Objective:To investigate the clinical and genetic features of patients with spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) caused by HACE1 gene mutation. Methods:Clinical data, auxiliary examination and genetic test results of a child with SPPRS caused by HACE1 gene mutation who was admitted to Henan Children′s Hospital in April 2019 were collected. The clinical and genotypic characteristics of children with SPPRS were summarized by searching the relevant literature up to June 2024, retrieved from CNKI, Wanfang and PubMed databases with the terms of " HACE1" "SPPRS" "seizures" "spastic paraplegia". Results:The patient was a 11 months and 20 days old male, with a clinical phenotype including global developmental delay, leg spastic tremor, frequent epileptic seizures, obesity, and concurrent urethral malformation. Brain magnetic resonance imaging (MRI) showed enlarged bilateral ventricles, hypoplastic corpus callosum, delayed myelination. Genetic test results revealed compound heterozygous variants c.994C>T (p.R332 *) and c.1679-2A>G in the HACE1 gene (according to the transcript NM_020771), respectively inherited from his mother and father, with c.1679-2A>G being a newly reported variant. A total of 6 English literatures reported 21 SPPRS patients in 11 families, and HACE1 gene mutations were mainly characterized by nonsense mutations. The main clinical manifestations included global developmental delay (21 cases), movement disorders (21 cases), intellectual disabilities (18 cases), seizures (13 cases), obesity (13 cases), skeletal abnormalities (11 cases), microcephaly (9 cases), ocular abnormalities (9 cases), distinctive facial features (5 cases), sensorineural hearing loss (5 cases), and short stature (3 cases). MRI predominantly showed hypoplasia of the corpus callosum, ventricular dilation, paucity of white matter and cerebral atrophy. There were no clear genotype-phenotype correlations. A total of 13 HACE1 gene mutations were reported, including 9 nonsense mutations, 2 frameshift mutations, 1 in-frame mutation, and 1 missense mutation. Among the 11 families, only 2 families with 5 patients were caused by compound heterozygous mutations, c.1852_1853del (p.L832del) and c.454C>T (p.Q152 *), c.2242C>T (p.R748 *) and c.2019_2020insTTTAGGTATTTTTAGGTATT (p.P674fs). The other 16 patients in 9 families were caused by homozygous mutations of the remaining 9 mutations. Conclusions:SPPRS is rare and usually occurs in infancy. The main clinical manifestations include comprehensive developmental delay, movement disorders, epilepsy, etc. Currently, no clear genotype-phenotype correlation has been found. The c.1679-2A>G variant of the HACE1 gene is an unreported variant and enriches the mutation spectrum of the HACE1 gene.

This review systematically polled the latest advancements in biomechanics research in competitive swimming during the Paris Olympic period together.By analyzing the application of biomechanics in competitive swimming,it reveals the key factors in performance improvement and injury prevention,mainly encompassing technique analysis and optimization,research method and equipment,performance evaluation and enhancement,and injury prevention and rehabilitation.Research related to biomechanics in competitive swimming for the Paris Olympic period highlights the significant role of biomechanics in optimizing swimming techniques,assessing athletic performance,and preventing injuries.Particularly,the advancement of sophisticated data collection and analysis equipment,such as high-precision sensors,artificial intelligence,and deep learning technologies,has made the analysis of swimming techniques more comprehensive and precise.Future research should further integrate multi-dimensional data technologies,employing high-precision motion capture,fluid mechanics measurement,and intelligent analysis to delve deeper into the pathways for optimizing swimming techniques.

AIM:To explore the expression of calcium binding and coiled-coil domain 2(CALCOCO2)in ani-mal models of atrial fibrillation(AF)and its role and mechanism in reversing atrial remodeling in AF mice.METHODS:Twelve rats and 12 mice were randomly divided into the following 2 groups(n=6 each):saline control group(saline group)and angiotensin Ⅱ(Ang Ⅱ)-induced AF group(Ang Ⅱ group).Western blot and immunohistochemistry(IHC)were used to detect CALCOCO2 expression in rat and mouse atrial muscle tissues.Another 24 mice were randomly divided into 4 groups(n=6 each):saline-oeNC,Ang Ⅱ-oeNC,saline-oeCALCOCO2,and Ang Ⅱ-oeCALCOCO2.An adeno-asso-ciated virus was used to induce CALCOCO2 overexpression in mouse atrial myocardium.Subsequently,transthoracic echocardiography and intracardiac electrophysiological testing were used to compare mouse cardiac function among the 4 groups.Western blot and TUNEL staining were also used to evaluate the effect of CALCOCO2 on apoptosis of cardiomyo-cytes in AF models.Additionally,IHC was used to assess the effect of CALCOCO2 on the levels of oxidative stress-related proteins[NADPH oxidase 2(NOX2)and NOX4]and fibrosis-related proteins[collagen type Ⅰ(Col Ⅰ),connexin 40(Cx40)and α-smooth muscle actin(α-SMA)]in AF atrial myocardium.RESULTS:The CALCOCO2 protein level in the atrial myocardium of rats and mice was significantly decreased in Ang Ⅱ group compared with saline group,as detected by Western blot and IHC(0.19±0.01 vs 0.32±0.03 for rats,0.37±0.10 vs 1.00±0.10 for mice,P<0.01).Compared with Ang Ⅱ-oeNC group,the mice in Ang Ⅱ-oeCALCOCO2 group exhibited decreased left atrial inner diameter,shorter AF duration,and increased ejection fraction(P<0.05).Semi-quantitative analysis of TUNEL staining revealed a signifi-cantly decreased apoptosis rate of mouse atrial myocytes in Ang Ⅱ-oeCALCOCO2 group compared with Ang Ⅱ-oeNC group(0.30±0.06 vs 0.61±0.03,P<0.01),which was consistent with the Western blot trend of apoptosis-related proteins such as BAX(1.94±0.34 vs 3.14±0.34,P<0.05)and cleaved caspase-3(2.19±0.41 vs 3.52±0.55,P<0.05).The semi-quantitative results of IHC and immunofluorescence revealed significantly increased levels of oxidative stress-related pro-teins(NOX2 and NOX4)and fibrosis-related proteins(Col Ⅰ and α-SMA),as well as decreased Cx40 levels,in Ang Ⅱ-oeNC group compared with saline-oeNC group.However,the expression levels of these proteins were significantly re-versed after CALCOCO2 overexpression(all P<0.05).CONCLUSION:Overexpression of CALCOCO2 reverses AF-in-duced electrical and structural remodeling by inhibiting the oxidative stress,apoptosis and fibrosis in mouse atrial tissues.

Objective:To investigate the correlation between characteristics of ultrasound image and expression levels of key genes in breast cancer.Methods:By searching the Medicine Pubmed database of the National Library,all the literatures related to relative genes of breast cancer were gathered.Search Tool for Retrieval of Interacting Genes/Proteins and Cytoscape software were used to construct protein-protein interaction(PPI)network for relative genes,and screen out key genes.The expression verification and prognostic analysis of candidate key genes were performed by Gene Expression Profiling Interactive Analysis and Kaplan Meier Plotter database bases on the values of gene expression levels.Retrospective analysis of 36 patients with breast cancer,who were confirmed by surgery and pathology in the First Hospital of Shanxi Medical University from September 2022 to September 2023,was performed.The expression of key genes of breast cancer was detected by the transcriptome sequence technique.The ultrasonographic features of patients with breast cancer were collected,and the correlation between it and key genes were further analyzed.Results:A total of 10 candidate key genes were identified,which included hyaluronic acid mediated motor receptors(HMMR),BUB1 mitotic checkpoint serine/threonine kinase(BUB1B),assembly factors of spindle microtubules(ASPM),cyclin dependent kinase(CDK1),serine/threonine protein kinase(BUB1),members of the driving protein family 2C(KIF2C),microtubule nucleation factor TPX2(TPX2),maternal embryonic leucine zipper kinase(MELK),centromere protein F(CENPF)and topoisomerase 2A(TOP2A).The above 10 candidate key genes were highly expressed in breast cancer samples and they had bad prognosis.The level of key gene TPX2 in patients whose maximum diameter of breast cancer>2cm was higher than that in patients whose the maximum diameter of breast cancer≤2cm,and the level of key gene MELK of patients with micro-calcification of breast cancer was significantly higher than that of patients without micro-calcification of breast cancer,and the differences of them were statistically significant(Z=-2.483,-2.888,P<0.05),respectively.The maximum elastic value(Emax)of shear wave elastography parameters was positively correlated with the expression levels of BUB1,KIF2C,TPX2,CENPF and TOP2A of key genes(r=0.411,0.399,0.447,0.446,0.337,P<0.05),respectively.Conclusion:Ultrasound characteristics of breast cancer can be used to predict the expression level of key genes,which can provide more bases for the choices of early diagnosis,treatment plan and prognostic assessment of breast cancer.

Objective:To explore the clinical phenotypic features and genetic variation characteristics of children with epilepsy-aphasia spectrum due to GRIN2A gene variants confirmed by second-generation sequencing. Methods:The clinical data of 5 children with epilepsy-aphasia spectrum with epileptic onset diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University, from February 2019 to November 2022 were retrospectively analyzed. Whole-exome genome sequencing of the probands using a second-generation sequencing method confirmed that all 5 cases were children with the GRIN2A gene variant. The characteristics of the GRIN2A gene variants were analyzed. Results:Among the 5 children diagnosed with epileptic aphasia spectrum due to GRIN2A gene variants, the male-to-female ratio was 4∶1, and the age range of onset was 1.5-4.4 years. The clinical phenotype included seizures in all cases, language and intellectual developmental deficits in 4 cases, and attention deficit hyperactivity disorder in 3 cases. The seizures were manifested as focal seizures or secondary generalized seizures, and were effectively controlled with antiepileptic drugs. Among the 5 children, gene variant of case 1 was originated from a paternal heterozygous variant, and cases 2-5 had de novo variants, which were c.2107C>T (p.Gln703 *) nonsense variant, c.2284G>A (p.Gly762Arg) missense variant, c.2197del (p.Ala733Glnfs *3) shifted coding variant, c.2511G>A (p.Trp837 *) nonsense variant, and c.1651+1G>C shear site variant, respectively. None of the 5 loci were reported in the literature. Conclusions:Epilepsy-aphasia spectrum is an epilepsy syndrome with a complex onset, and may have different phenotypes at different genetic variant loci, with focal seizures or secondary generalized seizures, which can be effectively controlled with anti-seizure medication. The GRIN2A gene variant is the genetic etiology of the epileptic aphasia spectrum.

Objective To explore the clinical features,diagnosis and treatment of liposarcoma of spermatic cord.Methods The clinical data of 1 case with multiple recurrence of liposarcoma of spermatic cord were retrospectively analyzed,and the clinical diagnosis and treatment were discussed in combination with relevant literature.Results The patient underwent the first operation to examine the adipocytes in the right spermatic cord area.Postoperative examination revealed highly differentiated liposarcoma.Within 1 year of follow-up,radical resection of both testis and retroperitoneal tumor were performed respectively due to recurrence.Conclusion liposarcoma of spermatic cord is an extremely rare disease,and currently there is no standard treatment protocol.Radical surgical resection of localized lesions is the key,and surgical treatment is still the first choice for local recurrence.As it is unable to achieve R0 resection,the recurrence rate is very high.Since liposarcoma is not sensitive to radiotherapy and chemotherapy,more precise adjuvant therapy is highly expected.

Objective:To investigate the correlation between clinical phenotypes and genetic characteristics of children with ring chromosomes (RCs).Methods:Case series study.The clinical data of 11 434 children who received treatment and peripheral blood chromosome karyotype detection in Henan Children′s Hospital from October 2008 to October 2023 due to growth retardation, intellectual impairment or congenital malformation were analyzed retrospectively.A total of 25 children with RCs were selected.Their age at diagnosis, karyotype distribution, clinical manifestations, and genetic detection results were analyzed.Results:RCs were detected in 25 out of 11 434 children, with a detection rate of 0.21%.The genome-wide copy number variation (CNV) analysis was performed on 7 RCs cases, and it found that pathogenic variation existed in all of them.Among the 25 RC cases (11 males and 14 females of social gender), the age at diagnosis ranged from 2 months to 14 years; there were 20 autosomal rings and 5 sex chromosome rings; 13 cases had chimeric karyotypes, and 12 cases had non-chimeric karyotypes.Most of the 25 children showed clinical manifestations of mental or developmental retardation, and some also presented with specific clinical manifestations, such as short stature, congenital malformation, and epilepsy.Conclusions:The pathogenesis of RCs is complex.The clinical manifestations are determined by both RCs syndrome and specific phenotypes caused by the dose effect and exhibit high heterogeneity, so it is easy to miss or misdiagnose.The combined application of cellular and molecular genetic detection technology can facilitate early diagnosis and treatment of RCs, and the correlation analysis of phenotypes and genetic characteristics can provide guidance for genetic counseling.

Objective:To develop and validate an artificial intelligence (AI) diagnostic model for coronary artery disease based on facial photos.Methods:This study was a cross-sectional study. Patients who were scheduled to undergo coronary angiography (CAG) at Beijing Anzhen Hospital and Beijing Daxing Hospital from August 2022 to November 2023 were included consecutively. Before CAG, facial photos were collected (including four angles: frontal view, left and right 60° profile, and top of the head). Photo datasets were randomly divided into a training set, a validation set (70%), and a testing set (30%). The model was constructed using Masked Autoencoder (MAE) and Vision Transformer (ViT) architectures. Firstly, the model base was pre-training using 2 million facial photos obtained from the publicly available VGGFace dataset, and fine-tuned by the training and validation sets; the model was validated in the test set. In addition, the ResNet architecture was used to process the dataset, and its outputs were compared with those of the models based on MAE and ViT. In the test set, the area under the operating characteristic curve ( AUC) of the AI model was calculated using CAG results as the gold standard. Results:A total of 5 974 participants aged 61 (54, 67) years were included, including 4 179 males (70.0%), with a total of 84 964 facial photos. There were 79 140 facial photos in the training and validation sets, with 3 822 patients with coronary artery disease; there were 5 824 facial photos in the test set, with 239 patients with coronary artery disease. The AUC value of the MAE and ViT model initialized with pre-training model weights was 0.841 and 0.824, respectively. The AUC of the ResNet model initialized with random weights was 0.810, while the AUC of the ResNet model initialized with pre-training model weights was 0.816. Conclusion:The AI model based on facial photos showes good diagnostic performance for coronary artery disease and holds promise for further application in early diagnosis.

Objective:To investigate the impact of the deep-learning-based CT fractional flow reserve (CT-FFR) on clinical decision-making and long-term prognosis in patients with obstructive coronary heart disease.Methods:In this single-center retrospective cohort study, consecutive patients with obstructive coronary heart disease (with at least one stenosis≥50%) on their first coronary computed tomography angiography (CCTA) in Beijing Anzhen Hospital from February 2017 to July 2018 were included. Baseline clinical and CT characteristics were collected. Deep-learning-based CT-FFR and Leiden CCTA risk score were calculated. All patients enrolled were followed up for at least 5 years. The study endpoint was major adverse cardiovascular events (MACE), defined as the composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and unplanned revascularization. Receiver operating characteristic (ROC) curves were drawn to define the optimal cut-off point of the Leiden score in predicting the 5-year MACE, and survival analysis and Cox regression were performed to explore the related factors of MACE.Results:A total of 622 patients, aged 61 (54, 66) years, with 407 (65.4%) males were included. Diagnostic coronary angiography was performed in 78 patients after their baseline CCTA, with 34 (43.6%) patients had CT-FFR>0.80. During a follow-up time of 2 181 (2 093, 2 355) days, 155 patients (24.9%) suffered from MACE. ROC derived optimal cut-off point of Leiden score for predicting MACE was 15.48. Survival analysis found that male patients, Leiden risk score>15 and CT-FFR≤0.80 had worse prognosis. Multivariate Cox regression analysis identified CT-FFR≤0.80 as an robust and independent predictor of MACE ( HR=4.98, 95% CI 3.15-7.86, P<0.001). Conclusion:Deep-learning-based CT-FFR aids in clinical decision-making and the evaluation of long-term prognosis in patients with obstructive coronary heart disease.

Objective:To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ).Methods:Clinical data of three children diagnosed with late-onset MADD at the Children′s Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years.Results:The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c. 1211T>C (p.M404T) and a maternal c. 488-22T>G variant in child 1, a paternal c. 1717C>T (p.Q573X) and a maternal c. 250G>A (p.A84T) variant in child 2, and a paternal c. 1285+ 1G>A and maternal c. 629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B2, levocarnitine and coenzyme Q 10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up. Conclusion:The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.