Identification of a fatty acid metabolism-related gene signature to predict prognosis in stomach adenocarcinoma.

BACKGROUND: Fatty acid metabolism (FAM) contributes to tumorigenesis and tumor development, but the role of FAM in the progression of stomach adenocarcinoma (STAD) has not been comprehensively clarified. METHODS: The expression data and clinical follow-up information were obtained from The Cancer Genome Atlas (TCGA). FAM pathway was analyzed by gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) methods. Univariate Cox regression analysis was conducted to select prognosis genes. Molecular subtypes were classified by consensus clustering analysis. Furthermore, least absolute shrinkage and selection operator (Lasso) analysis was employed to develop a risk model. ESTIMATE and tumour immune dysfunction and exclusion (TIDE) algorithm were used to assess immunity. pRRophetic package was conducted to predict drug sensitivity. RESULTS: Based on 14 FAM related prognosis genes (FAMRG), 2 clusters were determined. Patients in C2 showed a worse overall survival (OS). Furthermore, a 7-FAMRG risk model was established as an independent predictor for STAD, with a higher riskscore indicating an unfavorable OS. High riskscore patients had higher TIDE score and these patients were more sensitive to anticancer drugs such as Bortezomib, Dasatinib and Pazopanib. A nomogram based on riskscore was an effective prediction tool applicable to clinical settings. The results from pan-cancer analysis supported a prominent application value of riskscore model in other cancer types. CONCLUSION: The FAMRGs model established in this study could help predict STAD prognosis and offer new directions for future studies on dysfunctional FAM-induced damage and anti-tumor drugs in STAD disease.

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.

Nicotinamide adenine dinucleotide treatment confers resistance to neonatal ischemia and hypoxia: effects on neurobehavioral phenotypes.

JOURNAL/nrgr/04.03/01300535-202412000-00031/figure1/v/2024-04-08T165401Z/r/image-tiff Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy. Currently, there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury. Here, we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide, which can protect against hypoxic injury in adulthood, in a mouse model of neonatal hypoxic-ischemic brain injury. In this study, nicotinamide adenine dinucleotide (5 mg/kg) was intraperitoneally administered 30 minutes before surgery and every 24 hours thereafter. The results showed that nicotinamide adenine dinucleotide treatment improved body weight, brain structure, adenosine triphosphate levels, oxidative damage, neurobehavioral test outcomes, and seizure threshold in experimental mice. Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice. Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine (or cysteine) peptidase inhibitor, clade A, member 3N, fibronectin 1, 5'-nucleotidase, cytosolic IA, microtubule associated protein 2, and complexin 2. Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways (e.g., nuclear factor-kappa B, mitogen-activated protein kinase, and phosphatidylinositol 3 kinase/protein kinase B). These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

Are Generative Pretrained Transformer 4 Responses to Developmental Dysplasia of the Hip Clinical Scenarios Universal? An International Review.

OBJECTIVE: There is increasing interest in applying artificial intelligence chatbots like generative pretrained transformer 4 (GPT-4) in the medical field. This study aimed to explore the universality of GPT-4 responses to simulated clinical scenarios of developmental dysplasia of the hip (DDH) across diverse global settings. METHODS: Seventeen international experts with more than 15 years of experience in pediatric orthopaedics were selected for the evaluation panel. Eight simulated DDH clinical scenarios were created, covering 4 key areas: (1) initial evaluation and diagnosis, (2) initial examination and treatment, (3) nursing care and follow-up, and (4) prognosis and rehabilitation planning. Each scenario was completed independently in a new GPT-4 session. Interrater reliability was assessed using Fleiss kappa, and the quality, relevance, and applicability of GPT-4 responses were analyzed using median scores and interquartile ranges. Following scoring, experts met in ZOOM sessions to generate Regional Consensus Assessment Scores, which were intended to represent a consistent regional assessment of the use of the GPT-4 in pediatric orthopaedic care. RESULTS: GPT-4's responses to the 8 clinical DDH scenarios received performance scores ranging from 44.3% to 98.9% of the 88-point maximum. The Fleiss kappa statistic of 0.113 (P = 0.001) indicated low agreement among experts in their ratings. When assessing the responses' quality, relevance, and applicability, the median scores were 3, with interquartile ranges of 3 to 4, 3 to 4, and 2 to 3, respectively. Significant differences were noted in the prognosis and rehabilitation domain scores (P < 0.05 for all). Regional consensus scores were 75 for Africa, 74 for Asia, 73 for India, 80 for Europe, and 65 for North America, with the Kruskal-Wallis test highlighting significant disparities between these regions (P = 0.034). CONCLUSIONS: This study demonstrates the promise of GPT-4 in pediatric orthopaedic care, particularly in supporting preliminary DDH assessments and guiding treatment strategies for specialist care. However, effective integration of GPT-4 into clinical practice will require adaptation to specific regional health care contexts, highlighting the importance of a nuanced approach to health technology adaptation. LEVEL OF EVIDENCE: Level IV.

The influence of simulated weightlessness on the composition and function of gut microbiota and bile acid metabolism products.

The aim of this study was to investigate the effects of simulated weightlessness on gut microbiota, bile acid metabolism, and inflammatory cytokines compared to the control group. The study compared the changes in gut microbiota at the phylum and genus levels in the feces of control and weightlessness rats after 1 and 8 weeks using fecal 16S rRNA sequencing. In the weightlessness group, there was an increase in the proportion of anaerobic bacteria and biofilm-forming bacteria, and a decrease in the proportion of aerobic and Gram-negative bacteria. Further investigations explored the impact of weightlessness on bile acid metabolism products. The levels of glycine ursodeoxycholic acid, glycine chenodeoxycholic acid, glycine deoxycholic acid and glycine cholic acid levels were lower in rats undergoing weightlessness for 1 week compared to the control group.Moreover, the study examined the relationship between gut microbiota and bile acid metabolism products.It was observed that, unlike the control group, there were significant positive correlations between Planctomycetes, Proteobacteria, Synergistetes, and GUDCA levels in rats after 1 week of weightlessness. Finally, ELISA results indicated significant differences in the levels of MDA, GSH, NLRP3, and SIgA inflammatory cytokines between rats undergoing weightlessness for 1 week and the control group rats. Our research confirmed that the simulated weightlessness environment significantly affects the gut microbiota and bile acid metabolism in rats, potentially leading to changes in inflammatory cytokines and causing intestinal tissue inflammation. Further exploring the relationship between gut microbiota and bile acid metabolism under weightless conditions will be crucial for understanding the functional changes in the intestines caused by weightlessness.

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.

Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter.

The aim of this study was to explore the changes in pH and pepsin concentrations in oral lavage fluid of rabbit reflux model. A total of 18 New Zealand rabbits were randomly divided into two groups. The lower esophageal sphincters (LESs) of the rabbits in the experimental group (EG) were dilated by balloon after the LESs were localized by manometry. The pH levels of the throat and the lower esophagus were monitored 1 week before and 2 weeks after inflation. Oral lavage fluid was collected 1 week before, and 2 and 8 weeks after inflation. The pH monitoring showed that the percentage of reflux time, the number of reflux events, and the longest time of reflux after the dilation (AE) in the EG were significantly higher than before the dilation (P < 0.01). The pepsin concentrations at 2 and 8 weeks AE in the EG were significantly higher than that before and that in the control group (P < 0.05). Based on receiver operating characteristic curve analysis, the best diagnostic threshold value was 30.3 ng/ml. The reflux model constructed by balloon inflation of the LES in rabbits is characterized by a decrease in throat pH and an increase in salivary pepsin concentration.

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.

Medium-term clinical efficacy of endoscopic antireflux mucosectomy on laryngopharyngeal reflux: a retrospective multicenter cohort study.

BACKGROUND AND AIMS: Studies on the effect of antireflux mucosectomy (ARMS) on laryngopharyngeal reflux disease (LPRD) are lacking. We conducted a multicenter retrospective study to explore the clinical efficacy of ARMS on LPRD. METHODS: We retrospectively analyzed the data of patients diagnosed with LPRD by oropharyngeal 24-hour Dx-pH monitoring who underwent ARMS. The effects of ARMS on LPRD were evaluated by comparing the 36-Item Short-Form Survey (SF-36), reflux symptom index (RSI), and 24-hour Dx-pH monitoring scores before and 1 year after surgery. Patients were divided into groups according to gastroesophageal flap valve (GEFV) grade to explore the effect of GEFV on prognosis. RESULTS: One hundred eighty-three patients were included in the study. The oropharyngeal pH monitoring results showed that the effective rate of ARMS was 72.1% (132/183). After surgery, the SF-36 score was higher (P = .000), RSI score was lower (P = .000), and the symptoms of constant throat clearing; difficulty swallowing food, liquids, and pills; coughing after eating or after lying down; troublesome or annoying cough; and breathing difficulties or choking episodes were significantly improved (P < .05). Upright reflux was dominant in GEFV grade I to III patients, and the SF-36, RSI, and upright Ryan index scores were significantly improved after surgery (P < .05). In GEFV grade IV patients, regurgitation was dominant in the supine position, and the above evaluation indexes were worse after surgery (P < .05). CONCLUSIONS: ARMS is effective for LPRD. The GEFV grade can predict the prognosis of surgery. ARMS is effective in GEFV grade I to III patients, but the effect is not exact in GEFV grade IV patients and may even be aggravated.

A Comparison Between W Score and RYAN Score in Diagnosing Laryngopharyngeal Reflux Disease.

OBJECTIVE: To assess the diagnostic value of the W score in differentiating laryngopharyngeal reflux disease (LPRD) patients from the normal population by pharyngeal pH (Dx-pH) monitoring, compared with the RYAN score. METHODS: One hundred and eight patients with suspected LPRD and complete follow-up results after more than 8 weeks of anti-reflux therapy were enrolled from the Department of Otolaryngology-Head and Neck Surgery, Gastroenterology and Respiratory Medicine of seven hospitals. Their Dx-pH monitoring data before treatment were reanalyzed to obtain the W score in addition to the RYAN score and then the diagnostic sensitivity and specificity were compared and evaluated with reference to the result of anti-reflux therapy. RESULTS: In eighty-seven (80.6%) cases, anti-reflux therapy was effective, and in 21 patients (19.4%), therapy was ineffective. Twenty-seven patients (25.0%) had a positive RYAN score. The W score was positive in 79 (73.1%) patients. There were 52 patients who had a negative RYAN score, but a positive W score. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of the RYAN score were 28.7%, 90.5%, 92.6%, and 23.5%, respectively (kappa = 0.092, P = 0.068), whereas those of the W score for LPRD was 83.9%, 71.4%, 92.4%, and 51.7%, respectively (kappa = 0.484, P < 0.001). CONCLUSIONS: W score is much more sensitive for the diagnosis of LPRD. Prospective studies with larger patient populations are necessary to validate and improve diagnostic efficacy. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800014931.

Ultrasound-guided fine-needle aspiration/biopsy-based pancreatic organoids establishment: an alternative model for basic and preclinical research.

Pancreatic ductal adenocarcinoma (PDAC), as one of the malignant cancers with the worst prognosis, is becoming the most urgent clinical problem. Due to the lack of early diagnosis and curable therapeutic methods, it is critical to exploit proper models that can capture the overall attributes of the primary tumor. Recently, organoid technology has emerged and flourished as a powerful tool to enable long-term culture of pancreatic tissues, including PDAC. As accumulating studies suggest, organoids can retain morphological, genetic, and behavioral traits, and have tremendous value in predicting the therapeutic response to conventional chemotherapy drugs or newfangled agents. Herein, this review comprehensively summarizes the tissue source including human fetal and adult pancreatic tissue to generate a pancreatic organoid as well as current organoids cultivate system. As PDAC organoids can be established from a small number of samples derived from endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB), we also review the literature to date on EUS-FNA/FNB-based organoid constitution and its implementation in inquiring tumor behavior and evaluating therapeutic responses. By enabling the alignment of basic and clinical research platforms, the application of organoids would open up new avenues for drug discovery and maximally benefit translational medicine in the near future.

Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper GI tract in cirrhotic patients with esophagogastric varices: 10-year experience from a large tertiary center in China.

BACKGROUND AND AIMS: Treatment strategies for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and esophagogastric varices (EGVs) are complicated and risky. The aim of this study was to assess the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of such patients and explore optimal treatment strategies. METHODS: We retrospectively enrolled 15 patients with cirrhosis and EGV who underwent ESD for early cancers or precancerous lesions of the upper GI tract from January 2012 to December 2021 at our center. Clinical features, endoscopic findings, treatment methods, adverse events, and follow-up data were analyzed. RESULTS: Of the 15 patients, 1 had a platelet count <30 × 1000/mm3. Five were untreated for EGV, 1 was treated after ESD, 6 were treated before ESD, 1 was treated before and during ESD, and 2 were treated during ESD. The R0 resection rate was 100%. Of the 16 mucosal lesions, 15 were endoscopic resection bleeding (ERB)-0 or ERB-c1, and 1 was ERB-c2. No patient experienced deterioration in liver function. The only adverse events were fever in 2 patients and postoperative bleeding in 2 patients. During a median follow-up of 27 months, 1 patient's esophageal high-grade dysplasia recurred at 19 months. No death resulted from the ESD procedure, liver function injury, or GI tumor itself. CONCLUSIONS: ESD is an effective and safe treatment for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and EGV. The incidence of severe adverse events is very low due to the development of individualized clinical treatment strategies.

Flexible intramedullary nails or Spica casting? A meta-analysis on the treatment of femur fractures in preschool children aged 2-5 years.

The objective of this study is to conduct a meta-analysis (1) to evaluate outcomes of flexible intramedullary nails (FIN) versus Spica casting for treating femur shaft fractures in children aged 2-5 years and (2) to investigate the associated complications. The PubMed , Cochrane Library , Embase and Web of Science databases were searched to identify available studies comparing the outcomes of FIN and Spica casting for the treatment of femoral shaft fracture in preschool children. Meta-analysis was conducted with adherence to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Eight observational studies involving 4995 patients were included. Two were judged to be of moderate quality, with the remainder being high quality. There were 1573 patients treated by FIN and 3422 by Spica casting. Compared to Spica casting, FIN allowed a quicker return to normal activities (40.49 ± 13.43 vs. 46.97 ± 14.32 days; P < 0.001), had a lower incidence of malunion (0.88 vs. 4.19%; P = 0.01) and unplanned interventions (2.87 vs. 7.53%; P < 0.001), but had slightly longer hospital stay (2.01 ± 1.01 vs. 1.10 ± 0.93 days; P = 0.01) and required a second surgery to remove the nails. Compared with Spica casting, FIN has the advantages of faster returning to normal activities and lower incidence of residual deformities and unplanned reoperation, but a slightly longer time of hospitalization and needs a second surgery to remove the hardware. Existing studies on duration of care and financial burden are insufficient, so further studies are warranted on multicenter and high-level evidence studies. Level of evidence: III.

Application of Multiphoton Microscopic Imaging in Study of Gastric Cancer.

Multiphoton microscopy (MPM) imaging relies on the nonlinear interaction between ultrashort optical pulses and the samples to achieve image contrast. Featuring larger penetration depth, less phototoxicity, 3-dimensional sectioning capability, no need for labeling, MPM become a powerful medical imaging technique that can identify structural characteristics of tissues at the cellular and subcellular levels. In this review paper, we introduce the working principle of MPM imaging, present the current results of MPM imaging applied to the study of gastric tumors, and discuss the future prospects of this interdisciplinary research field.

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.

Clinical efficacy of endoscopic antireflux mucosectomy vs. Stretta radiofrequency in the treatment of gastroesophageal reflux disease: a retrospective, single-center cohort study.

Background: Currently, antireflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) are the most commonly used minimally invasive antireflux therapies. To date, there have not been any reports comparing ARMS and SRF. Our aim was to compare the clinical efficacies of these two therapeutic methods. Methods: We analyzed data from gastroesophageal reflux disease (GERD) patients, including 39 who received ARMS treatment and 30 who received SRF treatment between January 2020 and May 2021. Symptom control, gastroesophageal reflux disease questionnaire (GERDQ) score, gastroesophageal reflux disease health-related quality of life (GERD-HRQL) score, proton pump inhibitor (PPI) withdrawal, and PPI reduction were analyzed and compared. Results: After 6 months of follow-up, the results showed that both therapies were effective in improving symptoms and quality of life. No difference was found between the ARMS group and SRF group in GERDQ score, GERD-HRQL score, PPI withdrawal rate, or PPI reduction rate (P>0.05). There was no significant difference in the PPI withdrawal rate between the two therapies among patients with gastroesophageal flap valve (GEFV) grade II and grade III (P>0.05), but the PPI withdrawal rate in the ARMS group was significantly higher than that in the SRF group among patients with GEFV grade IV (P<0.05). Conclusions: The clinical efficacies of ARMS and SRF 6 months postoperation were equivalent. The results showed that both ARMS and SRF treatment were acceptable for patients with GEFV grades II and III, while ARMS should be selected for patients with GEFV grade IV.

Identification of KANSL1 as a novel pathogenic gene for developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a common anomaly leading to adult osteoarthritis. Environmental and genetic factors contribute to DDH, but its exact genetic mechanism is unclear. In this study, we used whole exome sequencing to identify the causative gene of a DDH pedigree. A rare missense variant in KANSL1 (c.C767T; p.S256F) was identified as the pathogenic cause of DDH. Subsequent mutation screening showed another missense variant in 1 of 200 sporadic patients. Kansl1-mutated mice showed reduced chondrocytes in the acetabulum and a decrease in the cartilage matrix, which may be DDH phenotype-related abnormalities. Furthermore, functional studies showed that cell proliferation was delayed and Mmp13 expression was abnormally upregulated in chondrocytes differentiated from Kansl1 mutant mouse embryonic stem cells. In conclusion, our findings suggest that KANSL1 is a novel pathogenic gene for DDH. The identification of KANSL1 variants has great diagnostic value for identifying individuals with DDH. KEY MESSAGES: Developmental dysplasia of the hip (DDH) is a common anomaly causing adult osteoarthritis. Environmental and genetic factors contribute to DDH, but its exact genetic mechanism is unclear. Using high-throughput whole exome sequencing, we found a novel variant in KANSL1 that was co-inherited by all severely affected individuals diagnosed with DDH from a three-generation family. Further analysis revealed that a Kansl1 variant in mice reduced the number of chondrocytes and decreased cartilage matrix, and mouse embryonic stem differentiation assay showed cartilage defects. These findings indicate a direct association between KANSL1 and hip development, expanding the pathogenic gene spectrum in DDH and providing insight into potential new targets for diagnosing and treating hip dysplasia.