Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

Objective:To analyze the current status of registrations in randomized controlled trials (RCTs) of endovascular therapy for ischemic stroke.Methods:The ClinicalTrials.gov database was searched for RCTs of endovascular therapy for ischemic stroke from January 1, 1994 to June 30, 2024. The registration time, sites, sample size, complete status and design types, contents, and outcome evaluation methods of the trails were analyzed.Results:(1) A total of 195 RCTs were included. Number of RCTs registrations during 1994-2004, 2005-2014 and 2015-2024 were 2, 21 and 172, respectively. RCTs registration sites mainly concentrated in China, the United States and France, with 90 (46.1%), 29 (14.9%) and 24 (12.3%) registrations, respectively. There were 43 RCTs with sample size≤100 (22.1%), 143 RCTs with sample size of 100-1000 (73.3%), and 9 RCTs with sample size ≥1000 (4.6%). Fifty-seven RCTs were completed (29.2%, the average time from registration to trial completion was 1044 days); 91 RCTs (46.7%) were in the recruitment or pre-recruitment states; 23 RCTs (11.8%) were suspended or terminated. (2) RCTs design types included parallel design ( n=189, 96.9%), factorial design ( n=2, 1.0%), group-sequential design ( n=2, 1.0%), cross-over design ( n=1, 0.5%), and single-arm design ( n=1, 0.5%). Forty-four open trials (22.6%) and 151 blinded trials (77.4%) were recorded; among the blind trials, 108 RCTs (71.5%) were single-blind design, 19 (12.6%) were double-blind design, and 24 RCTs (15.9%) were triple-blind design. (3) A total of 69 RCTs (35.4%) focused on drug use, including 23 trails related to arterial thrombolysis drugs (mainly alteplase and tenecteplase); 67 RCTs (34.4%) were about endovascular therapy and perioperative management, among which 27 trials compared the efficacy of endovascular therapy, intravenous thrombolysis or placebo; 49 RCTs (25.1%) were about equipment use during treatment. (4) Outcome evaluation method: modified Rankin scale was most frequently used (153 RCTs), followed by National Institutes of Health Stroke Scale (100 RCTs). Conclusions:In the past decade, the number of RCTs about endovascular treatment for ischemic stroke has increased rapidly, and most of them were multi-center and blinded RCTs investigating the selection of arterial thrombolytic drugs, optimization of thrombectomy devices, and perioperative management. China is particularly prominent in this area of research.

Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

Objective:To analyze the current status of registrations in randomized controlled trials (RCTs) of endovascular therapy for ischemic stroke.Methods:The ClinicalTrials.gov database was searched for RCTs of endovascular therapy for ischemic stroke from January 1, 1994 to June 30, 2024. The registration time, sites, sample size, complete status and design types, contents, and outcome evaluation methods of the trails were analyzed.Results:(1) A total of 195 RCTs were included. Number of RCTs registrations during 1994-2004, 2005-2014 and 2015-2024 were 2, 21 and 172, respectively. RCTs registration sites mainly concentrated in China, the United States and France, with 90 (46.1%), 29 (14.9%) and 24 (12.3%) registrations, respectively. There were 43 RCTs with sample size≤100 (22.1%), 143 RCTs with sample size of 100-1000 (73.3%), and 9 RCTs with sample size ≥1000 (4.6%). Fifty-seven RCTs were completed (29.2%, the average time from registration to trial completion was 1044 days); 91 RCTs (46.7%) were in the recruitment or pre-recruitment states; 23 RCTs (11.8%) were suspended or terminated. (2) RCTs design types included parallel design ( n=189, 96.9%), factorial design ( n=2, 1.0%), group-sequential design ( n=2, 1.0%), cross-over design ( n=1, 0.5%), and single-arm design ( n=1, 0.5%). Forty-four open trials (22.6%) and 151 blinded trials (77.4%) were recorded; among the blind trials, 108 RCTs (71.5%) were single-blind design, 19 (12.6%) were double-blind design, and 24 RCTs (15.9%) were triple-blind design. (3) A total of 69 RCTs (35.4%) focused on drug use, including 23 trails related to arterial thrombolysis drugs (mainly alteplase and tenecteplase); 67 RCTs (34.4%) were about endovascular therapy and perioperative management, among which 27 trials compared the efficacy of endovascular therapy, intravenous thrombolysis or placebo; 49 RCTs (25.1%) were about equipment use during treatment. (4) Outcome evaluation method: modified Rankin scale was most frequently used (153 RCTs), followed by National Institutes of Health Stroke Scale (100 RCTs). Conclusions:In the past decade, the number of RCTs about endovascular treatment for ischemic stroke has increased rapidly, and most of them were multi-center and blinded RCTs investigating the selection of arterial thrombolytic drugs, optimization of thrombectomy devices, and perioperative management. China is particularly prominent in this area of research.

Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Objective To compare the short-term efficacy and occurrence of complication of endoscopic laminar fenestration (Endo-LOVE) and percutaneous endoscopic transforaminal decompression (PETD) in patients with degenerative lumbar lateral recess stenosis (LSLRS). Methods A total of 160 patients with LSLRS were enrolled as study objects, and were randomly assigned to control group (treated with PETD) and observation group (treated with Endo-LOVE), with 80 patients in each group. Surgical indicators, occurrence of complications, and therapeutic effects were observed and compared between the two groups. Bone lateral recess angle, soft lateral recess angle, Oswestry Disability Index (ODI) score, pain score, and Japanese Orthopaedic Association (JOA) score were compared before and after surgery. Results The observation group had less intraoperative blood loss, and shorter operative and hospital stays than the control group (P < 0.05). There were no statistically significant differences in the incidence of complications such as lower limb numbness, fever, and postoperative low back pain between the two groups (P>0.05). There were no statistically significant differences in preoperative bone lateral recess angle or soft lateral recess angle between the two groups (P>0.05). At 72 hours postoperatively, both angles increased in both groups compared with preoperative values, and the observation group had larger angles than the control group (P < 0.05). There were no statistically significant differences in preoperative pain score, ODI score, or JOA score between the two groups (P>0.05). At 3 months postoperatively, JOA scores increased and pain scores as well as ODI scores decreased in both groups compared with preoperative values, with the observation group having higher JOA scores and lower pain scores as well as ODI scores than the control group (P < 0.05). The excellent and good rate was 96.25%(77/80) in the observation group, which was higher than 87.50%(70/80) in the control group (P < 0.05). Conclusion Compared with the PETD approach, the Endo-LOVE approach for the treatment of LSLRS offers shorter operative time, less intraoperative blood loss, and better short-term efficacy.

Objective:To explore the genetic basis for a child featuring tetrahydrobiopterin deficiency and global developmental delay.Methods:Clinical and laboratory examinations were carried out for the child. Genomic DNA of the patient was subjected to high-throughput sequencing to identify genetic variants associated with hyperphenylalaninemia. Candidate variants were verified by Sanger sequencing.Results:The result of blood tandem mass spectrometry showed that the Phenylalanine in the blood was 642.7 μmol/l, and the ratio of Phenylalanine/Tyrosine was 5.42. Analysis of urinary pterin: neopterin 0.09 mmol/mol Cr, biopterin 0.04 mmol/mol Cr, biopterin% 77%, which suggested tetrahydrobiopterin deficiency. The parents of the proband were first cousins. DNA sequencing revealed that the proband has harbored homozygous c. 353A>T variants in exon 2 of the GCH1 gene, for which his great grandmother, grandfather, mother, uncle, father and elder brother were heterozygous carriers with normal phenotype and no clinical symptoms associated with dopa responsive dystonia. Conclusion:The homozygous c. 353A>T variant of the GCH1 gene probably underlay the tetrahydrobiopterin deficiency in this pedigree of consanguineous marriage.

Objective:To analyze the variation and characteristics of gene mutation in patients with 6-pyruvoyltetrahydropterin synthase deficiency(PTPSD) in Henan province, and to provide the theoretical basis for early diagnosis, treatment, genetic consultation and prenatal diagnosis of PTPSD.Methods:One thousand nine hundred and six children with hyperphenylalaninemia (HPA) treated in Henan Neonatal Screening Center, the Third Affiliated Hospital of Zhengzhou University from January 1998 to December 2018 were included.Chemiluminescence was used for pheny-lalanine (Phe) detection in blood or dried blood spots.For patients with Phe concentration >120 μmol/L, urine pterin analysis was carried out, and the activity of dihydropteridine reductase (DHPR) was detected.Mutations of the PAH, GCH1, GFRP, PCBD1, PTPS and QDPR in 79 children with tetrahydrobiopterin deficiency(BH4D) were detected by using the high-throughput sequencing.All variations were verified by Sanger sequencing. Results:Among the 1 906 children, 79 cases were diagnosed as BH4D clinically, and they all were PTPSD.The incidence of PTPSD in HPA in Henan was 4.14%.One hundred and fifty-six out of 158 alleles in 79 children were detected, and the detection rate of gene mutation was 98.73%, 30 mutations were identified and most of the variants were located in exons 5(92/156 cases, 58.97%). Variants of c. 259C>T (61/156 cases, 39.10%), c.286G>A (17/156 cases, 10.90%), c.155A>G (13/156 cases, 8.33%) and c. 272A > G (10/156 cases, 6.41%) were more common.Six novel variations were detected, which included c. -77G>T, c.158A>G, c.262C>T, c.207G>A, c.316A>G and c. 332C>G; 38 genotypes had been identified, including 3 homozygous mutations and 33 compound heterozygous mutations.Conclusions:c. 259C>T is the hot-spots gene mutation in Chinese PTPSD patients in Henan province.The identification of 6 new mutations enriches the gene mutation profile.

Objective: To study the prevalence, clinical and genetic characteristics of primary carnitine deficiency (PCD). Methods: From January 2013 to December 2017, 720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry. Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed. Dietary guidance and L-carnitine supplementation were provided to the parents. Growth and intelligence development were surveyed during follow-up. Results: In total 21 neonates and 6 mothers were diagnosed with PCD, which yielded an incidence of 1 in 34 317. Eighteen SLC22A5 mutations were detected, which included 4 novel mutations, namely c. 1484T>C, c. 394-1G>T, c. 431T>C and c. 265-266insGGCTCGCCACC. Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations. Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations. Common mutations included c. 1400C>G (42.3%), c. 760C>T (11.5%) and c. 51C>G (7.7%). During the 8 ~ 42 month follow-up, neonates with PCD showed no clinical symptoms but normal growth. Blood level of free carnitine was raised in all mothers after the treatment. Conclusion The incidence of neonatal PCD in Henan is 1 in 34 317, with the most common mutation being c. 1400C>G. Above finding has enriched the spectrum of SLC22A5 gene mutations.