ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation.

Leptin protein was thought to be unique to leptin receptor (LepR), but the phenotypes of mice with mutation in LepR [db/db (diabetes)] and leptin [ob/ob (obese)] are not identical, and the cause remains unclear. Here, we show that db/db, but not ob/ob, mice had defect in tenotomy-induced heterotopic ossification (HO), implicating alternative ligand(s) for LepR might be involved. Ligand screening revealed that ANGPTL4 (angiopoietin-like protein 4), a stress and fasting-induced factor, was elicited from brown adipose tissue after tenotomy, bound to LepR on PRRX1+ mesenchymal cells at the HO site, thus promotes chondrogenesis and HO development. Disruption of LepR in PRRX1+ cells, or lineage ablation of LepR+ cells, or deletion of ANGPTL4 impeded chondrogenesis and HO in mice. Together, these findings identify ANGPTL4 as a ligand for LepR to regulate the formation of acquired HO.

Rheb1 is required for limb growth through regulating chondrogenesis in growth plate.

Ras homology enriched in the brain (Rheb) is well established as a critical regulator of cell proliferation and differentiation in response to growth factors and nutrients. However, the role of Rheb1 in limb development remains unknown. Here, we found that Rheb1 was dynamically expressed during the proliferation and differentiation of chondrocytes in the growth plate. Given that Prrx1+ limb-bud-like mesenchymal cells are the source of limb chondrocytes and are essential for endochondral ossification, we conditionally deleted Rheb1 using Prrx1-Cre and found a limb dwarfism in Prrx1-Cre; Rheb1fl/fl mice. Normalized to growth plate height, the conditional knockout (cKO) mice exhibited a significant decrease in column count of proliferative zones which was increased in hypertrophic zones resulting in decreased growth plate size, indicating abnormal endochondral ossification. Interestingly, although Rheb1 deletion profoundly inhibited the transcription factor Sox9 in limb cartilage; levels of runx2 and collagen type 2 were both increased. These novel findings highlight the essential role of Rheb1 in limb growth and indicate a complex regulation of Rheb1 in chondrocyte proliferation and differentiation.

First-Principles Calculations of TiB4 and TiB5 as Anodes with High Capacity for Na-Ion Batteries.

The electrochemical properties of TiB4 and TiB5 monolayers in Na-ion batteries (NIBs) were studied by using the first-principles calculation method based on density functional theory. The TiB4/TiB5 monolayer showed excellent Na storage capacity, capable of adsorbing two layers of Na with theoretical capacities of 1176.77 and 1052.05 mA g-1, respectively. The average operating voltages of the TiB4 and TiB5 monolayers are 0.073 and 0.042 eV, respectively, indicating that they can be used as anode materials for NIBs. More interestingly, the exposed B surface not only brings a high theoretical capacity but also provides a relatively small diffusion barrier of 0.16 (for TiB4) and 0.33 eV (for TiB5), enhancing their rate capability in NIBs.

Discrepancies in Sagittal Alignment of the Lower Extremity Among Different Brands of Robotic Total Knee Arthroplasty Systems.

BACKGROUND: There is an increasing number of different brands of robotic total knee arthroplasty (TKA) systems. Most robotic TKA systems share the same coronal alignment, while the definitions of sagittal alignment vary. The purpose of this study was to investigate whether these discrepancies impact the sagittal alignment of the lower extremity. METHODS: A total of 72 lower extremity computed tomography scans were included in our study, and 3-dimensional models were obtained using software. A total of 7 brands of robotic TKA systems were included in the study. The lower extremity axes were defined based on the surgical guide for each implant. We also set the intramedullary axis as a reference to evaluate the discrepancies in sagittal alignment of each brand of robotic system. RESULTS: On the femoral side, the axis definition was the same for all 7 robotic TKA systems. The robotic TKA axes showed a 2.41° (1.58°, 3.38°) deviation from the intramedullary axis. On the tibial side, the 7 robots had different axis definitions. The tibial mechanical axis of 6 of the TKA systems was more flexed than that of the intramedullary axis, which means the posterior tibial slope was decreased while the tibial mechanical axis of the remaining system was more extended. CONCLUSIONS: The sagittal alignment of the lower extremity for 7 different brands of robotic TKA systems differed from each other and all deviated from the intramedullary axis. Surgeons should be aware of this discrepancy when using different brands of robotic TKA systems to avoid unexpected sagittal alignment and corresponding adverse clinical outcomes. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

Influences of released humic acids during thermal hydrolysis on sludge anaerobic digestion: New insights from the molecular weight of humic acids.

Humic acids (HAs) would be excessively released during thermal hydrolysis pretreatment (THP) and deeply disturb anaerobic digestion (AD) of waste activated sludge (WAS). The molecular weights of HAs could affect HAs entering microbial cells, binding with digestive enzymes and participating in electron transfer, thereby determining its influences on sludge AD. Results in this study confirmed the different influences of HAs from diverse sources on sludge AD indeed had significant correlations with their molecular weights. The presence of commercial HAs (SAHA) inhibited methane production by 53.3% at 0.5 g/L while HAs extracted from raw sludge (WNHA) increased methane production by 20.5% at the same concentration, which attribute to the comprehensive impacts from their differences in functional group compositions and molecular weights. Moreover, comparing to WNHA, the HAs extracted from thermally hydrolyzed sludge (THHA) showed unchanged functional group compositions but reduced methane generation facilitation to 5.1%, which only be due to its decreased molecular weights. In-depth research indicated that HAs influences on enzymes were closely relative to its molecular weight. HAs with greater molecular weights presented more significant inhibition to extracellular enzymes while micromolecular HAs affected intracellular enzymes more. Furthermore, macromolecular HAs promoted sludge solubilization and acidification but hindered hydrolysis and methanogenesis, whereas micromolecular HAs promoted acidification but inhibited methanogenesis. This study underscored the importance of changes in molecular weight of HAs during sludge THP, offering insights into previous discrepancies in reports on HAs effects on sludge AD.

The Enhanced Performance of NiCuOOH/NiCu(OH)2 Electrode Using Pre-Conversion Treatment for the Electrochemical Oxidation of Ammonia.

Electrochemical oxidation of ammonia is an attractive process for wastewater treatment, hydrogen production, and ammonia fuel cells. However, the sluggish kinetics of the anode reaction has limited its applications, leading to a high demand for novel electrocatalysts. Herein, the electrode with the in situ growth of NiCu(OH)2 was partially transformed into the NiCuOOH phase by a pre-treatment using highly oxidative solutions. As revealed by SEM, XPS, and electrochemical analysis, such a strategy maintained the 3D structure, while inducing more active sites before the in situ generation of oxyhydroxide sites during the electrochemical reaction. The optimized NiCuOOH-1 sample exhibited the current density of 6.06 mA cm-2 at 0.5 V, which is 1.67 times higher than that of NiCu(OH)2 (3.63 mA cm-2). Moreover, the sample with a higher crystalline degree of the NiCuOOH phase exhibited lower performance, demonstrating the importance of a moderate treatment condition. In addition, the NiCuOOH-1 sample presented low selectivity (<20%) towards NO2- and stable activity during the long-term operation. The findings of this study would provide valuable insights into the development of transition metal electrocatalysts for ammonia oxidation.

Metabolic profile and transcriptome reveal the mystery of petal blotch formation in rose.

BACKGROUND: Petal blotch is a unique ornamental trait in angiosperm families, and blotch in rose petal is rare and has great esthetic value. However, the cause of the formation of petal blotch in rose is still unclear. The influence of key enzyme genes and regulatory genes in the pigment synthesis pathways needs to be explored and clarified. RESULTS: In this study, the rose cultivar 'Sunset Babylon Eyes' with rose-red to dark red blotch at the base of petal was selected as the experimental material. The HPLC-DAD and UPLC-TQ-MS analyses indicated that only cyanidin 3,5-O-diglucoside (Cy3G5G) contributed to the blotch pigmentation of 'Sunset Babylon Eyes', and the amounts of Cy3G5G varied at different developmental stages. Only flavonols but no flavone were found in blotch and non-blotch parts. As a consequence, kaempferol and its derivatives as well as quercetin and its derivatives may act as background colors during flower developmental stages. Despite of the differences in composition, the total content of carotenoids in blotch and non-blotch parts were similar, and carotenoids may just make the petals show a brighter color. Transcriptomic data, quantitative real-time PCR and promoter sequence analyses indicated that RC7G0058400 (F3'H), RC6G0470600 (DFR) and RC7G0212200 (ANS) may be the key enzyme genes for the early formation and color deepening of blotch at later stages. As for two transcription factor, RC7G0019000 (MYB) and RC1G0363600 (WRKY) may bind to the promoters of critical enzyme genes, or RC1G0363600 (WRKY) may bind to the promoter of RC7G0019000 (MYB) to activate the anthocyanin accumulation in blotch parts of 'Sunset Babylon Eyes'. CONCLUSIONS: Our findings provide a theoretical basis for the understanding of the chemical and molecular mechanism for the formation of petal blotch in rose.

Constructing high-accuracy theoretical Raman spectra of SARS-CoV-2 spike proteins based on a large fragment method.

In order to control COVID-19, rapid and accurate detection of the pathogenic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an urgent task. The target spike proteins of SARS-CoV-2 have been detected experimentally via Raman spectroscopy. However, there lacks high-accuracy theoretical Raman spectra of the spike proteins to as a standard reference for the clinic diagnostic purpose. In this paper, we propose a large fragment method to construct the high-precision Raman spectra for the spike proteins. The large fragment method not only reduces the calculation error but also improves the accuracy of the protein Raman spectra by completely calculating the interactions within the large fragment. The Pearson correlation coefficient of theoretical Raman spectra is greater than 0.929 or more. Compared with the experimental spectra, the characteristic patterns are easily visible. This work provides a detection standard for the spike proteins which shall bring a step closer to the fast recognition of SARS-CoV-2 via Raman spectroscopy method.

Exosomal miRNA profiling before and after surgery revealed potential diagnostic and prognostic markers for lung adenocarcinoma.

Exosome is a crucial manner for cancer cell to cell communication and circulating exosomes sever as promising diagnostic and prognostic markers for various types of diseases. A predominant type of cargo of exosome is small RNAs, especially miRNAs. Here, we profiled plasma exosomal miRNAs of six lung adenocarcinoma patients before and after surgery, as well as six healthy individuals as normal control. Our profiling revealed 38 upregulated and 37 downregulated exosomal miRNAs in the plasma of lung adenocarcinoma patients. Additionally, we found that most upregulated miRNAs were increased in the lung adenocarcinoma samples of TCGA database. We further evaluated the correlation between the upregulated exosomal miRNAs and overall survival with Kaplan-Meier survival analysis using online databases. Our results suggested that exosomal miR-151a-5p, miR-10b-5p, miR-192-5p, miR-106b-3p, and miR-484 are potential prognostic markers for lung adenocarcinoma. Importantly, we validated candidate miRNAs in lung adenocarcinoma patients before and after surgery as well as in healthy controls and found that miR-484 was significantly increased in the plasma of lung adenocarcinoma patients and strikingly decreased post-surgery. Hence, we provided novel information on lung adenocarcinoma-derived exosomal miRNA and potential non-invasive diagnostic and prognostic markers for lung adenocarcinoma.

The value of inflammation based prognostic scores in patients undergoing surgical resection for oesophageal and gastric carcinoma.

BACKGROUND AND OBJECTIVES: Surgical interventions for oesophagogastric cancer carry a significant burden of morbidity and mortality. A range of inflammation based prognostic scores have been proposed in an attempt to predict outcome. This study evaluated five such prognostic scores in oesophageal and gastric carcinoma patients. METHODS: The modified Glasgow Prognostic Score (mGPS), Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI), and Prognostic Nutrition Index (PNI) were calculated for 723 consecutive patients undergoing oesophagectomy or gastrectomy at a single center. The predictive accuracy of each score was assessed using ROC curves and survival analyses. RESULTS: Overall, only PLR and PNI were significantly predictive of patient survival (both P < 0.001), with no significant association detected for mGPS (P = 0.480), NLR (P = 0.210), or PI (P = 0.808). Subgroup analysis found the predictive accuracy of PNI to be significantly greater in oesophagectomy than gastrectomy patients (hazard ratio 2.75 vs 1.39, P = 0.016) and mGPS to be predictive of patient survival only in oesophagectomies (P < 0.001). CONCLUSIONS: Inflammation based prognostic scores may have a role in patients undergoing resection for oesophageal and gastric cancer. These scores are easily calculable from routinely collected data and could be used as an adjunct to existing staging modalities.

Evaluating the Public Health and Health Economic Impacts of Baloxavir Marboxil and Oseltamivir for Influenza Pandemic Control in China: A Cost-Effectiveness Analysis Using a Linked Dynamic Transmission-Economic Evaluation Model.

BACKGROUND: Pandemic influenza poses a recurring threat to public health. Antiviral drugs are vital in combating influenza pandemics. Baloxavir marboxil (BXM) is a novel agent that provides clinical and public health benefits in influenza treatment. METHODS: We constructed a linked dynamic transmission-economic evaluation model combining a modified susceptible-exposed-infected-recovered (SEIR) model and a decision tree model to evaluate the cost-effectiveness of adding BXM to oseltamivir in China's influenza pandemic scenario. The cost-effectiveness was evaluated for the general population from the Chinese healthcare system perspective, although the users of BXM and oseltamivir were influenza-infected persons. The SEIR model simulated the transmission dynamics, dividing the population into four compartments: susceptible, exposed, infected, and recovered, while the decision tree model assessed disease severity and costs. We utilized data from clinical trials and observational studies in the literature to parameterize the models. Costs were based on 2021 CN¥ and not discounted due to a short time-frame of one year in the model. One-way, two-way, and probabilistic sensitivity analyses were also conducted. RESULTS: The integrated model demonstrated that adding BXM to treatment choices reduced the cumulative incidence of infection from 49.49% to 43.26% and increased quality-adjusted life years (QALYs) by 0.00021 per person compared with oseltamivir alone in the base-case scenario. The intervention also amounted to a positive net monetary benefit of CN¥77.85 per person at the willingness to pay of CN¥80,976 per QALY. Sensitivity analysis confirmed the robustness of these findings, with consistent results across varied key parameters and assumptions. CONCLUSIONS: Adding BXM to treatment choices instead of only treating with oseltamivir for influenza pandemic control in China appears to be cost-effective compared with oseltamivir alone. The dual-agent strategy not only enhances population health outcomes and conserves resources, but also mitigates influenza transmission and alleviates healthcare burden.

Antibacterial photodynamic properties of silver nanoparticles-loaded curcumin composite material in chitosan-based films.

In order to cope with the increasingly severe food contamination and safety problems, a powerful sterilization of food packaging material is urgently needed. Chitosan (CS) has potential applications in food packaging due to its good film-forming properties, but its antibacterial activity is not sufficient to meet the needs in practical applications. Silver nanoparticles (AgNPs) have the problem of weak immediate antibacterial activity as a broad-spectrum antibacterial agent. Therefore, in this study, AgNPs@GA@Cur-POTS (AGCP) composite antibacterial system was prepared by combining AgNPs with antibacterial photodynamic therapy using gallic acid (GA) as a reducing agent, curcumin (Cur) as a photosensitizer and perfluorosilane (POTS) for surface modification. The results showed that AGCP could produce a large number of reactive oxygen species under blue light irradiation, killing >90 % of E. coli and S. aureus within 2 h. Subsequently, the composite film of CS loaded with AGCP (CS/AGCP) was prepared by the flow-delay method. The CS/AGCP composite film exhibited excellent barrier properties and antioxidant activity, while its antibacterial rates against E. coli and S. aureus reached 98.44 ± 1.27 % and 99.11 ± 0.24 %, respectively, while the OD630 values of the two groups of bacteria treated with it showed no significant increase in incubation for up to 132 h, exhibiting remarkable and sustained antibacterial effects. Taken together, this work will provide a new strategy for antibacterial food packaging.

Combining Multiple Omics with Molecular Dynamics Reveals SCP2-Mediated Cytotoxicity Effects of Aflatoxin B1 in SW480 Cells.

Aflatoxins belong to a class of mycotoxins, among which aflatoxin B1 (AFB1) has detrimental effects on the health of both animals and humans. It is associated with long-term exposure-induced carcinogenicity, hepatotoxicity, renal toxicity, neurotoxicity, and immunosuppressive properties, resulting in a variety of diseases. The intestine is the first barrier for human exposure to AFB1, but limited investigations have been conducted to clarify the underlying mechanisms of intestinal cytotoxicity. The mechanism of AFB1-induced cytotoxicity was investigated in this study using an integrated approach combining transcriptome, proteome, and metabolome analysis along with molecular dynamics simulation. After exposing SW480 cells to 50 µM AFB1 for 72 h, the transcriptome, proteome, and metabolome exhibited significant enrichment in pathways associated with oxidative stress, fatty acid and lipid metabolism, and glutathione metabolism. The experimental results demonstrated that AFB1 significantly reduces SW480 cells viability, and induces oxidative stress, calcium overload, mitochondrial damage, and lipid metabolism disorders.

Integrating Epigenetics, Proteomics, and Metabolomics to Reveal the Involvement of Wnt/ß-Catenin Signaling Pathway in Oridonin-Induced Reproductive Toxicity.

Oridonin is the primary active component in the traditional Chinese medicine Rabdosia rubescens, displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed in clinical therapy for acute and chronic pharyngitis, tonsillitis, as well as bronchitis. Nevertheless, the clinical application of oridonin is significantly restricted due to its reproductive toxicity, with the exact mechanism remaining unclear. The aim of this study was to investigate the mechanism of oridonin-induced damage to HTR-8/SVneo cells. Through the integration of epigenetics, proteomics, and metabolomics methodologies, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, ß-catenin, CLDN1, CCND1, and ZO-1 protein levels. This implied that the inhibition of the Wnt/ß-catenin signaling pathway and disruption of tight junction might be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8/SVneo cells.

Physicochemical and Rheological Properties of Degraded Konjac Gum by Abalone (Haliotis discus hannai) Viscera Enzyme.

In the present study, a new degraded konjac glucomannan (DKGM) was prepared using a crude enzyme from abalone (Haliotis discus hannai) viscera, and its physicochemical properties were investigated. After enzymatic hydrolysis, the viscosity of KGM obviously decreased from 15,500 mPa·s to 398 mPa·s. The rheological properties analysis of KGM and DKGMs revealed that they were pseudoplastic fluids, and pseudoplasticity, viscoelasticity, melting temperature, and gelling temperature significantly decreased after enzymatic hydrolysis, especially for KGM-180 and KGM-240. In addition, the molecular weight of KGM decreased from 1.80 × 106 Da, to 0.45 × 106 Da and the polydispersity index increased from 1.17 to 1.83 after 240 min of degradation time. Compared with natural KGM, the smaller particle size distribution of DKGM further suggests enzyme hydrolysis reduces the aggregation of molecular chains with low molecular weight. FT-IR and FESEM analyses showed that the fragmented KMG chain did not affect the structural characteristics of molecular monomers; however, the dense three-dimensional network microstructure formed by intermolecular interaction changed to fragment microstructure after enzyme hydrolysis. These results revealed that the viscosity and rheological properties of KGM could be controlled and effectively changed using crude enzymes from abalone viscera. This work provides theoretical guidance for the promising application of DKGM in the food industry.

Comprehensive Profiling of Transcriptome and m6A Epitranscriptome Uncovers the Neurotoxic Effects of Yunaconitine on HT22 Cells.

Objective: To explore different mRNA transcriptome patterns and RNA N6-methyladenosine (m6A) alteration in yunaconitine (YA)-treated HT22 mouse hippocampal neuron, and uncover the role of abnormal mRNA expression and RNA m6A modification in YA-induced neurotoxicity. Methods: HT22 cells were treated with 0, 5, 10, and 50 µM of YA for 72 h to evaluate their viability and GSH content. Subsequently, mRNA-seq and MeRIP-seq analyses were performed on HT22 cells treated with 0 and 10 µM YA for 72 h, and molecular docking was used to simulate interactions between YA and differentially expressed m6A regulators. The mitochondrial membrane potential was examined using the JC-10 probe, and RT-qPCR was conducted to verify the expression levels of differentially expressed m6A regulatory factors, as well as to assess alterations in the mRNA expression levels of antioxidant genes. Results: YA treatment significantly reduced the viability of HT22 cells and decreased GSH content. The mRNA-seq analysis obtained 1018 differentially expressed genes, KEGG and GO enrichment results of differentially expressed genes mainly comprise the nervous system development, cholinergic synapse, response to oxidative stress, and mitochondrial inner membrane. A total of 7 differentially expressed m6A regulators were identified by MeRIP-seq. Notably, molecular docking results suggested a stable interaction between YA and most of the differentially expressed m6A regulators. Conclusion: This study showed that YA-induced HT22 cell damage was associated with the increased methylation modification level of target gene m6A and abnormal expression of m6A regulators.

Preparation of sodium alginate modified silver-metal organic framework and application in citric acid/PVA antimicrobial packaging.

Silver-metal organic framework (Ag@MOF) has exhibited outstanding antimicrobial activity in antimicrobial applications, and reducing the biotoxicity associated with silver has become a research priority. In this study, Ag@MOF was initially modified with sodium alginate (SA) to form SA-Ag@MOF. The results showed that SA could control the release of Ag+, reducing the release by about 8% at 24 h, and the biotoxicity was significantly reduced. Finally, SA-Ag@MOF was applied as an antimicrobial agent in citric acid-modified PVA film to develop a novel composite antimicrobial film. When added at 2 MIC, the CA3-M2 film can effectively inhibit the growth of E. coli and S. aureus, and the inhibition rate has reached 98%. For white radish packaging applications, CA3-M2 film inhibited the growth of surface microorganisms, while ensuring moisture and tissue hardness to extend shelf-life up to 7 days. Overall, the strategy conceived here can be a theoretical basis for novel antimicrobial packaging.

Long-term prognosis in patients with thymoma combined with myasthenia gravis: a propensity score-matching analysis.

Introduction: We aimed to assess the impact of myasthenia gravis (MG) on the long-term prognosis in patients with thymoma after surgery and identify related prognostic factors or predictors. Methods: This retrospective observational study included 509 patients with thymoma (thymoma combined with MG [MG group] and thymoma alone [non-MG group]). Propensity score matching was performed to obtain comparable subsets of 96 patients in each group. A comparative analysis was conducted on various parameters. Results: Before matching, the 10-year survival and recurrence-free survival rates in both groups were 93.8 and 98.4%, and 85.9 and 93.4%, respectively, with no statistically significant difference observed in the survival curves between the groups (p > 0.05). After propensity score matching, 96 matched pairs of patients from both groups were created. The 10-year survival and recurrence-free survival rates in these matched pairs were 96.9 and 97.7%, and 86.9 and 91.1%, respectively, with no statistical significance in the survival curves between the groups (p > 0.05). Univariate analysis of patients with thymoma postoperatively revealed that the World Health Organization histopathological classification, Masaoka-Koga stage, Tumor Node Metastasis stage, resection status, and postoperative adjuvant therapy were potentially associated with tumor recurrence after thymoma surgery. Multivariate analysis demonstrated that the Masaoka-Koga stage and postoperative adjuvant therapy independently predicted the risk of recurrence in patients with thymoma after surgery. Conclusion: There was no difference in prognosis in patients with thymoma with or without MG. The Masaoka-Koga stage has emerged as an independent prognostic factor affecting recurrence-free survival in patients with thymoma, while postoperative adjuvant therapy represents a poor prognostic factor.

Developmental dysplasia of the hip: A systematic review of susceptibility genes and epigenetics.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a complex developmental deformity whose pathogenesis and susceptibility-related genes have yet to be elucidated. This systematic review summarizes the current literature on DDH-related gene mutations, animal model experiments, and epigenetic changes in DDH. METHODS: We performed a comprehensive search of relevant documents in the Medline, Scopus, Cochrane, and ScienceDirect databases covering the period from October 1991 to October 2021. We analyzed basic information on the included studies and summarized the DDH-related mutation sites, animal model experiments, and epigenetic changes associated with DDH. RESULTS: A total of 63 studies were included in the analysis, of which 54 dealt with the detection of gene mutations, 7 presented details of animal experiments, and 6 were epigenetic studies. No genetic mutations were clearly related to the pathogenesis of DDH, including the most frequently studied genes on chromosomes 1, 17, and 20. Most gene-related studies were performed in Han Chinese or North American populations, and the quality of these studies was medium or low. GDF5 was examined in the greatest number of studies, and mutation sites with odds ratios > 10 were located on chromosomes 3, 9, and 13. Six mutations were found in animal experiments (i.e., CX3CR1, GDF5, PAPPA2, TENM3, UFSP2, and WISP3). Epigenetics research on DDH has focused on GDF5 promoter methylation, three microRNAs (miRNAs), and long noncoding RNAs. In addition, there was also a genetic test for miRNA and mRNA sequencing. CONCLUSIONS: DDH is a complex joint deformity with a considerable genetic component whose early diagnosis is significant for preventing disease. At present, no genes clearly involved in the pathogenesis of DDH have been identified. Research on mutations associated with this condition is progressing in the direction of in vivo experiments in animal models to identify DDH susceptibility genes and epigenetics analyses to provide novel insights into its pathogenesis. In the future, genetic profiling may improve matters.

Undetected Intraoperative Periprosthetic Femoral Fractures in Patients Undergoing Primary Total Hip Arthroplasty: A Retrospective Case Series and Literature Review.

OBJECTIVE: Periprosthetic fracture in total hip arthroplasty (THA) can be catastrophic, and early detection and appropriate management are vital to the overall prognosis. This study aimed to describe and summarize the features of undetected intraoperative periprosthetic femoral fractures (IPFFs) in primary THA patients and treatment measures and to review the relevant literature. METHODS: We reviewed a total of 6350 primary THAs performed at our institution between January 2013 and December 2020 and screened all IPFFs. Of 138 IPFFs, 24 were undetected and met the inclusion criteria. We recorded and compared basic patient and operative information and measured some parameters to evaluate canal morphologies based on preoperative radiographs. We also compared fracture line characteristics using postoperative radiographs to summarize the features of intraoperative fractures and propose treatment strategies. The Kolmogorov-Smirnov test was used to test the normality of the variable distributions. Measured parameters in all groups were analyzed using one-way analysis of variance and compared using Dunnett's test. The χ2 and Fisher exact tests were used to compare reoperation rates across the groups. Interrater and intrarater reliability were evaluated by intraclass correlation coefficients. RESULTS: Among the 24 hips, there was no significant difference in patient demographics, basic operative information or morphology. The incidence of IPFFs in primary THA patients was 2.17%, and up to 17.4% of IPFFs were undetected until postoperative fluoroscopy. The incidence of undetected IPFFs among all primary THA patients was 0.38% and varied by stem type, with the highest incidence in femurs with either anatomical (1.04%, 4/385) or modular stems (0.90%, 9/1003). Femurs with anatomical stems had a higher reoperation rate. The distal periprosthetic (Gruen zone 4) fracture line of femurs with tapered stems was more prone to involve the medial or lateral bone cortex, which could cause instability. CONCLUSION: An undetected IPFF is most likely in femurs fitted with a prosthesis of an inappropriate size or type. Anatomical stems will most likely cause unstable fractures; thus, it is recommended to use them with caution and note the possibility of medial distal femoral fracture. Improper modular stem type or size selection results in longitudinal fractures of the distal femur, and prophylactic cerclage wire binding is recommended in dysplastic hips. Incorrect use of tapered stems in well-ossified femurs may cause distal femoral fractures involving the medial or lateral bone cortex. Intraoperative fluoroscopy after implantation may help detect hidden fractures.