (odds ratio [OR] = 0.727, 95% CI = 0.552-0.956, p = 0.023), and ribs-sternum-thoracic spine sites (OR = 0.774, 95% CI = 0.615-0.974, p = 0.029). However, no causal association was found for fractures at other sites. CONCLUSIONS: This study provided evidence of a causal connection between cognitive performance and fracture risk at certain locations. These findings underline the potential of cognitive enhancement strategies as innovative and effective methods for fracture prevention.

Causal Link between Gut Microbiota, Neurophysiological States, and Bone Diseases: A Comprehensive Mendelian Randomization Study.

Increasing evidence highlights a robust correlation between the gut microbiota and bone diseases; however, the existence of a causal relationship between them remains unclear. In this study, we thoroughly examined the correlation between gut microbiota and skeletal diseases using genome-wide association studies. Linkage disequilibrium score regression and Mendelian randomization were used to probe genetic causality. Furthermore, the potential mediating role of neuropsychological states (i.e., cognition, depression, and insomnia) between the gut microbiota and bone diseases was evaluated using mediation analysis, with genetic colocalization analysis revealing potential targets. These findings suggest a direct causal relationship between Ruminococcaceae and knee osteoarthritis (OA), which appears to be mediated by cognitive performance and insomnia. Similarly, a causal association was observed between Burkholderiales and lumbar pelvic fractures, mediated by cognitive performance. Colocalization analysis identified a shared causal variant (rs2352974) at the TRAF-interacting protein locus for cognitive ability and knee OA. This study provides compelling evidence that alterations in the gut microbiota can enhance cognitive ability, ameliorate insomnia, and potentially reduce the risk of site-specific fractures and OA. Therefore, strategies targeting gut microbiota optimization could serve as novel and effective preventive measures against fractures and OA.

Applications-oriented algicidal efficacy research and in-depth mechanism of a novel strain Brevibacillus sp. on Microcystis aeruginosa.

The utilization of algicidal bacteria for the control of harmful algal blooms (HABs) is a promising technology for ecological remediation. In our most recent publication, a novel strain of Brevibacillus sp. was isolated and proved to have significant algicidal activity and stability against Microcystis aeruginosa. In order to verify the algicidal effect of the strain in the practical application scenario, the algicidal efficacy of Brevibacillus sp. under conditions close to water in the environment was investigated. Results indicated that the algicidal threshold of Brevibacillus sp. culture was 3‰ inoculation concentration, and the removal rate of M. aeruginosa reached 100%. The process of Chl-a degradation followed a first-order kinetic model, which could be used to predict the degradation effect of M. aeruginosa in practical applications. Additionally, the inoculation of Brevibacillus sp. culture introduced additional nutrients, some of which remained in the water. Furthermore, the algicidal substances demonstrated good sustainability, with a removal rate of up to 78.53% at 144 h after three repeated uses. At 12 h, the algicidal substances caused a 78.65% increase in malondialdehyde (MDA) content in M. aeruginosa compared to the control group, thereby triggering the antioxidant system of M. aeruginosa. Moreover, algal cell fragments were observed to aggregate. This study provides a promising direction for treating cyanobacterial blooms using algicidal bacteria in practical applications.

The relation between radiographic manifestation and clinical characteristics of congenital radioulnar synostosis in children: A retrospective study from multiple centers.

Objective: To review the radiographic manifestation and clinical appearance of children with congenital radioulnar synostosis (CRUS) retrospectively. Study design: Retrospective cohort study of children with CRUS from multiple medical centers. Results: A total of 329 patients (male 259, female 70) with an average age of 5.4 years (0.5-16 years old), were included in this study. In particular, 145 patients (145/329, 44.1%) demonstrated bilateral involvement, and 184 patients (left 123, right 61) demonstrated unilateral involvement. As for Clear and Omery (C&O) classification, most patients belonged to Type III, and then followed by Type IV. As for Chinese Multi-center Pediatric Orthopedic Study Group (CMPOS) classification, most patients belonged to Type III, and then followed by Type II and Type I. In C&O Type III, 92.03% patients demonstrated severe pronation. According to CMPOS classification, 92.98% Type I patients demonstrated neutral to mild pronation, 72.17% Type II patients demonstrated moderate pronation, and 92.03% Type III patients demonstrated severe pronation. The age distribution showed no significant difference between C&O Type II and IV (P = 0.96); the pronation ankylosis severity showed no significant difference between C&O Type II and IV (P = 0.387). Conclusion: Although CRUS is a rare forearm deformity, there are certain relation between radiographic manifestation and clinical forearm functional restriction. CRUS patients of C&O or CMPOS Type III classification might suffer severe pronation deformity and warrant early intervention.

LncRNA-CASC15 knockdown inhibits the progression of esophageal squamous cell carcinoma through targeting miR-33a-5p/PTGS2 axis.

LncRNA CASC15 has been determined as a novel tumor-related lncRNA in many cancers. However, the in-detail role of CASC15 remains elusive in esophageal squamous cell carcinoma (ESCC). CASC15 expression level was detected in 113 ESCC tissues and paired adjacent normal tissues and in human ESCC cell lines. The effects of CASC15 on ESCC proliferation, migration, and invasion were assessed using CCK-8 and transwell assays. In addition, the potential downstream molecules of CASC15 were searched and confirmed by software algorithms, RT-qPCR, western blot, dual-luciferase reporter, and rescue experiments. CASC15 was upregulated in ESCC tissues and cell lines. CASC15 overexpression was associated with poorer prognosis in ESCC patients. Functionally, CASC15 knockdown inhibited cell proliferation, migration, and invasion of ESCC cells. Mechanistically, it was confirmed that CASC15 acts as competing endogenous RNA for miR-33a-5p to regulate PTGS2 expression. In addition, rescue assay showed that miR-33a-5p knockdown or PTGS2 overexpression abolished the cell proliferation, migration, and invasion inhibition role of CASC15 knockdown. In conclusion, this study indicates that CASC15 was upregulated in ESCC and CASC15 knockdown hindered ESCC progression through targeting the miR-33a-5p/PTGS2 axis. CASC15 might serve as a novel biomarker and therapeutic target for ESCC.

Retrospective Comparison of Outcomes Between Closed and Open Reduction for Developmental Dysplasia of the Hip in Children Aged 6-24 Months.

Purpose: We aimed to compare the outcomes between closed reduction (CR) and open reduction (OR) in children aged 6-24 months with developmental dysplasia of the hip (DDH) who could be reduced safely and stably by the closed reduction operation. Methods: We retrospectively reviewed the medical records of 77 patients who underwent CR or OR for DDH. Fifty-one patients (56 hips) underwent CR, 26 (29 hips) underwent OR. The demographic data, International Hip Dysplasia Institute classification and acetabular index (AI) before reduction and the centre-edge angle (CEA), AI, Alsberg angle (AA), Reimer's migration index (RMI), and height-to-width index (HWI) of the epiphysis were compared between two groups at the final follow-up. The percentage of coxa magna > 15% of the normal side and AA > 81° were calculated. Results: At the final follow-up, the mean AA in the CR and OR groups were 77.66° (60°-89°) and 81.97° (73°-91°) (p = 0.001), respectively, there were 32.14% and 58.62% of the hips with an AA > 81° (p = 0.019). The frequency of coxa magna > 15% of the normal side was higher in the OR group (60.9%) than in the CR group (6.5%) (p < 0.001). There was no difference in the improvement of AI, CEA, HWI, and RMI. Conclusion: In children aged 6-24 months with DDH, if a stable and safe CR can be obtained but with medial joint space up to 6mm, CR should be attempted first.

Polygonatum Polysaccharide Regulates Macrophage Polarization and Improves LPS-Induced Acute Lung Injury through TLR4-MAPK/NF-κB Pathway.

Objective: To investigate the effects of polygonatum sibiricum polysaccharides (PSPs) on the polarization of macrophages to M1 and M2 phenotypes and their potential mechanism. Methods: PSPs samples were prepared through water extraction and alcohol precipitation assay. The properties of PSPs were identified and analyzed by high-performance liquid chromatography, FT-IR, and NMR assay. Then, the effects of PSPs on mouse macrophage RAW264.7 viability were measured by CCK-8 assay. The cells were randomly divided into the control group, PSPs group, LPS group, and LPS + PSPs group. M1 phenotype polarization of RAW264.7 cells was induced by LPS treatment. The effects of various treatments on expression of M2 phenotype CD206, activation of TLR4-MAPK/NF-κB signal pathway, and translocation of NF-κB into the nucleus were determined by ELISA, western blot, and immunofluorescence assay, respectively. TLR4 inhibitor, TAK-242, and MAPK inhibitor, BIRB 796, were used to verify the effects of PSPs on the TLR4-MAPK/NF-κB pathway. The mice model of acute lung injury (ALI) was established and randomly divided into control group, PSPs group, LPS group, and LPS + PSPs group. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected to measure protein, inflammatory cells, neutrophil and macrophage cells number, and the levels of IL-6 and TNF-α in BALF. Flow cytometry and western blot assay measured the phenotypic changes of macrophages and the activation of the TLR4-MAPK/NF-κB signaling pathway. Results: The concentrations of PSPs lower than 100 µg/mL showed no toxicity to RAW264.7 cells. PSPs treatment could significantly reverse the reduction of CD206 protein expression (P < 0.05) and the increase of the expression of inflammatory factor TNF-α, IL-1ß, and IL-6 (all P < 0.05), TLR4-MAPK/NF-κB signaling pathway activation (all P < 0.05), and NF-κB translocation into the nucleus induced by LPS. The effect of inhibitors TAK-242 and BIRB 796 was consistent with that of PSPs. In the mice model of ALI, PSPs treatment could reduce the total protein levels of BALF and the number of inflammatory cells level, reverse the number changes of neutrophils and macrophages, and downregulate the proinflammatory factors IL-6 and TNF-α caused by LPS (all P < 0.05). In addition, PSPs treatment could also significantly reverse the increase in the number of iNOS expressing macrophages in alveolar lavage fluid induced by LPS (P < 0.05). In contrast, CD206-expressed cells decreased (P < 0.05). PSPs could also reverse LPS-induced TLR4-MAPK/NF-κB signal pathway protein activation (all P < 0.05). Conclusion: PSPs could suppress TLR4-MAPK/NF-κB activation induced by LPS, inhibit M1 phenotypic polarization of macrophages, and promote M2 phenotypic polarization, thus playing an anti-inflammatory role.

Fluoride increases the susceptibility of developmental dysplasia of the hip via increasing capsular laxity triggered by cell apoptosis and oxidative stress in vivo and in vitro.

The etiology of developmental dysplasia of the hip (DDH) is multifactorial, including breech presentation and hip capsular laxity. In particular, hip laxity is the main contributor to DDH by changing the ratio and distribution of collagens. Also, fluoride (F) affects collagens from various tissue besides bone and tooth. To investigate the association of DDH and excessive F intake, we conducted this research in lab on cell and animal model simultaneously. We established animal model of combination of DDH and F toxicity. The incidence of DDH in each group was calculated, and hip capsules were collected for testing histopathological and ultrastructural changes. The primary fibroblasts were further extracted from hip capsule and treated with F. The expression of collagen type I and III was both examined in vivo and in vitro, and the level of oxidative stress and apoptosis was also tested identically. We revealed that the incidence of DDH increased with F concentration. Furthermore, the oxidative stress and apoptosis levels of hip capsules and fibroblasts both increased after F exposure. Therefore, this study shows that excessive F intake increases susceptibility to DDH by altering hip capsular laxity in vivo and in vitro respectively. We believe that F might be a risk factor for DDH by increasing hip laxity induced by triggering fibroblast oxidative stress and apoptosis.

miR-129-2 upregulation induces apoptosis and promotes NSCLC chemosensitivity by targeting SOX4.

BACKGROUND: As one of the main causes of death worldwide, the treatment of non-small-cell lung cancer (NSCLC) is still unsatisfactory. This study aimed to explore the role of miR-129-2 in cell apoptosis and NSCLC chemosensitivity. METHODS: The effect of miR-129-2 on NSCLC was investigated using lung cancer cell lines (A549, NCl-H23, and HCC827), a normal lung cell line (BEAS-2B), and NSCLC tissues and adjacent healthy tissues. The oncogene SOX4 was verified as the target gene of miR-129-2 by luciferase reporter assay and real-time polymerase chain reaction. RESULTS: miR-129-2 expression was downregulated in NSCLC tissues, NCl-H23 cells, and A549 cells. miR-129-2 upregulation induced apoptosis in NCl-H23 and A549 cells. miR-129-2 upregulation also inhibited NSCLC in a xenograft mouse model, which was related to downregulation of SOX4 expression. Furthermore, miR-129-2 and SOX4 were aberrantly expressed in the cisplatin-resistant lung cancer cell line A549/DDP, and upregulation of miR-129-2 expression promoted cisplatin sensitivity in A549/DDP cells. CONCLUSIONS: In conclusion, miR-129-2 expression was downregulated in NSCLC tissues and cell lines, and its upregulation induced cell apoptosis and promoted NSCLC chemosensitivity by regulating SOX4. Therefore, miR-129-2 can serve as a potential diagnostic and therapeutic target in NSCLC.

Identification of an Immune-Related Gene Signature Associated with Prognosis and Tumor Microenvironment in Esophageal Cancer.

Background: Esophageal cancer (EC) is a common malignant tumor of the digestive system with high mortality and morbidity. Current evidence suggests that immune cells and molecules regulate the initiation and progression of EC. Accordingly, it is necessary to identify immune-related genes (IRGs) affecting the biological behaviors and microenvironmental characteristics of EC. Methods: Bioinformatics methods, including differential expression analysis, Cox regression, and immune infiltration prediction, were conducted using R software to analyze the Gene Expression Omnibus (GEO) dataset. The Cancer Genome Atlas (TCGA) cohort was used to validate the prognostic signature. Patients were stratified into high- and low-risk groups for further analyses, including functional enrichment, immune infiltration, checkpoint relevance, clinicopathological characteristics, and therapeutic sensitivity analyses. Results: A prognostic signature was established based on 21 IRGs (S100A7, S100A7A, LCN1, CR2, STAT4, GAST, ANGPTL5, TRAV39, F2RL2, PGLYRP3, KLRD1, TRIM36, PDGFA, SLPI, PCSK2, APLN, TICAM1, ITPR3, MAPK9, GATA4, and PLAU). Compared with high-risk patients, better overall survival rates and clinicopathological characteristics were found in low-risk patients. The areas under the curve of the two cohorts were 0.885 and 0.718, respectively. Higher proportions of resting CD4+ memory T lymphocytes, M2 macrophages, and resting dendritic cells and lower proportions of follicular helper T lymphocytes, plasma cells, and neutrophils were found in the high-risk tumors. Moreover, the high-risk group showed higher expression of CD44 and TNFSF4, lower expression of PDCD1 and CD40, and higher TIDE scores, suggesting they may respond poorly to immunotherapy. High-risk patients responded better to chemotherapeutic agents such as docetaxel, doxorubicin, and gemcitabine. Furthermore, IRGs associated with tumor progression, including PDGFA, ITPR3, SLPI, TICAM1, and GATA4, were identified. Conclusion: Our immune-related signature yielded reliable value in evaluating the prognosis, microenvironmental characteristics, and therapeutic sensitivity of EC and may help with the precise treatment of this patient population.

Management and effects of residual limbus inversion following closed reduction in developmental hip dysplasia: Protocol for a multicenter randomized controlled trial.

Closed reduction is a common treatment method for developmental dysplasia of the hip (DDH) in children aged 6-18 months. Residual acetabular dysplasia (RAD) is the most common complication associated with closed reduction. Residual limbus inversion (RLI) is a common condition following DDH closed reduction. Previously, we confirmed that when limbus inversion exceeds 32.2% of the acetabular depth after closed reduction, RLI persists and leads to RAD; however, this was based on a small cohort with a short-term follow-up period. The long-term fate of RLI and the correlation between RLI and RAD have yet to be verified. Therefore, this multicenter clinical study protocol was designed in three parts to investigate the effect of RLI on acetabular development after closed reduction of DDH (a multicenter retrospective cohort study), effect of RLI clearance on acetabular development (a multicenter retrospective and prospective randomized controlled study), and influence of inverted limbus clearance on acetabular development during DDH reduction (a multicenter prospective cohort study). Statistical analysis was performed by assessing the basic measures of acetabular development including the acetabular index and central-edge angle using frontal pelvic radiographs; the magnitude of limbus inversion, cartilaginous acetabular index, and T1ρ mapping values were measured using magnetic resonance imaging. The multicenter retrospective cohort studies required 5 years of follow-up period at minimum, and the prospective randomized controlled studies required reviews of frontal pelvic radiographs every 6 months as well as data pooling every 2 years to compare the short- and mid-term outcomes of hip joint morphological development between the two groups of pediatric patients. This research program is expected to verify that RLI following closed reduction of DDH can affect acetabular development and that limbus excision during DDH reduction can improve postoperative RAD. Therefore, the indication and timing of surgical intervention for RLI after closed reduction of DDH provide a basis for revising the acceptable criteria for utilizing closed reduction of DDH to reduce the incidence of osteoarthritis caused by RAD following DDH treatment. Clinical Trial: http://www.chictr.org.cn/showproj.aspx?proj=35045 (ChiCTR1900020996).

Monteggia type-I equivalent fracture in a fourteen-month-old child: A case report.

BACKGROUND: Monteggia and equivalent lesions are relatively rare but result in severe injuries in childhood, typically affecting children between 4 and 10 years old. The diagnosis and treatment of an equivalent Monteggia lesion is more complicated than those of a typical Monteggia fracture. This type of lesion may be challenging and may lead to serious complications if not treated properly. Pediatric Monteggia equivalent type I lesions have been reported in a few reports, all of which the patients were all over 4 years old. CASE SUMMARY: A 14-mo-old boy was referred to our clinic after falling from his bed 10 d prior. With regard to the clinical examination, an obvious swollen and angular deformity was noted on his right forearm. Plain radiographs and reconstructed computed tomography scans showed a Monteggia type I fracture and dislocation. Magnetic resonance imaging (MRI) confirmed a type I Monteggia equivalent lesion consisting of ulnar fracture and Salter-Harris type I injury in the proximal radius. The radial head was still in the joint, and only the radial metaphysis was displaced anteriorly. Open reduction and pinning of both displaced radial and ulnar fractures achieved an excellent result with full function. CONCLUSION: We recommend MRI examination or arthrography during reduction, especially if the secondary ossification center has not appeared.

The combined use of gamma-aminobutyric acid and walnut peptide enhances sleep in mice.

BACKGROUND: γ-aminobutyric acid (GABA) is a naturally occurring non-protein amino acid in the nervous system and has a wide range of physiological functions in the body. Walnut peptide (WP) contains high levels of arginine, aspartic acid, and glutamate, and has been shown to improve cognitive deficits and memory impairment in mice, while restoring antioxidant enzyme levels and reducing brain inflammatory mediators. METHODS: This study investigated the effects of GABA and WP, either alone or in combination, on sleep disturbances in mice. The pentobarbital-prolonged sleep test, pentobarbital-threshold sleep test, and barbital-induced sleep test were conducted to assess the effects of GABA and WP on sleep quality by gavage for 30 days as follows: GABA (102.25 mg/kg), WP (102.25 mg/kg), GABA (33.95, 102.25, 306.75 mg/kg)/WP (102.25 mg/kg) mixture. Furthermore, neurotransmitter tests were performed using mice brain tissue to investigate the possible mechanisms of GABA and WP on sleep status. RESULTS: The results showed that the combined use of GABA and WP significantly increased sleep duration compared with single administration of either WP or GABA. Increasing doses of GABA in mice treated with combined GABA and WP elevated the sleep rate to 50.00%, 64.28%, and 64.28%, respectively, compared to mice treated with GABA alone (35.71%) or mice treated with WP alone (28.57%). In mice that received a combination of GABA and WP orally, the latency time was significantly decreased after 30 days compared to control mice (P<0.05). Additionally, in mice treated with GABA, WP, or the combination of GABA and WP, the concentrations of GABA and acetylcholine (Ach) in the brain were significantly elevated and the concentration of serotonin (5-HT) was decreased compared to untreated mice. CONCLUSIONS: These results demonstrated that the combined administration of GABA and WP could prolong the sleep duration, increase sleep rate, and shorten the sleep latency more effectively than the administration of either GABA or WP alone. The mechanisms of action may be related to the regulation of neurotransmitters in the brain tissue by the combination of GABA and WP.

Replicative verification of susceptibility genes previously identified from families with segregating developmental dysplasia of the hip.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a complex hip joint deformity with effects ranging from acetabulum malformation to irreversible hip dislocation. Previous studies suggest a significant association of four variations, teneurin transmembrane protein 3 (TENM3, OMIM * 610083) (chr4:183721398), heparan sulfate proteoglycan 2 (HSPG2, OMIM * 142461) (chr1:22201470), ATPase plasma membrane Ca2+ transporting 4 (ATP2B4, OMIM * 108732) (chr1:203682345), and prostaglandin F receptor (PTGFR, OMIM * 600563) (chr1:79002214), with DDH susceptibility in families with segregating DDH. However, the association was not validated in sporadic cases and remains controversial. To confirm the association of the reported variations in these four genes with DDH, we conducted replicative verification in 250 sporadic samples with DDH from a Chinese Han population. METHODS: We conducted Sanger sequencing after amplifying the variation sites. The results were compared with the reference sequence from the GRCh37 assembly in UCSC ( http://genome.ucsc.edu ). RESULTS: Replication analysis of 250 sporadic samples by Sanger sequencing indicated that the four variations, TENM3 (OMIM * 610083, chr4:183721398), HSPG2 (OMIM * 142461, chr1:22201470), ATP2B4 (OMIM * 108732, chr1:203682345), and PTGFR (OMIM * 600563, chr1:79002214), were not associated with the susceptibility to DDH in the Chinese Han population. CONCLUSIONS: Further studies should be performed to identify other variations of these four genes that are potentially associated with DDH by whole-exome sequencing and the results should be verified in different populations.

Acetabular development and fate of inverted limbus in rabbits: Experimental observation from an animal model.

Using an animal model, we aimed to investigate the effects of an inverted limbus on acetabular development following closed reduction of developmental dysplasia of the hip (DDH). We interpositioned the menisci of 5-week-old rabbits (n = 40) into the hip joints to simulate limbus inversion following closed reduction for DDH. The acetabular index (AI) on anteroposterior pelvic radiographs and magnetic resonance imaging were used to evaluate acetabular development. Animals were euthanized at 4 and 8 weeks after surgery. Histological sections of the acetabular cartilage were stained and scored in accordance with the modified Mankin system. Scanning electron microscopy and transmission electron microscopy were used to examine the ultrastructure of the acetabular cartilage. Terminal deoxynucleotidyl transferase dUTP nick end-labeling staining was used to evaluate chondrocyte apoptosis. Immunohistochemistry and Western blot analyses were used to examine the expression of type X collagen (Col-X) and matrix metalloproteinase 13 (MMP-13) in the acetabular cartilage. AI values increased over a period and were higher in the experimental group than in the sham group. In the experimental group, the acetabular surface had become rough and had split in some cases. Chondrocytes within the acetabular cartilage had become hypertrophic, gradually forming clusters, and taking on an apoptotic appearance. Col-X and MMP-13 expression also increased with time. Our findings suggest that residual limbus inversion following closed reduction for DDH can cause progressive dysplasia of the acetabulum, apoptosis of acetabular chondrocytes, accelerated cartilage degeneration, and even early-stage osteoarthritis.

DDH in the Walking Age: Review of Patients with Long-Term Follow-Up.

INTRODUCTION: The best treatment option in children with late detected DDH is still a subject of much controversy and only few studies have investigated the long-term outcome of treatment in such patients. We performed a systematic review to assess long-term outcome of late detected DDH hips treated after walking age. METHODS: Studies met inclusion criteria if they: (1) reported at least 30 hips treated; (2) included children aged between 9 months and 12 years; (3) treatment indication was late detected DDH after walking age; (4) presented a minimum follow-up of 10 years; (5) reported a clinical or radiological outcome. The Kaplan-Meier method was used to evaluate long-term survival according to clinical and radiological outcomes. The rate of total hip replacement (THR) was retrieved. RESULTS: From a total of 6561 articles, 13 articles with grade IV level of evidence were included in our review. A total of 988 hips in 800 patients with a mean follow-up of 27.9 years (range 10-67) were included. The mean age at surgery was 3.3 years (range, 9 months-12 years). The rate of THR increased according to the length of final follow-up. In particular, all studies reported no case of THR at 23.5 years of follow-up, a rate of 10.2% of THR between 30 and 40 years of follow-up and a rate of 35.6% of THR in patients with follow-up more than 40 years. CONCLUSIONS: In patients with late detected DDH, most THR became necessary more than 30 years after the index procedure and their number increased further after 40 years and more of follow-up. Late detected DDH diagnosed after walking age is a life-long disease.

Prevalence and Risk Factors of Burnout Among Chinese Pediatric Orthopedic Surgeons.

BACKGROUND: Burnout is an occupational hazard among Chinese pediatric orthopedists, characterized by extreme physical and emotional exhaustion, and reduced professional efficacy; however, it has yet to be studied among this group of professionals in China. Our study aimed to assess the levels of burnout in Chinese pediatric orthopedists, and to identify the potential risk factors for burnout. METHODS: A 32-question, anonymous, cross-sectional survey was conducted from August to September 2019. Overall, 1392 Chinese pediatric orthopedists participated in the survey. RESULTS: Seven hundred valid questionnaires (50.3% response rate) were retrieved from 387 (55.3%) and 313 (44.7%) full-time and part-time pediatric orthopedists, respectively. Overall, 73.7% of the participants experienced burnout, of which 64.7% and 9.0% had some and severe burnout symptoms, respectively. The burnout levels significantly differed based on age (P=0.005), years in service (P=0.006), professional rank (P=0.03), weekly working hours (P<0.001), and monthly income (P=0.03). A binary logistic regression model showed that longer weekly working hours (adjusted odds ratio=1.29, 95% confidence interval: 1.09-1.52, P=0.004) was a risk factor for burnout, while higher monthly income (adjusted odds ratio=0.78, 95% confidence interval: 0.64 to 0.95, P=0.02) was protective against burnout, suggesting that younger pediatric orthopedists were more susceptible. No significant difference between full-time and part-time pediatric orthopedists or between sexes was detected in the adjusted analysis. CONCLUSIONS: Chinese pediatric orthopedists have a relatively high rate of burnout. Younger pediatric orthopedists have a greater chance of experiencing burnout. These results highlight the need for further policies, especially focused on younger pediatric orthopedists, to assist in better developing Chinese pediatric orthopedics. LEVEL OF EVIDENCE: Level: IV.