Objective To examine the safety, efficacy and durability of totally endoscopic minimally invasive (TEMI) mitral valve repair in Barlow’s disease (BD). Methods A retrospective study was performed on patients who underwent mitral valve repair for BD from January 2010 to June 2021 in the Guangdong Provincial People’s Hospital. The patients were divided into a MS group and a TEMI group according to the surgery approaches. A comparison of the clinical data between the two groups was conducted. Results A total of 196 patients were enrolled, including 133 males and 63 females aged (43.8±14.9) years. There were 103 patients in the MS group and 93 patients in the TEMI group. No hospital death was observed. There was a higher percentage of artificial chordae implantation in the TEMI group compared to the MS group (P=0.020), but there was no statistical difference between the two groups in the other repair techniques (P>0.05). Although the total operation time between the two groups was not statistically different (P=0.265), the TEMI group had longer cardiopulmonary bypass time (P<0.001) and aortic clamp time (P<0.001), and shorter mechanical ventilation time (P<0.001) and postoperative hospitalization time (P<0.001). No statistical difference between the two groups in the adverse perioperative complications (P>0.05). The follow-up rate was 94.2% (180/191) with a mean time of 0.2-12.4 (4.0±2.4) years. Two patients in the MS group died with non-cardiac reasons during the follow-up period. The 3-year, 5-year and 10-year overall survival rates of all patients were 100.0%, 99.2%, 99.2%, respectively. Compared with the MS group, there was no statistical difference in the survival rate, recurrence rate of mitral regurgitation, reoperation rate of mitral valve or adverse cardiovascular and cerebrovascular events in the TEMI group (P＞0.05). Conclusion TEMI approach is a safe, feasible and effective approach for BD with a satisfying long-term efficacy.

Epidemiology research has found that ABO blood group and the gene coding ABO glycosyltransferases are associated with many human diseases. The activity of ABO glycosyltransferases varies with different blood types, mediating different glycosylation modifications. The variation in glycosylation level might be the risk factor of specific disease. Based on the literature retrieval and analysis, glycosylation levels regulated by ABO glycosyltransferases mainly affect the ABH blood group antigens and von Willebrand factor (vWF). By modulating key glycosylation components, ABO glycosyltransferases partly determine the activity or expression levels of the ABH antigens and vWF, thereby affecting the development and progression of diseases. Exploring the pathogenic mechanisms of ABO glycosyltransferases can improve the understanding of the molecular pathology of related diseases and provide reference for clinical research and application.

Objective:To summarize the clinical characteristics of children with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) caused by c.489G>A (p.Pro163=) compound heterozygous variants in the ECHS1 gene, and to explore genotype-phenotype correlations.Methods:A case series study was performed to analyze clinical, biochemical, metabolic, imaging, genetic, treatment and follow-up outcomes of 24 children with ECHS1 gene c.489G>A(p.Pro163=) variant, who were diagnosed in the Department of Neurology, Beijing Children′s Hospital from July 2010 to June 2024. Disease severity was assessed using the Newcastle Paediatric Mitochondrial Disease Scale, and Fisher exact test was applied to compare the improvement rate between valine-restricted and non-restricted groups.Results:These 24 children were all diagnosed after 2022, with a disease duration of 3.35 (1.25, 6.52) years at diagnosis. A total of 8 children initially had negative genetic results, and were finally confirmed by abnormal splicing of ECHS1 gene via skin fibroblast RNA sequencing, with the longest diagnostic time of 14 years. All 24 children presented with Leigh syndrome, including 11 boys and 13 girls, with an onset age of 1.46 (0.96, 2.79) years; 16 children (67%) were mild cases. Common initial symptoms included developmental delay (9 cases) and paroxysmal dystonia (9 cases), followed by developmental regression (3 cases), nystagmus (2 cases), and epilepsy (1 case). Main manifestations were dystonia (18 cases), developmental regression (14 cases), nystagmus (12 cases), developmental delay (11 cases), ataxia (10 cases), vision loss (9 cases), seizures (2 cases), and hearing impairment (1 case). Among 22 children who underwent blood and urine metabolic screening, 21 children (95%) had elevated urinary 2, 3-dihydroxy-2-methylbutyric acid and 19 children (86%) had elevated urinary S-(2-hydroxypropyl) cysteamine. All 24 children had symmetric abnormal signals in bilateral globus pallidus on cranial magnetic resonance imaging, 10 children had isolated globus pallidus involvement, and other common involved sites included caudate nucleus and brainstem (9 cases each), putamen (7 cases), and cerebral white matter (5 cases). At last follow-up, all 24 children survived, with a follow-up duration of 5.40 (2.75, 8.02) years and a maximum age of 17.8 years; 17 children (71%) had varying degrees of clinical improvement. There was no statistical difference in the improvement rate between children with or without valine-restricted diet (12/14 vs. 5/8, P=0.309). A total of 18 pathogenic variants in the ECHS1 gene were identified among 24 children, 13 of which were distributed in exons 7 and 8; those carrying c.308T>C, c.523G>A, c.796A>G, and c.832G>A variants were mostly severe cases. Conclusions:Children carrying ECHS1 gene c.489G>A(p.Pro163=) compound heterozygous variants face significant diagnostic delay. Clinical awareness of this synonymous variant needs further improvement for timely diagnosis. All these cases present as Leigh syndrome, mostly mild, with no clear genotype-phenotype correlation identified.

Objective:To summarize the long-term efficacy of nicotinamide in treating pediatric early-onset progressive encephalopathy with brain edema and (or) leukoencephalopathy-2 (PEBEL2) caused by NAXD gene variation .Methods:This was a case report conducted from February 2019 to January 2025. The long-term efficacy of nicotinamide was observed by following up a child with PEBEL2 who received the treatment in the Department of Neurology, Beijing Children′s Hospital Affiliated to Capital Medical University. The clinical data included changes in skin lesions, neurological symptoms. The modified Rankin scale (mRS) was used to evaluate the recovery of neurological function.Results:A boy was diagnosed with PEBEL2 caused by NAXD gene variation via genetic testing at Beijing Children′s Hospital Affiliated to Capital Medical University in February 2019, when he was 4 years and 6 months of age. Immediately after diagnosis, nicotinamide treatment was initiated at an initial dose of 100 mg/d, which was increased by 100 mg per week and gradually increased to 500 mg/d; meanwhile, other therapeutic drugs were gradually discontinued. After 1 year and 8 months of treatment, the child′s skin lesions had completely resolved; at the 2-year follow-up, dystonia in both upper limbs and swallowing dysfunction was alleviated significantly; by 2.5-year follow-up, his cognitive function also showed improvement. When the child was treated with 500 mg/d for 3 years, a rash appeared around the mouth. After the dose was reduced to 250 mg/d, the rash resolved, and the dose of 250 mg/d was maintained until the last follow-up. At the last follow-up in January 2025, the child was 10 years and 5 months of age. His mRS score decreased from 5 (before treatment) to 4. During the 6-year of continuous nicotinamide treatment, the child′s condition remained stable without progression. Drug-related skin rashes occurred, but no severe drug-related adverse reactions were observed.Conclusions:PEBEL2 is a treatable mitochondrial disease. Nicotinamide treatment can effectively improve skin lesions and neurological symptoms in PEBEL2 patients, and the long-term administration demonstrates a favorable safety profile.

Epidemiology research has found that ABO blood group and the gene coding ABO glycosyltransferases are associated with many human diseases. The activity of ABO glycosyltransferases varies with different blood types, mediating different glycosylation modifications. The variation in glycosylation level might be the risk factor of specific disease. Based on the literature retrieval and analysis, glycosylation levels regulated by ABO glycosyltransferases mainly affect the ABH blood group antigens and von Willebrand factor (vWF). By modulating key glycosylation components, ABO glycosyltransferases partly determine the activity or expression levels of the ABH antigens and vWF, thereby affecting the development and progression of diseases. Exploring the pathogenic mechanisms of ABO glycosyltransferases can improve the understanding of the molecular pathology of related diseases and provide reference for clinical research and application.

Objective:To summarize the clinical characteristics of children with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) caused by c.489G>A (p.Pro163=) compound heterozygous variants in the ECHS1 gene, and to explore genotype-phenotype correlations.Methods:A case series study was performed to analyze clinical, biochemical, metabolic, imaging, genetic, treatment and follow-up outcomes of 24 children with ECHS1 gene c.489G>A(p.Pro163=) variant, who were diagnosed in the Department of Neurology, Beijing Children′s Hospital from July 2010 to June 2024. Disease severity was assessed using the Newcastle Paediatric Mitochondrial Disease Scale, and Fisher exact test was applied to compare the improvement rate between valine-restricted and non-restricted groups.Results:These 24 children were all diagnosed after 2022, with a disease duration of 3.35 (1.25, 6.52) years at diagnosis. A total of 8 children initially had negative genetic results, and were finally confirmed by abnormal splicing of ECHS1 gene via skin fibroblast RNA sequencing, with the longest diagnostic time of 14 years. All 24 children presented with Leigh syndrome, including 11 boys and 13 girls, with an onset age of 1.46 (0.96, 2.79) years; 16 children (67%) were mild cases. Common initial symptoms included developmental delay (9 cases) and paroxysmal dystonia (9 cases), followed by developmental regression (3 cases), nystagmus (2 cases), and epilepsy (1 case). Main manifestations were dystonia (18 cases), developmental regression (14 cases), nystagmus (12 cases), developmental delay (11 cases), ataxia (10 cases), vision loss (9 cases), seizures (2 cases), and hearing impairment (1 case). Among 22 children who underwent blood and urine metabolic screening, 21 children (95%) had elevated urinary 2, 3-dihydroxy-2-methylbutyric acid and 19 children (86%) had elevated urinary S-(2-hydroxypropyl) cysteamine. All 24 children had symmetric abnormal signals in bilateral globus pallidus on cranial magnetic resonance imaging, 10 children had isolated globus pallidus involvement, and other common involved sites included caudate nucleus and brainstem (9 cases each), putamen (7 cases), and cerebral white matter (5 cases). At last follow-up, all 24 children survived, with a follow-up duration of 5.40 (2.75, 8.02) years and a maximum age of 17.8 years; 17 children (71%) had varying degrees of clinical improvement. There was no statistical difference in the improvement rate between children with or without valine-restricted diet (12/14 vs. 5/8, P=0.309). A total of 18 pathogenic variants in the ECHS1 gene were identified among 24 children, 13 of which were distributed in exons 7 and 8; those carrying c.308T>C, c.523G>A, c.796A>G, and c.832G>A variants were mostly severe cases. Conclusions:Children carrying ECHS1 gene c.489G>A(p.Pro163=) compound heterozygous variants face significant diagnostic delay. Clinical awareness of this synonymous variant needs further improvement for timely diagnosis. All these cases present as Leigh syndrome, mostly mild, with no clear genotype-phenotype correlation identified.

Objective:To summarize the long-term efficacy of nicotinamide in treating pediatric early-onset progressive encephalopathy with brain edema and (or) leukoencephalopathy-2 (PEBEL2) caused by NAXD gene variation .Methods:This was a case report conducted from February 2019 to January 2025. The long-term efficacy of nicotinamide was observed by following up a child with PEBEL2 who received the treatment in the Department of Neurology, Beijing Children′s Hospital Affiliated to Capital Medical University. The clinical data included changes in skin lesions, neurological symptoms. The modified Rankin scale (mRS) was used to evaluate the recovery of neurological function.Results:A boy was diagnosed with PEBEL2 caused by NAXD gene variation via genetic testing at Beijing Children′s Hospital Affiliated to Capital Medical University in February 2019, when he was 4 years and 6 months of age. Immediately after diagnosis, nicotinamide treatment was initiated at an initial dose of 100 mg/d, which was increased by 100 mg per week and gradually increased to 500 mg/d; meanwhile, other therapeutic drugs were gradually discontinued. After 1 year and 8 months of treatment, the child′s skin lesions had completely resolved; at the 2-year follow-up, dystonia in both upper limbs and swallowing dysfunction was alleviated significantly; by 2.5-year follow-up, his cognitive function also showed improvement. When the child was treated with 500 mg/d for 3 years, a rash appeared around the mouth. After the dose was reduced to 250 mg/d, the rash resolved, and the dose of 250 mg/d was maintained until the last follow-up. At the last follow-up in January 2025, the child was 10 years and 5 months of age. His mRS score decreased from 5 (before treatment) to 4. During the 6-year of continuous nicotinamide treatment, the child′s condition remained stable without progression. Drug-related skin rashes occurred, but no severe drug-related adverse reactions were observed.Conclusions:PEBEL2 is a treatable mitochondrial disease. Nicotinamide treatment can effectively improve skin lesions and neurological symptoms in PEBEL2 patients, and the long-term administration demonstrates a favorable safety profile.

Objective To develop a novel transcatheter tricuspid valve replacement device and test its performance. Methods The transcatheter tricuspid valve stent consisted of double-layer self-expanding nitinol stent, biotissue-derived bovine pericardial leaflets, and PTFE woven. The delivery system, mainly consisting of a handle control unit and a delivery sheath, was sent to the correct position via right atrium or jugular vein. The sheath had a visualization feature, and the handle control unit could realize the functions of stable release and partial recovery of the interventional valve. In addition, this study performed animal survival experiments on the basis of in vitro experiments. A large-white pig was used as the experimental animal. Cardiopulmonary bypass was established through median thoracotomy, then the right atrium was opened, and the interventional valve was released under direct vision without cardiac arrest. Approximately 1 month after interventional valve implantation, the maneuverability and stability of the interventional tricuspid device were evaluated by autopsy. Results Through the animal experiment, the interventional valve was successfully released, and the anchoring was satisfactory. Postoperative transthoracic echocardiography showed that the interventional valve opened and closed well, the flow rate of tricuspid valve was 0.6 m/s, and there was no obvious tricuspid regurgitation. One month after the operation, we dissected the large-white pig and found the interventional valve was not deformed or displaced, the leaflets were well aligned, and there was thrombus attachment in the groove between the inner and outer layers of the interventional valve. Conclusion Animal experiment shows that the novel device can stably and firmly attach to the tricuspid annulus, with good anchoring effect, and effectively reduce paravalvular leakage.

Objective:To summarize the clinical characteristics of children carrying the m.8344A>G variant of MT-TK gene.Methods:A case series study was conducted to retrospectively collect data of 22 children with mitochondrial disease caused by MT-TK gene m.8344A>G variation who were treated at the Department of Neurology of Beijing Children′s Hospital of Capital Medical University from January 2012 to January 2024. Their clinical data, laboratory tests, muscle pathology, genetic testing, and the follow-up results were analyzed. Pearson correlation analysis was used for correlation analysis.Results:Among the 22 children, there were 13 boys and 9 girls. The age of onset was 5.00 (2.75, 9.00) years. Fifteen children had myoclonic epilepsy with ragged-red fibers (MERRF), 3 had Leigh syndrome (LS), and 4 had LS-MERRF overlap syndrome (LS-MERRF). Myoclonus presented and worsened progressively in all 15 MERRF children, with 10 as the initial symptom and 5 developing progressively during the disease course. Myoclonus was predominantly focal, worsening with fine motor tasks or stress. Electroencephalogram monitoring in the 15 MERRF children revealed myoclonic seizures in 10 children, with 6 classified as myoclonic epilepsy, and 4 as subcortical myoclonus. Two children had generalized myoclonic seizures, and 1 each had absence seizures and generalized seizures. Twelve children had cerebellar ataxia, 10 children exhibited exercise intolerance, and 8 children had muscle weakness. Magnetic resonance imaging (MRI) revealed periventricular white matter involvement in 1 child and bilateral hippocampal involvement in 1 child, likely due to frequent seizures. All 3 children with LS exhibited developmental regressions, accompanied with 2 symptoms include cerebellar ataxia, muscle weakness, and dysphagia. The clinical manifestations of 4 LS-MERRF overlap children presented with combined features of MERRF and LS. Cranial MRI in the 7 LS and LS-MERRF children showed brainstem involvement (all affecting the midbrain) in 6 children and basal ganglia involvement in 4 children. Among the 22 children, 12 had m.8344A>G variant levels >90%, 3 had >80%-90%, 4 had >70%-80%, and 3 had >60%-70%. Higher variant level correlated with the LS phenotype and earlier onset age ( r=0.47, -0.50; P=0.018 and 0.029, respectively). Sanger sequencing in 19 mothers revealed m.8344A>G variations in 18, with 4 showing exercise intolerance. Follow-up of 13 children on antimyoclonic treatment showed>75% reduction in seizures with levetiracetam monotherapy in 2 children, with combination therapy required in others. Most achieved >50% seizures reduction within 2 years, but the effectiveness declined with disease progression. Conclusions:The m.8344A>G variant is rare, with MERRF being the most common phenotype, while LS and LS-MERRF are less common. Children with higher ratio of the m.8344A>G variant are more likely to present LS phenotype. Myoclonus, primarily focal, is a key feature, with levetiracetam as the first-line treatment and benzodiazepines recommended for refractory cases.

Aging, a process of functional decline with the increase of chronological age, is a major risk factor for chronic diseases. Aging shows significant individual differences, which is influenced by both genetic and environmental factors. Accurate measurement of physiological age helps identify individuals with accelerated aging and those at high risk for chronic diseases and mortality, which would promote individual health management and precision medicine for healthy aging. In this paper, we summarize the omics-based aging clocks and discuss their current and future applications.