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The Shanghai soft X-ray Free-Electron Laser facility (SXFEL), which is the first X-ray FEL facility in China, is being constructed in two phases: the test facility (SXFEL-TF) and the user facility (SXFEL-UF). The test facility was initiated in 2006 and funded in 2014. The commissioning of the test facility was finished in 2020. The user facility was funded in 2016 to upgrade the accelerator energy and build two undulator lines with five experimental end-stations. The output photon energy of the user facility will cover the whole water window range. This paper presents an overview of the SXFEL facility, including considerations of the upgrade, layout and design, construction status, commissioning progress and future plans. [ABSTRACT FROM AUTHOR]

Menkes disease (MD) is a fatal X-linked multisystem disease caused by mutations in ATP7A. In this study, clinical and genetic analysis was performed in 24 male MD patients. Development delay, seizures, kinky coarse hair, and dystonia were found in 24, 22, 24, and 24 patients, respectively. Serum ceruloplasmin/copper tested in 19 patients was low. Abnormal classic features of MD presented in the MRI/MRA of 19 patients. Seventeen mutations of ATP7A were identified in 22 patients. Twelve were novel mutations including three small deletion/insertion, one missense mutation, two nonsense mutations, three splicing-site mutations, and three gross deletions. Twenty-two patients were genetically diagnosed; neither point mutation nor deletion/duplication was found in two of them. c.2179G > A found in five patients might be a hot-spot mutation. Prenatal molecular diagnosis was performed for five unrelated fetuses (1 female and 4 male), which found four fetuses to be wild type and one male carried the same mutation as the proband. This study of the largest sample of Chinese MD patients examined to date discovered the unique phenotype and genotype spectrum in Chinese patients with 12 novel mutations of ATP7A, and that c.2179G > A might be a hot-spot mutation in MD patients. Five successful prenatal diagnosis contributed important information for MD families. [ABSTRACT FROM AUTHOR]

To delineate the phenotype and genotype in Chinese children with type I Alexander disease (AxD) and the parental origin of de novo glial fibrillary acidic protein (GFAP) mutations. Twenty-two children with clinically diagnosed type I AxD were followed up for 1.66-6.62 years. Allele-specific PCR was used for the analysis of parental origin of the allele harboring the de novo mutation. Phenotype of these patients were consistent with type I AxD described in other population, with developmental delay (motor delay in 81.82%, cognitive delay in 63.64%), macrocephaly (100%), seizures (95.45%), paroxysmal deterioration (27.27%) and typical brain magnetic resonance imaging (100%). Progression was slower than reported. At 8.55 years of age (5.29-13.25), all patients who underwent the second follow-up were alive. Eleven heterozygous missense mutations of GFAP were identified in 21 patients, with three novel mutations. Reported hot spot mutations, p.R79, p.R239 and p.R88, were also identified in Chinese patients. Mutations were de novo in all but one case. The mother of a proband was demonstrated to be a presymptomatic patient with type II AxD with a p.R79H mutation. Ninety percent of de novo mutations were on the paternal allele demonstrated by allele-specific PCR. This is the largest follow-up study on Chinese children with AxD. The phenotypes of these patients are consistent with reports in other populations. GFAP mutations were identified in 95.46% of Chinese children with clinically diagnosed type I AxD. Our data suggested a male germ-line transmission. [ABSTRACT FROM AUTHOR]

Aim: To investigate the maternal homocysteine (Hcy), folate, vitamin B12 and B6, and their relations to neural tube defects (NTDs). Methods: Thirty mothers of NTDs offspring and another 60 mothers of normal children were enrolled as the patient and control groups from Xinjiang, China, from January 2008 to May 2011. The plasma levels of Hcy, folate, vitamin B12 and B6 were measured and compared between the two groups. Results: The morbidity of NTDs was 2.44% in Xinjiang. The Hcy was significantly higher in patient group than in control group (15.1 ± 7.8 vs. 8.5 ± 4.0 μmol/L, p < 0.001). The folate in patient group (9.7 ± 8.1 μg/L) was lower than in control group (15.0 ± 8.1 μg/L, p < 0.001). The vitamin B12 was 181.3 ± 107.7 and 394.3 ± 386.3 ng/L in patient and control groups, respectively, with a significant difference (p < 0.001). The abnormal frequency of Hcy and vitamin B12 was statistically different in two groups. The difference of vitamin B6 between the patients and controls was marginal (48.7 ± 16.5 vs. 42.0 ± 10.5 mg/L, p = 0.051). Moreover, folate and vitamin B12 levels were negatively correlated with Hcy while vitamin B6 was positively correlated with Hcy. Positive correlation was observed between folate and vitamin B12 levels. Conclusion: Our data confirm that higher Hcy, lower folate and vitamin B12 are risk factors for NTDs. Besides folate, vitamin B12 should be supplied to decrease NTDs occurrence. Further study is required to investigate the levels and accurate role of vitamin B6. [ABSTRACT FROM AUTHOR]

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal, recessively inherited disease caused by mutations in the MLC1 gene. Most of the previously published studies have been carried out in ethnic populations other than the Chinese. In this study, the analysis of clinical features and MLC1 mutation screening were performed in 13 Chinese patients for the first time. A total of 10 MLC1 mutations were identified in these patients, including five novel missense mutations (c.65G>A, p.R22Q; c.95C>T, p.A32V; c.218G>A, p.G73E; c.823G>A, p.A275T; c.832T>C, p.Y278H), one novel splicing mutation (c.772-1G>C in IVS9-1), one novel small deletion (c.907_930del, p.V303_L310del), one known nonsense mutation (c.593delCTCA, p.Y198X) and two known missense mutations (c.206C>T, p.S69L; c.353C>T, p.T118M). Mutation c.772-1G>C in IVS9-1, accounting for 27.3% (3/11) of the total number of genetically confirmed patients found in this study, is thus a putative hot-spot mutation in the present study group. The existence of a unique MLC1 mutation spectrum in Chinese MLC patients was shown. A systemic study to assess the mutation spectra in different populations should be undertaken. [ABSTRACT FROM AUTHOR]

Research and design of a C-band (5712 MHz) high-gradient traveling-wave accelerating structure is being carried out at Shanghai Institute of Applied Physics, Chinese Academy of Sciences. The structure consists of 53 regular disk-loaded cells and two waveguide couplers, and its length is about 1 m. This paper presents a design method for the accelerating structure, an experimental model and the preliminary results of an RF cold test of the model structure. [ABSTRACT FROM AUTHOR]

Objective: To investigate the contribution of genetic polymorphisms of vitamin K epoxide reductase complex subunit 1 gene VKORC1-1639G>A, cytochrome P450 2C9 gene ( CYP2C9), EPHXI, and clinical factors to warfarin sensitivity in southwest Chinese Han patients with mechanical heart valve prostheses. Methods: A total of 127 patients with mechanical heart valve prostheses who have been followed up at our department during the past 23 years were enrolled in this study and compared to a control group that consisted of 133 randomly selected healthy blood donors. These Chinese patients met stable warfarin dosage requirements and had reached the target international normalized ratio (INR) of 1.5-2.0. PCR and direct sequencing were carried out to identify the polymorphisms of VKORC1-1639G>A (rs9923231), CYP2C9*3 (rs1057910), CYP2C9 IVS3-65G>C (rs9332127), and EPHX1691A>G (rs4653436). In addition, total and free (non-protein-bound) warfarin concentrations were analyzed. Results and conclusions: There were great interindividual differences in warfarin maintenance dosage (ranging from 0.6 to 8.4 mg/day) among the 127 patients with mechanical heart valve prostheses. VKORC1-1639G>A, CYP2C9, EPHX1691A>G polymorphism, body weight, and age were found to affect the dose demands. Multiple linear regression models incorporating genetic polymorphisms of VKORC1, CYP2C9, EPHX1691A>G, and the nongenetic factors of age and body weight were developed, and explained up to 76.8% of the total variation (adjusted R of 0.743) in warfarin maintenance doses in southwest Chinese patients with mechanical heart valve prostheses. [ABSTRACT FROM AUTHOR]

Vanishing white matter (VWM) disease, inherited in an autosomal recessive manner, is one of the most prevalent inherited leukoencephalopathies in childhood. It is a hereditary human disease resulting from the direct defects during protein synthesis, with the gene defects in EIF2B1–5 (identified in 2001–2002) encoding the five subunits of eukaryotic translation initiation factor (eIF2B α, β, γ, δ and ɛ), respectively. Most of the published studies were carried out in the white population. The analysis of clinical features and EIF2B mutation screening were performed in 11 Chinese patients for the first time. Mutations were identified exclusively in EIF2B5 and EIF2B3 in these patients, with six novel mutations, including five missense mutations (EIF2B5: c.185A>T, p.D62V; c.1004G>C, p.C335S; c.1126A>G, p.N376D; EIF2B3: c.140G>A, p.G47E; c.1037T>C, p.I346T) and one deletion leading to amino-acid deletion (EIF2B5: c.1827–1838del, p.S610–D613del). EIF2B3 mutation, accounting for 20% of the total number of mutations found in this study, is more prevalent than expected according to an earlier report (7%). A hot spot mutation in EIF2B3 was identified in this study. A unique EIF2B mutation spectrum in Chinese VWM patients was shown. A systemic study to assess mutation spectrum in different populations needs to be carried out.Journal of Human Genetics (2009) 54, 74–77; doi:10.1038/jhg.2008.10; published online 16 January 2009 [ABSTRACT FROM AUTHOR]

Introduction: Automated bone age assessment (BAA) is of growing interest because of its accuracy and time efficiency in daily practice. In this study, we validated the clinical applicability of a commercially available artificial intelligence (AI)-powered X-ray bone age analyzer equipped with a deep learning-based automated BAA system and compared its performance with that of the Tanner-Whitehouse 3 (TW-3) method., Methods: Radiographs prospectively collected from 30 centers across various regions in China, including 900 Chinese children and adolescents, were assessed independently by six doctors (three experts and three residents) and an AI analyzer for TW3 radius, ulna, and short bones (RUS) and TW3 carpal bone age. The experts' mean estimates were accepted as the gold standard. The performance of the AI analyzer was compared with that of each resident., Results: For the estimation of TW3-RUS, the AI analyzer had a mean absolute error (MAE) of 0.48 ± 0.42. The percentage of patients with an absolute error of < 1.0 years was 86.78%. The MAE was significantly lower than that of rater 1 (0.54 ± 0.49, P = 0.0068); however, it was not significant for rater 2 (0.48 ± 0.48) or rater 3 (0.49 ± 0.46). For TW3 carpal, the AI analyzer had an MAE of 0.48 ± 0.65. The percentage of patients with an absolute error of < 1.0 years was 88.78%. The MAE was significantly lower than that of rater 2 (0.58 ± 0.67, P = 0.0018) and numerically lower for rater 1 (0.54 ± 0.64) and rater 3 (0.50 ± 0.53). These results were consistent for the subgroups according to sex, and differences between the age groups were observed., Conclusion: In this comprehensive validation study conducted in China, an AI-powered X-ray bone age analyzer showed accuracies that matched or exceeded those of doctor raters. This method may improve the efficiency of clinical routines by reducing reading time without compromising accuracy., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Background: Elderly individuals diagnosed with high-grade gliomas frequently experience unfavorable outcomes. We aimed to design two web-based instruments for prognosis to predict overall survival (OS) and cancer-specific survival (CSS), assisting clinical decision-making., Methods: We scrutinized data from the SEER database on 5,245 elderly patients diagnosed with high-grade glioma between 2000-2020, segmenting them into training (3,672) and validation (1,573) subsets. An additional external validation cohort was obtained from our institution. Prognostic determinants were pinpointed using Cox regression analyses, which facilitated the construction of the nomogram. The nomogram's predictive precision for OS and CSS was gauged using calibration and ROC curves, the C-index, and decision curve analysis (DCA). Based on risk scores, patients were stratified into high or low-risk categories, and survival disparities were explored., Results: Using multivariate Cox regression, we identified several prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in elderly patients with high-grade gliomas, including age, tumor location, size, surgical technique, and therapies. Two digital nomograms were formulated anchored on these determinants. For OS, the C-index values in the training, internal, and external validation cohorts were 0.734, 0.729, and 0.701, respectively. We also derived AUC values for 3-, 6-, and 12-month periods. For CSS, the C-index values for the training and validation groups were 0.733 and 0.727, with analogous AUC metrics. The efficacy and clinical relevance of the nomograms were corroborated via ROC curves, calibration plots, and DCA for both cohorts., Conclusion: Our investigation pinpointed pivotal risk factors in elderly glioma patients, leading to the development of an instrumental prognostic nomogram for OS and CSS. This instrument offers invaluable insights to optimize treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Jiang, Ren, Gu, Yao, Wang, Zou, Gan, Gu, Xu, Wang, Liu, Wang and Wei.)

Background: The natural history and genotype-phenotype correlation of Pelizaeus-Merzbacher disease (PMD) of Chinese patients has been rarely reported., Method: Patients who met the criteria for PMD were enrolled in our study. Genomic analysis was conducted by multiplex ligation probe amplification (MLPA) and Sanger or whole-exome sequencing (WES). Natural history differences and genotype-phenotype correlations were analyzed., Result: A total of 111 patients were enrolled in our follow-up study. The median follow-up interval was 53 m (1185). Among PMD patients, developmental delay was the most common sign, and nystagmus and hypotonia were the most common initial symptoms observed. A total of 78.4% of the patients were able to control their head, and 72.1% could speak words. However, few of the patients could stand (9.0%) or walk (4.5%) by themselves. Nystagmus improved in more than half of the patients, and hypotonia sometimes deteriorated to movement disorders. More PLP1 point mutations patients were categorized into severe group, while more patients with PLP1 duplications were categorized into mild group (p < 0.001). Compared to patients in mild groups, those in the severe group had earlier disease onset and had acquired fewer skills at a later age., Conclusion: PMD patients have early disease onset with nystagmus and hypotonia followed by decreased nystagmus and movement disorders, such as spasticit. Patients with PLP1 duplication were more likely to be categorized into the mild group, whereas patients with point mutations were more likely to be categorized into the severe group., (© 2022. The Author(s).)

Background: Intellectual disability/developmental delay is a complex condition with extraordinary heterogeneity. A large proportion of patients lacks a specific diagnosis. Next generation sequencing, enabling identification of genetic variations in multiple genes, has become an efficient strategy for genetic analysis in intellectual disability/developmental delay., Methods: Clinical data of 112 Chinese families with unexplained intellectual disability/developmental delay was collected. Targeted next generation sequencing of 454 genes related to intellectual disability/developmental delay was performed for all 112 index patients. Patients with promising variants and their other family members underwent Sanger sequencing to validate the authenticity and segregation of the variants., Results: Fourteen promising variants in genes EFNB1, MECP2, ATRX, NAA10, ANKRD11, DHCR7, LAMA1, NFIX, UBE3A, ARID1B and PTPRD were identified in 11 of 112 patients (11/112, 9.82%). Of 14 variants, eight arose de novo, and 13 are novel. Nine patients (9/112, 8.03%) got definite molecular diagnoses. It is the first time to report variants in EFNB1, NAA10, DHCR7, LAMA1 and NFIX in Chinese intellectual disability/developmental delay patients and first report about variants in NAA10 and LAMA1 in affected individuals of Asian ancestry., Conclusions: Targeted next generation sequencing of 454 genes is an effective test strategy for patients with unexplained intellectual disability/developmental delay. Genetic heterogenicity is significant in this Chinese cohort and de novo variants play an important role in the diagnosis. Findings of this study further delineate the corresponding phenotypes, expand the mutation spectrum and support the involvement of PTPRD in the disease.

Background: Brown-Vialetto-Van Laere Syndrome (BVVLS), a rare neurological disorder characterized by motor, sensory, and cranial neuronopathies, is mainly associated with defective riboflavin transporters encoded by SLC52A2 and SLC52A3 genes. Clinical outcomes have been shown to be improved significantly by high-dose riboflavin supplementation. The aim of this study was to identify genetic causes and further evaluate the clinical course and response to riboflavin in a Chinese pedigree with BVVLS., Case Presentation: We report the novel compound heterozygous variants c.1328G>A p.(Cys443Tyr) and c.1022&#95;1023insC p. (Leu341Profs*103) of SLC52A2 gene in a female proband who presented in our out-patient clinic at the age of one-year-old with progressive mental and motor regression, breath holding, and brain stem dysfunction including facial weakness, hearing loss, dysphagia. Following high-dose riboflavin supplementation, the respiratory insufficiency and mental, motor, and bulbar function improved. However, sensorineural hearing loss was not improved. The missense variant site was highly conserved. Both variants were not found in the population database gnomAD. The two variants were inherited from her mother and father, respectively. Both variants were predicted to be deleterious by Polyphen2, Mutation taster, and SIFT and were classified as likely pathogenic according to the ACMG guideline., Conclusions: Two novel pathogenic variations of SLC52A2 gene were firstly found from a Chinese pedigree with BVVLS. Clinical outcomes could be improved by early diagnosis and riboflavin supplementation.

Background: Fragile X syndrome is the most common genetic disorder of intellectual developmental disorder/mental retardation (IDD/MR). The prevalence of FXS in a Chinese IDD children seeking diagnosis/treatment in mainland China is unknown., Methods: Patients with unknown moderate to severe IDD were recruited from two children's hospitals. Informed consent was obtained from the children's parents. The size of the CGG repeat was identified using a commercial TP-PCR assay. The influence of AGG interruptions on the CGG expansion during maternal transmission was analyzed in 24 mother-son pairs (10 pairs with 1 AGG and 14 pairs with 2 AGGs)., Results: 553 unrelated patients between six months and eighteen years of age were recruited. Specimens from 540 patients (male:female = 5.2:1) produced high-quality TP-PCR data, resulting in the determination of the FMR1 CGG repeat number for each. The most common repeat numbers were 29 and 30, and the most frequent interruption pattern was 2 or 3 AGGs. Five full mutations were identified (1 familial and 4 sporadic IDD patients), and size mosaicism was apparent in 4 of these FXS patients (4/5 = 80%). The overall yield of FXS in the IDD cohort was 0.93% (5/540). Neither the mean size of CGG expansion (0.20 vs. 0.79, p > 0.05) nor the frequency of CGG expansion (2/10 vs. 9/14, p > 0.05) was significantly different between the 1 and 2 AGG groups following maternal transmission., Conclusions: The FMR1 TP-PCR assay generates reliable and sensitive results across a large number of patient specimens, and is suitable for clinical genetic diagnosis. Using this assay, the prevalence of FXS was 0.93% in Chinese children with unknown IDD.

Aim: To investigate the maternal homocysteine (Hcy), folate, vitamin B(12) and B(6) , and their relations to neural tube defects (NTDs)., Methods: Thirty mothers of NTDs offspring and another 60 mothers of normal children were enrolled as the patient and control groups from Xinjiang, China, from January 2008 to May 2011. The plasma levels of Hcy, folate, vitamin B(12) and B(6) were measured and compared between the two groups., Results: The morbidity of NTDs was 2.44% in Xinjiang. The Hcy was significantly higher in patient group than in control group (15.1 ± 7.8 vs. 8.5 ± 4.0 μmol/L, p < 0.001). The folate in patient group (9.7 ± 8.1 μg/L) was lower than in control group (15.0 ± 8.1 μg/L, p < 0.001). The vitamin B(12) was 181.3 ± 107.7 and 394.3 ± 386.3 ng/L in patient and control groups, respectively, with a significant difference (p < 0.001). The abnormal frequency of Hcy and vitamin B(12) was statistically different in two groups. The difference of vitamin B(6) between the patients and controls was marginal (48.7 ± 16.5 vs. 42.0 ± 10.5 mg/L, p = 0.051). Moreover, folate and vitamin B(12) levels were negatively correlated with Hcy while vitamin B(6) was positively correlated with Hcy. Positive correlation was observed between folate and vitamin B(12) levels., Conclusion: Our data confirm that higher Hcy, lower folate and vitamin B(12) are risk factors for NTDs. Besides folate, vitamin B(12) should be supplied to decrease NTDs occurrence. Further study is required to investigate the levels and accurate role of vitamin B(6)., (© 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.)

Objective: To delineate the phenotype and genotype characteristics in 12 Chinese children with Alexander disease (AD), which is helpful for the molecular diagnosis and genetic counseling in China., Methods: Clinical diagnosis of AD was based on MRI criteria proposed by van der Knaarp in 2001. Included AD patients were followed up for 0.50 - 3.67 years. Mutations in GFAP were detected by DNA sequencing., Results: The 12 cases of AD were clinically diagnosed. Age of first visit was 4.87 years (0.75 - 12.00 years), with 3 types of chief complaints: developmental delay in 3, recurrent seizures in 7, unable to walk after falling in 2. Average head circumference was 52.34 cm (44 - 58 cm), which larger than age-matched average by 6.45% (1.80% - 13.95%). On the first visit, scaling according to Gross motor functional classification system (GMFCS) was performed, with GMFCSI in 8, II in 3, V in 1. Mild to severe cognitive dysfunction were found in 8, and seizures in 11 cases. The 12 patients were followed up for 0.50 - 3.67 years, their motor and cognitive function remained stable. Episodic aggravations provoked by fever or falling were observed in 5 cases (41.67%). Heterozygous missense mutations of GFAP were detected in 12 patients. All mutations were de novo; 3 out of 10 mutations identified were novel. R79 and R239 were hot mutations, which was consistent with previous reports. Mutations were located in exon 1 in 8 cases., Conclusions: The phenotype in these patients is characterized by slower progression compared with reports from other population and high incidence of seizures. And episodic aggravations provoked by fever or falling were more common. The genotype characteristics are consistent with previous reports. The results of this research expanded the number of patients with Alexander disease found to have GFAP coding mutations in China.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC, MIM# 604004) is an autosomal recessive inherited disease mostly resulting from MLC1 mutations. In this study, we finished the functional analysis of MLC1 mutations identified recently in Chinese patients, including five newly described missense mutations (R22Q, A32V, G73E, A275T, Y278H), one known nonsense mutation (Y198X), and two known missense mutations (S69L, T118M). We found MLC1(wt) was localized to the cell periphery, whereas mutant R22Q, A32V, G73E, S69L and T118M were trapped in the lumen of endoplasmic reticulum (ER) when we transfected the wild-type and mutant MLC1 in U373MG cells. Compared to wild type, the mutant G73E, T118M, Y198X and A275T transcript decreased and all mutants except R22Q had lower protein expression in transfected U373MG cells. Therefore, we propose that all these eight MLC1 mutations had functional effect either on their protein/mRNA expression, or on their intracellular protein localization, or both.

An actinomycete, designated strain E71(T), was isolated from the stem of Sambucus adnata Wall, a Chinese medicinal plant, and subjected to a polyphasic taxonomic study. Phylogenetic analyses based on the 16S rRNA gene sequence showed that the organism was a member of the genus Glycomyces, and formed a distinct phyletic line distantly related to recognized species of the genus Glycomyces. Morphological and chemotaxonomic data supported the affiliation of strain E71(T) to the genus Glycomyces. A number of physiological properties and a unique menaquinone profile allowed differentiation of the strain from related Glycomyces species. It is therefore proposed that strain E71(T) represents a novel species of the genus Glycomyces, for which the name Glycomyces sambucus sp. nov. is proposed. The type strain is E71(T) (=CGMCC 4.3147(T)=DSM 45047(T)).

The taxonomic position of strain SD29(T), isolated from soil, was clarified using a polyphasic taxonomic approach. The organism produced an elementary branching mycelium which fragmented into rod/coccus-shaped elements and it possessed meso-diaminopimelic acid, arabinose, galactose as diagnostic diamino acid and sugars, MK-9(H(2)) as predominant menaquinone, phospholipids of type PII and mycolic acid. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain SD29(T) was most closely related to Gordonia hydrophobica DSM 44015(T) and Gordonia sihwensis DSM 44576(T), forming a distinct but loosely related branch in the phylogenetic tree. A number of physiological properties readily separated the isolate from its nearest neighbours. It is evident from genotypic and phenotypic data that strain SD29(T) represents a novel species of the genus Gordonia, for which the name Gordonia shandongensis sp. nov. is proposed. The type strain is SD29(T) (=CGMCC 4.3492(T)=JCM 13907(T)).