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This article examines recent Sino-US film collaborations, focusing on Mulan (2020) against the backdrop of geopolitical shifts and the COVID-19 pandemic. Through in-depth interviews and a case study, it investigates the lukewarm reception of Mulan (2020) in China. The study explores how external pressures have disrupted the previously thriving partnership, leading to investment uncertainty, intensified censorship, and shifts in audience consumption towards online platforms, which have exacerbated piracy issues. It also addresses the political tensions surrounding Mulan (2020), including controversies related to Xinjiang and Hong Kong, which hindered its box-office success in Mainland China despite domestic support. A comparative analysis with Mulan (1998) assesses the evolution of feminist themes and filial piety in the 2020 adaptation. The findings indicate that while efforts were made to enhance feminist narratives and cultural motifs, the execution was superficial, treating complex cultural themes as mere embellishments rather than integral elements of the narrative. The film's portrayal of these themes within a predominantly Western framework highlights ongoing challenges in bridging cultural narratives in Sino-US film productions. The findings underscore the profound impact of geopolitics and reveal the contentious portrayal of feminism and cultural integration in Mulan (2020), emphasizing the challenges in Sino-US film collaborations. [ABSTRACT FROM AUTHOR]

Despite the prolific film production in the nascent People's Republic of China (PRC) during the 'Seventeen Years' from 1949 to 1966, Maoist cinema received limited critical analysis. While recent scholarly attention has shifted towards examining Chinese film production and exchange within the socialist bloc, a notable gap remains in the literature concerning Sino-Arab film collaboration during this period. This paper seeks to address this gap by utilizing textual analysis and archival studies to explore the practice of Sino-Arab film weeks through the lens of cultural diplomacy. Building upon the framework of the three schools of thought on cultural diplomacy, this study posits that Sino-Arab film collaboration from the 1950s to 1960s operated within the realm of people's diplomacy. This term denotes cultural diplomacy with distinctively Chinese attributes within the Cold War context. This paper also complements the third trend that focuses on the transcendental realm of the state by exploring the little-studied interactions between film screenings and reality in Sino-Arab film weeks. Under the common goal of anti-imperialism and nation-building, people's diplomacy deviates from the conventional paradigm of bipolar rivalry and embodies the spirit of internationalist solidarity among Third World countries. [ABSTRACT FROM AUTHOR]

In light of the shift from the first phase to the second phase of transnational cinema studies, this volume examines a set of practices of transnational cinema that have been taking place between China and its counterparts. In exploring transnational cinema activities in the form of film collaborations and co-productions, this volume puts the spotlight on critical trends in transnational cinemas that are not limited to Western spheres of influence. Focusing on practical applications of case studies between China, Arab countries, Denmark and the U.S. it contributes to the debates on the definition and practical applications for research on film collaboration and co-production and transnational cinema studies. [ABSTRACT FROM AUTHOR]

Background: cblC deficiency is the most common type of methylmalonic aciduria in China. Late-onset patients present with various non-specific symptoms and are usually misdiagnosed. The purpose of this study is to investigate the clinical features of patients with late-onset cblC deficiency and explore diagnosis and management strategies around puberty.Results: This study included 56 patients (35 males and 21 females) with late-onset cblC deficiency who were admitted to our clinic between 2002 and September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome, and associated genetic variants were examined. The onset age ranged from 10 to 20 years (median age, 12 years). Fifteen patients (26.8%) presented with symptoms after infection or sports training. Further, 46 patients (82.1%) had neuropsychiatric diseases; 11 patients (19.6%), cardiovascular diseases; and 6 patients (10.7%), pulmonary hypertension. Renal damage was observed in 6 cases (10.7%). Genetic analysis revealed 21 variants of the MMACHC gene in the 56 patients. The top five common variants detected in 112 alleles were c.482G > A (36.6%), c.609G > A (16.1%), c.658_660delAAG (9.8%), c.80A > G (8.0%), and c.567dupT (6.3%). Thirty-nine patients carried the c.482G > A variant. Among 13 patients who exhibited spastic paraplegia as the main manifestation, 11 patients carried c.482G > A variants. Six patients who presented with psychotic disorders and spastic paraplegia had compound heterozygotic c.482G > A and other variants. All the patients showed improvement after metabolic treatment with cobalamin, L-carnitine, and betaine, and 30 school-aged patients returned to school. Two female patients got married and had healthy babies.Conclusions: Patients with late-onset cblC deficiency present with a wide variety of neuropsychiatric symptoms and other presentations, including multiple organ damage. As a result, cb1C deficiency can easily be misdiagnosed as other conditions. Metabolic and genetic studies are important for accurate diagnosis, and metabolic treatment with cobalamin, L-carnitine, and betaine appears to be beneficial. [ABSTRACT FROM AUTHOR]

• Compound heterozygote is the most frequent type of HoFH in China. • The diagnosis and treatment of HoFH is delayed and uncontrolled. • HoFH patients often have structural cardiac abnormalities since early childhood. • True HoFH have worse survival rates compared to other genotype probands. There is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia. To define the characteristics of phenotypic and genetic HoFH probands from mainland China. We collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test. A total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH. This report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH. [ABSTRACT FROM AUTHOR]

Background: Methylmalonic aciduria (MMA), a rare inherited disorder, is the most common organic aciduria in China, and prenatal diagnosis has contributed to its prevention. However, the prenatal diagnosis of MMA using cultured amniocytes or chorionic villi to detect gene mutations is exclusively applicable to families with a definite genetic diagnosis. To evaluate the reliability of mass spectrometry assays for the prenatal diagnosis of MMA, we conducted a retrospective study of our 10 years' experience. Materials and methods: This retrospective compare study reviewed the medical records for maternal and fetuses data for 287 mothers with a family history of MMA from June 2010 to December 2020. Methylmalonate and propionylcarnitine in cell-free amniotic fluid were measured using a stable isotope dilution method (GC/MS) and MS/MS-based method (LC/MS/MS). Total homocysteine (tHcy) was measured by fluorescence polarization immunoassay. Depending on the presence of disease-causing gene mutations in probands, gene studies on amniocytes from 222 pregnant women were performed. Results: For 222 fetuses of the families with definite genetic diagnosis, gene analyses were performed using cultured amniocytes. 52 fetuses were affected by MMA, whereas 170 were "unaffected". For GC/MS and LC/MS/MS, the specificity was 96.5% and 95.9%, sensitivity was 71.2% and 84.6%, respectively. The positive and negative predictive values were 86.0% and 91.6% and 86.3% and 95.3%, respectively. Propionylcarnitine/butyrylcarnitine ratio showed the highest accuracy and could thus serve as a sensitive indicator to identify those at a risk for MMA. When GC/MS and LC/MS/MS were performed in parallel, the specificity was 92.5% and sensitivity was 95.6%. When evaluating tHcy, the positive and negative predictive values were 95.0% and 96.1%, respectively. In 65 fetuses without family genetic diagnosis, 11 were finally confirmed to have MMA and 54 were "unaffected" by amniotic fluid biochemical assays. The 54 children showed normal urine organic acids and healthy development after birth. Conclusions: Amniotic fluid biochemical assays using GC/MS and LC/MS/MS in parallel increased the accuracy of prenatal diagnosis of MMA. Propionylcarnitine is a more reliable marker than methylmalonic acid in amniotic fluid. Further, tHcy is recommended for the prenatal diagnosis of combined MMA and homocysteinemia. [ABSTRACT FROM AUTHOR]

Summary: This article explores the role of non-state actors from the film industry in promoting China's soft power. Much research on non-state actors has emphasised the Anglophone world, while little research has been undertaken in the context of non-democratic regimes such as China. Therefore, following scholarly reviews on soft power and the role of its key actors, this article analyses China's approach to soft power, based on semi-structured interviews conducted with film experts to explore the role of non-state actors in generating soft power. The study reveals that although China has consistently privileged state-owned actors over non-state actors, non-state actors have actually played an increasingly important role in disseminating soft power. The article argues that the more powerfully the Chinese authorities emphasise China's state actors, the less likely it is that China will win hearts and minds — because of China's domestic political ideology and censorship mechanism in the field. [ABSTRACT FROM AUTHOR]

The clinical, biochemical and mutation spectra of Chinese patients with Type III Bartter syndrome (type III BS), a rare autosomal recessive disorder, were investigated. A total of five unrelated Chinese patients aged 8 months to 24 years were diagnosed with type III BS via analysis of biochemical markers, including chloride, potassium and calcium, and genetic sequencing. The levels of insulin-like growth factor-1 (IGF-1) were evaluated via ELISA and a mutation study of cultured amniocytes was conducted for prenatal diagnosis. The child patients were admitted for polydipsia, polyuria, myasthenia and developmental delay, whereas the adult patients were hospitalized for limb numbness, polydipsia and polyuria. Nine variants in the chloride voltage-gated channel Kb (CLCNKB) gene were detected, including eight sequence variants and one whole CLCNKB gene deletion. One sequence variant (c.1967T>C) was novel, whereas the remaining variants (c.595G>T, c.908A>C, c.1004T>C, c.1312C>T, c.1334_1335delCT and c.1718C>A) and the whole gene deletion had been previously reported. The whole gene deletion was frequently observed in patients with early-onset type III BS in the present study. Two patients showed IGF-1 deficiency with normal growth hormone level. All patients were treated with potassium supplementation and indometacin. The mother of one patient underwent amniocentesis during her second pregnancy; the fetus was not affected by type III BS based on screening for sequence variants, and normal development and blood electrolyte analysis following birth confirmed the diagnosis. In conclusion, five cases of type III BS in patients from mainland China were reported. Large deletions were frequently detected, particularly in early-onset patients; isolated IGF-1 deficiency was found, one novel sequence variant was identified. Prenatal diagnosis was successfully established using genetic analysis of cultured amniocytes, and may facilitate the prevention of congenital defect of type III BS in the next pregnancy. [ABSTRACT FROM AUTHOR]

Background: Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder that affects glyoxylate metabolism. PH3 is caused by defects in 4-hydroxy-2-oxoglutarate aldolase, which is encoded by the HOGA1 gene. However, only 3 cases of PH3 have been described in Asians until today. This study aimed to determine the clinical and mutation spectra of patients from mainland China with PH3. Methods: We applied targeted next-generation sequencing to four non-consanguineous, unrelated Chinese families with PH3 to identify the genes hosting disease-causing mutations. This approach was confirmed by Sanger sequencing. Results: Five patients (2 boys and 3 girls) from four unrelated Chinese families were admitted because of kidney stones. Five HOGA1 gene sequence mutations were detected, including two novel mutations, c.811C>T (p.R271C) and c.812G>A (p.R271H). These compound heterozygous mutations were detected in a female PH3 patient (patient 4). Other patients included 2 boys who had heterozygous c.834_834+1GG>TT and c.834G>A (p.A278A) mutations (patients 1 and 2), a girl with homozygous c.834G>A (p.A278A) mutation (patient 3), and a girl with heterozygous c.834_834+1GG>TT and c.346C>T (p.Q116X) mutations (patient 5). The mutations in the c.834_834+1 region, including c.834G>A, c.834+1G>T, and c.834_834+1GG>TT, account for 5/8 of alleles in our study and 3/4 of alleles reported among Chinese patients. All patients in this study received hyperhydration and urine alkalinization treatment. Conclusion: Five PH3 cases were reported. Potential mutation hot spot region (c.834_834+1) in the Chinese population and two novel mutations were found. [ABSTRACT FROM AUTHOR]

To investigate the prevalence and the associated risk factors of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and sexually transmitted infections (STIs) among men who have sex with men (MSM) in Kunming, 300 MSM were recruited through community-based organizations between September 2014 and January 2015. The prevalence of HIV, HBsAg, syphilis, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) were 17.0%, 7.7%, 11.3%, 18.2% and 13.2%, respectively. In the three different anatomic sites (urethra, rectum and pharynx), the prevalence of rectal CT was the highest (15.5%), whereas NG was most commonly found in the pharynx (8.1%). Low education level, homosexuality, inconsistent condom use and drug use in the previous six months were significantly associated with HIV infection, whereas the former three factors were also associated with HBV infection.Older people (aged ≥ 40 years) and those who lacked knowledge of STIs, and younger people (aged <30 years) as well as inconsistent condom users were more at risk of syphilis and CT infections, respectively. NG infection was only associated with reported dating venues. Our study revealed a heavy disease burden and multiple risk factors of HIV/STIs among MSM in Kunming. It is necessary to promote regular screening and proactive treatment of HIV/STIs among MSM. [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]

This article examines how the Chinese ruling party understands the role of film and how film policy has been used to promote China's soft power. It first explores shifts in policy over a period of 60 years in order to identify the government's overall approach to the film industry. Then it investigates 'Zou Chu Qu', the so-called 'Going-Out Policy', specifically aimed at promoting soft power. This article argues that, although the role of the film industry has been adjusted in response to developments in Chinese society, the principal function of film as a tool of propaganda, along with the broader censorship system, has not fundamentally changed. Such policy arrangements have resulted in a tension between the 'attraction' of soft power and the state's attraction to censorship. Consequently, there currently seems little room for Chinese films to contribute to China's soft power in any meaningful way. [ABSTRACT FROM AUTHOR]

Muscle-eye-brain (MEB) disease is a congenital muscular dystrophy (CMD) phenotype characterized by hypotonia at birth, brain structural abnormalities and ocular malformations. To date, few MEB cases have been reported in China where clinical recognition and genetic confirmatory testing on a research basis are recent developments. Here, we report the clinical and molecular genetics of three MEB disease patients. The patients had different degrees of muscle, eye and brain symptoms, ranging from congenital hypotonia, early-onset severe myopia and mental retardation to mild weakness, independent walking and language problems. This confirmed the expanding phenotypic spectrum of MEB disease with varying degrees of hypotonia, myopia and cognitive impairment. Brain magnetic resonance imaging showed cerebellar cysts, hypoplasia and characteristic brainstem flattening and kinking. Four candidate genes ( POMGnT1, FKRP, FKTN and POMT2) were screened, and six POMGnT1 mutations (four novel) were identified, including five missense and one splice site mutation. Pathogenicity of the two novel variants in one patient was confirmed by POMGnT1 enzyme activity assay, protein expression and subcellular localization of mutant POMGnT1 in HeLa cells. Transfected cells harboring this patient's L440R mutant POMGnT1 showed POMGnT1 mislocalization to both the Golgi apparatus and endoplasmic reticulum. We have provided clinical, histological, enzymatic and genetic evidence of POMGnT1 involvement in three unrelated MEB disease patients in China. The identification of novel POMGnT1 mutations and an expanded phenotypic spectrum contributes to an improved understanding of POMGnT1 structure-function relationships, CMD pathophysiology and genotype-phenotype correlations, while underscoring the need to consider POMGnT1 in Chinese MEB disease patients. [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]

• Eight mutations of the ACADVL gene were identified from six Chinese VLCAD deficiency patients. • Three novel mutations [c.563G > A (p.G188D), c.1387G > A (p.G463R) and c.1582_1586del (p.L529Sfs*31)] were found. • The mutation p.R450H is firstly regarded as the hotspot mutation in the Chinese population. Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD deficiency), a rare autosomal recessive disorder, is characterized by hypoketotic hypoglycemia, cardiomyopathy, liver damage, and myopathy. VLCAD deficiency is caused by defects of ACADVL gene, which encodes VLCAD protein. The aim of this study was to determine the clinical, biochemical, prognosis and mutation spectrum of patients with VLCAD deficiency in mainland China. A total of Six families visited us, four patients (2 boys and 2 girls) were admitted in hospital due to liver dysfunction, hypoglycemia, and positive newborn screen result. The parents of the other two patients (2 girls) visited us for genetic consultation after their children's death. All the six patients had elevated level of serum tetradecenoylcarnitine (C14:1-carnitine), four of them showed decreased free carnitine (C0) level, and three had dicarboxylic aciduria. Eight types of mutations of the ACADVL gene were detected, three of them are novel, including c.563G > A (p.G188D) c.1387G > A (p.G463R) and c.1582_1586del (p.L529Sfs*31). The p.R450H mutation accounts for 9/52 alleles (5/40 in previous study of 20 unrelated patients, and 4/12 in this study) of genetically diagnosed Chinese VLCAD deficiency cases. The four alive patients (Patient 1–4) responded well to diet prevention and drug therapy with stable hepatic dysfunction condition. In conclusion, we describe three novel mutations of the ACADVL gene among six unrelated families with VLCAD deficiency. Moreover, we suggest that the p.R450H may be a potential hotspot mutation in the Chinese population. [ABSTRACT FROM AUTHOR]

Isovaleric acidemia (IVA), a rare autosomal recessive disorder in leucine metabolism caused by defected IVD gene, is characterized by episodes of acute metabolic crisis and psychomotor development retardation. This study aimed to determine the clinical, biochemical, and mutation spectrum of patients with IVA from mainland China. Eight patients (three boys and five girls) from eight unrelated families were collected, IVD gene mutations and phenotypes were examined. The patients were admitted because of vomiting, feeding difficulty, psychomotor retardation and "dirty sock" odor. Elevated blood isovaleryl (C5)-carnitine and urine isovalerylglycine were detected from all our patients. Fourteen mutations of the IVD gene were detected, eight of them are novel, c.145C>T (p.Q49Ter), c.359G>A (p.R120Q), c.424C>T (p.R142C), c.458T>C (p.L153P), c.466-1G>T, c.676_677insA (p.T226Nfs*13), c.1039G>A (p.A347T) and c.1076A>G (p.D359G). With this study, a total of 34 alleles were studied in the Chinese population. c.1208A>G (p.Y403C), the common mutation in Taiwan, accounts for 9/34 alleles (7 in previous reports and 2 in this study). We described eight novel mutations detected from eight unrelated Chinese patients and provided evidence to support that the p.Y403C is the hotspot mutation in this population. • Fifteen mutations of the IVD gene were identified from eight Chinese IVA patients. • Eight novel mutations were found. • The mutation p.Y403C is the hotspot mutation in the Han Chinese population. [ABSTRACT FROM AUTHOR]

The installed capacity of ultrafiltration (UF) membranes in drinking water treatment plants (DWTPs) has increased significantly, it is necessary to summarize the long-term characteristics of UF membranes in full-scale DWTPs in China. Firstly, the characteristics of UF membranes applied in large-scale DWTPs in China were systematically evaluated based on capacity, location, membrane materials and filtration mode. By 2020, the total capacity of large-scale DWTPs using UF membranes has reached ~10 million m3/d. Polyvinylidene fluoride was the dominant UF membrane material with a proportion of 73.7 %, followed by polyvinyl chloride. Secondly, the performance of UF membranes in various typical DWTPs during long-term operation was analyzed. UF membrane in five typical treatment processes displayed good contaminant removal performance, while the combination of UF membrane with coagulation, sedimentation and filter was widely used. The fouling evolution of UF membranes during long-term operation was systematically analyzed. Then, the effect of pretreatment methods and cleaning approaches on membrane in full-scale DWTPs were assessed. The use of hydraulic cleaning, maintenance cleaning and recovery cleaning could ensure the stable operation of UF membranes, while these cleaning methods may adversely influence membrane lifetime. This study could provide useful guidance for long-term operation of UF membrane in full-scale DWTPs. [Display omitted] • UF membrane in 106 full-scale DWTPs in China reached ~10 million m3/d by 2020. • DWTPs with UF displayed spatial distribution, with most in Eastern China. • Combination of UF with traditional drinking water treatment units employed widely. • PVDF occupied 73.7 % of membrane material and 60 % of UF operated at submerged mode. • Over half of the UF membranes in full-scale DWTPs operated for over 5 years. [ABSTRACT FROM AUTHOR]

Objective 5-Oxoprolinuria is a rare inherited metabolic disorder caused by a defective gamma-glutamyl cycle resulting from mutations in the genes encoding 5-oxoprolinase ( OPLAH ) and glutathione synthetase ( GSS ). No inherited 5-oxoprolinuria case has been reported in mainland China until now. In this study, clinical, biochemical, and genetic aspects of five Chinese 5-oxoprolinuria patients with OPLAH or GSS gene mutations were investigated. Methods Three boys and two girls from five unrelated Chinese families with symptomatic 5-oxoprolinuria were identified within the past 3 years in Peking University First Hospital. OPLAH and GSS genes were analyzed. Results Patients were hospitalized between the age of 13 days to 1 year and 3 months for hypersomnia, developmental retardation, feeding deficiency, vomiting, icterus and recurrent pneumonia. All patients had significantly elevated urine 5-oxoproline. Three novel mutations (c.1904G>A and c.2813_2815delGGG in Patient 1, c.2978G>T in Patient 2) on OPLAH , on GSS , one novel mutation (c.1252C>T in Patient 3) and a reported mutation (c.491G>A in Patients 3–5) were detected. Patient 4 has homozygous mutation c.491G>A, the others are heterozygous. After treatment by l -carnitine, vitamin E, B1, B2 and coenzyme Q 10 , three patients with GSS deficiency improved, but the two 5-oxoprolinase-deficient patients did not respond to treatment. Conclusions 5-Oxoprolinase deficiency and GSS deficiency share some clinical and biochemical features. Genetic analysis is important for the deferential diagnosis. In this study, five Chinese patients had severe central nervous system damage. Antioxidant treatments were proved effective for the three patients with GSS deficiency but not for the two patients with 5-oxoprolinase deficiency. [ABSTRACT FROM AUTHOR]

Abstract: To evaluate eight frequently encountered mitochondrial DNA (mtDNA) point mutations (A3243G, T8993G/C, A8344G, A1555G, G11778A, G3460A and T14484C) in Chinese, we recruited 1559 sporadic patients suspected of mitochondrial diseases and 206 family members. In suspected patients, 158 cases were detected with one of these eight mtDNA mutations (10.1%). A3243G was the most common mtDNA mutation both in suspected patients (9.4%) and in the relatives (34.2%). In addition, the ratios of A3243G (mutant/wild-type) and A8344G were significantly correlated with the patients’ age of examination. Moreover, in 76 unrelated probands, the ratio of A3243G was correlated well with their seizures and myopathies. [Copyright &y& Elsevier]

Abstract: m.3243A>G mutation in mitochondrial DNA is the most common pathogenic point mutation, causing a variety of phenotypes. To further elucidate its clinical characteristics, we recruited 47 Chinese families carrying m.3243A>G mutation and analyzed their symptoms, disease history, inheritance, and mitochondria-related complications. In the probands, lactic acidosis, myopathy, seizures, short stature, weight loss and hirsutism were the most common clinical features. In their mothers, lactic acidosis, exercise intolerance, short stature and weight loss were the frequent manifestations, and normal phenotype was found in 59.6% mothers. m.3243A>G mutation was detected in 47 probands and 42 mothers. In the probands, the mutation ratio in blood was threefold higher and the ratio in urine was twofold higher than those of their mothers. m.3243A>G mutation ratio in mothers'' urine and in their probands'' blood were weakly correlated. In conclusion, (a) stroke-like episode induced by m.3243A>G mutation may be the symptom predominantly found in older patients; (b) m.3243A>G mutation ratio correlates with the severity of the disease; (c) m.3243A>G mutation ratio in mothers'' urine may correlate to the ratio in blood in their offspring. [Copyright &y& Elsevier]

Ultrafiltration (UF) was implemented as a process upgrade in a full-scale drinking water treatment plant (DWTP) with a scale of 100,000 m3·d−1, and the performance was systematically investigated over seven years of operation. The results showed that the UF system exhibited excellent rejection of particles and improved the removals of organics by 9.0–14.7%. The annual average UF flux decreased from 28.37 to 16.51 L·m−2·h−1, and it was necessary to employ various cleaning approaches at an increasing frequency for maintaining stable operation. Compared to the initial scenario, the total cost per m3 of water for the UF system after 7-year operation increased by 55%. The cost of membrane replacement, energy, waste water and chemicals played a decisive role on operating cost in the lifecycle of the UF system. The content of cations (i.e., Mg, Al, Si, Ca, Mn and Fe), biological metabolites and organic substances in the cake layer increased significantly during long-term UF filtration, which not only aggravated membrane fouling but also affected the organic composition of the drinking water. The excellent integrity of the UF membrane during the 7-year operation was sufficient to prevent breakthrough of the organic substances from metabolic activity of microorganisms and to ensure biological safety of the permeate. Image 1 • The overall performance of UF membrane is evaluated in a 7-year operation period. • UF membrane considerably improved the conventional DWTP in water quality. • The total treatment cost of per m3 of water increased by 55% after 7-year operation. • The presence of microorganisms had a significant effect on UF filtration. • There were abundant LMW biological metabolites organic substances in cake layer. [ABSTRACT FROM AUTHOR]

• A novel low-molecular-weight polysaccharide was obtained from A. Pubescentis roots. • Its structure was elucidated by chemical analyses and NMR for the first time. • DF80-2 can effectively scavenge DPPH, and hydroxyl radicals, and chelate ferrous ions. • The antioxidant activities may be attributed to its special structural features. A novel heteropolysaccharide with about twenty sugar residues named DF80-2 was obtained from Angelica pubescens Maxim. f. biserrata Shan et Yuan root, one of the most widely used traditional Chinese medicines for thousands of years in China. The possible structure of DF80-2 was proposed considering the comprehensive results of physicochemical properties, methylation analysis, and 1D/2D NMR spectroscopy, which showed that its main chain was composed of (1→3)-, and (1→4)-linked-α- d -Glc p , (1→4)-linked-β- d -Gal p , (1→6)-linked-α- d -Man p , and (1→3)-linked-α- l -Ara f , and the branch was present as the α- d -Glc p -(1→3)-β- d -Gal p A disaccharides stretched from O -6 position of (1→4)-linked-α- d -Glc moiety in the main chain. Congo red analysis, scanning electron microscopy and atomic force microscopy showed that DF80-2 possessed a triple helical conformation, and its branched monomers were interlaced with one another forming a regular network structure. DF80-2 exhibited antioxidant activity by effectively scavenging DPPH, and hydroxyl radicals, and chelating ferrous ions. [ABSTRACT FROM AUTHOR]

Background: Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM 237300), an autosomal recessive rare and severe urea cycle disorder, is associated with hyperammonemia and high mortality., Methods: Herein we present 12 genetic variants identified in seven clinically well-characterized Chinese patients with CPS1 deficiency who were admitted to the Children's Medical Center of Peking University First Hospital from September 2014 to August 2023., Results: Seven patients (two male and five female patients including two sisters) experienced symptoms onset between 2 days and 13 years of age, and they were diagnosed with CPS1 deficiency between 2 months and 20 years. Peak blood ammonia levels ranged from 160 to 1,000 µmol/L. Three patients showed early-onset CPS1 deficiency, with only one surviving after treatment with sodium phenylbutyrate, N-carbamoyl-L-glutamate, and liver transplantation at 4 months, showing a favorable outcome. The remaining four patients had late-onset CPS1 deficiency, presenting with mental retardation, psychiatric symptoms, and self-selected low-protein diets. Among the 12 CPS1 variants identified in these patients, 10 were novel, with all patients exhibiting compound heterozygosity for CPS1 mutant alleles. Seven variants (c.149T > C, c.616 A > T, c.1145 C > T, c.1294G > A, c.3029 C > T, c.3503 A > T, and c.3793 C > T) resulted in single amino acid substitutions. Three frameshift variations (c.2493del, c.3067dup, and c.3241del) were identified, leading to enzyme truncation. One mutation (c.3506&#95;3508del) caused an in-frame single amino acid deletion, while another (c.2895 + 2T > C) resulted in aberrant splicing., Conclusions: Except for two known variants, all other variants were identified as novel. No hotspot variants were observed among the patients. Our data contribute to expanding the mutation spectrum of CPS1., (© 2024. The Author(s).)

Background and Aims: To investigate the clinical features, ALDH5A1 gene variations, treatment, and prognosis of patients with succinic semialdehyde dehydrogenase (SSADH) deficiency., Materials and Methods: This retrospective study evaluated the findings in 13 Chinese patients with SSADH deficiency admitted to the Pediatric Department of Peking University First Hospital from September 2013 to September 2023., Results: Thirteen patients (seven male and six female patients; two sibling sisters) had the symptoms aged from 1 month to 1 year. Their urine 4-hydroxybutyrate acid levels were elevated and were accompanied by mildly increased serum lactate levels. Brain magnetic resonance imaging (MRI) showed symmetric abnormal signals in both sides of the globus pallidus and other areas. All 13 patients had psychomotor retardation, with seven showing epileptic seizures. Among the 18 variants of the ALDH5A1 gene identified in these 13 patients, six were previously reported, while 12 were novel variants. Among the 12 novel variants, three (c.85&#95;116del, c.206&#95;222dup, c.762C > G) were pathogenic variants; five (c.427delA, c.515G > A, c.637C > T, c.755G > T, c.1274T > C) were likely pathogenic; and the remaining four (c.454G > C, c.479C > T, c.1480G > A, c.1501G > C) were variants of uncertain significance. The patients received drugs such as L-carnitine, vigabatrin, and taurine, along with symptomatic treatment. Their urine 4-hydroxybutyric acid levels showed variable degrees of reduction., Conclusions: A cohort of 13 cases with early-onset SSADH deficiency was analyzed. Onset of symptoms occurred from 1 month to 1 year of age. Twelve novel variants of the ALDH5A1 gene were identified., (© 2024. The Author(s).)

Background: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China., Methods: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date., Results: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full., Conclusions: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Background: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice., Methods: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline., Results: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory., Conclusions: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.

Objective: To understand the status and related factors of overweight and obesity in children and adolescents aged 6-17 in Yunnan Province., Methods: From 2016 to 2017, 3463 children and adolescents aged 6-17 from 65 primary and secondary schools in 13 counties of Yunnan Province were selected by stratified cluster sampling method for face-to-face questionnaire survey, including 1716 boys and 1747 girls, 2098 elementary school students, 762 middle school students, 603 high school students, of which, 1368 students from urban area and 2095 students from rural area. The questionnaire included information including, weekly consumption of sugary drinks, sweets, puffed food, fruits, vegetables, breakfast, daily activities of moderate or high intensity, school sports, daily hours of playing video games and watching TV, daily sleep and outdoor activities. Height and weight were measured using standard method. SPSS20.0 was used for χ~(2 )test and multivariate Logistic regression analysis., Results: The prevalence of overweight and obesity among children and adolescents aged 6-17 were 8.43%(292/3463) and 6.01%(208/3463) respectively. The overweight rates of male students and female students were 8.45%(145/1716) and 8.41%(147/1747) respectively, and the statistic was significant differently(χ~(2 )=0.001, P&gt;0.05). The overweight rates of urban and rural children and adolescents were 11.99%(164/1368) and 6.11%(128/2095) respectively, and the statistic was significant differently(χ~2=37.04, P&lt;0.01). The overweight rates of primary school, middle school and high school were 7.53%(158/2098), 9.32%(71/762) and 10.45%(63/603) respectively, and the statistic was significant differently(χ~2=6.15, P&lt;0.05). The obesity rates of male and female students were 7.11%(122/1716) and 4.92%(86/1747) respectively, and the statistic was significant differently(χ~2=7.33, P&lt;0.01). The obesity rates of urban and rural children and adolescents were 9.50%(130/1368) and 3.72%(78/2095) respectively, and the statistic was significant differently(χ~2=48.97, P&lt;0.01). The obesity rates of primary school, middle school and high school were 7.67%(161/2098), 3.15%(24/762) and 3.81%(23/603), respectively, and the statistic was significant differently(χ~2=26.48, P&lt;0.01). Multivariate Logistic regression analysis showed that cities(OR=2.025, 95%CI 1.646-2.492) and non-residential schools(OR=1.808, 95%CI 1.470-2.223) were associated with overweight and obesity in children and adolescents, both of which were statistically significant(P&lt;0.05)., Conclusion: The prevalence of overweight and obesity among children and adolescents aged 6-17 in Yunnan Province were high. Urban, non-residential school children and adolescents are more likely to be overweight and obesity.

Background: Propionic acidemia is a severe inherited metabolic disorder, caused by the deficiency of propionyl-CoA carboxylase which encoded by the PCCA and PCCB genes. The aim of the study was to investigate the clinical features and outcomes, molecular epidemiology and phenotype-genotype relationship in Chinese population., Methods: We conducted a retrospective study of 60 Chinese patients diagnosed at Peking University First Hospital from 2007 to 2020. Their clinical and laboratory data were reviewed. The next-generation sequencing was conducted on blood samples from 58 patients., Results: Only 5 (8.3%) patients were identified by newborn screening. In the rest 55 patients, 25 had early-onset (≤ 3 months) disease and 30 had late-onset (> 3 months) disease. Neurological abnormalities were the most frequent complications. Five cases detected by newborn screening had basically normal development. Nine (15%) cases died in our cohort. 24 patients (41.4%) harbored PCCA variants, and 34 (58.6%) harbored PCCB variants. 30 (11 reported and 19 novel) variants in PCCA and 28 (18 reported and 10 novel) variants in PCCB mere identified. c.2002G>A and c.937C>T in PCCA, and c.838dupC in PCCB were the most common variants in this cohort, with the frequency of 13.9% (6/44 alleles), 13.9% (6/44 alleles) and 12.5% (8/64 alleles), respectively. There was no difference in clinical features and outcomes between patients with PCCA and PCCB variants. Certain variants with high frequencies and homozygotes may be associated with early-onset or late-onset propionic acidemia., Conclusions: Although the genotype-phenotype correlation is still unclear, certain variants seemed to be related to early-onset or late-onset propionic acidemia. Our study further delineated the complex clinical manifestations of propionic acidemia and expanded the spectrum of gene variants associated with propionic acidemia., (© 2022. The Author(s).)

Objective: To analyzing the malnutrition status and influencing factors of children under 5 years in Yunnan Province., Methods: Multi-stage stratified sampling used in the national survey was performed. The subjects of the study were 2869 children under 5 years, selected from 13 counties(cities) in Yunnan Province from 2016 to 2017. The contents of the investigation included questionnaire survey and anthropometric measurement. Z-scores were calculated according to WHO growth standards by WHO Anthro V3.2.2 software. Non conditional Logistic regression model was used to analyze the multiple factors. SPSS 20.0 statistical software was used to calculate and analyze the malnutrition rate of children., Results: A total of 2869 children under 5 years old were investigated in Yunnan Province, including 1433 boys(49.95%) and 1436 girls(50.05%). The prevalence of stunting, underweight and wasting of children under 5 years old were 3.46%, 6.37% and 3.42%. Logistic multifactor regression analysis showed that low birth weight(OR=4.368, 95% CI 2.057-9.275), rural area(OR=1.931, 95% CI 1.076-3.462), household use of unsanitary toilets(OR=1.688, 95% CI 1.022-2.790), children without supplemental food(OR=2.000, 95% CI 1.130-3.542) were the most important factors making the child more likely to become malnutrition in 6-23 month age group. Asking children for advice on food selection or cooking(OR=3.570, 95%CI 1.249-10.204) was the most important factors making the child more likely to become malnutrition in 6-23 month age group., Conclusion: The nutritional status of children under 5 years old in Yunnan Province has been improved, but the prevalence of malnutrition is still high.

The outbreak of the COVID-19 pandemic has caused an upsurge economic policy uncertainty (EPU). Study on the time-varying effect of EPU is of substantial implication for the central bank in implementation of monetary policy. To empirically investigate the time-varying effect of EPU, the paper considers the shock of the monetary policy implemented by China's central bank on different economic variables including interest rate, output gap, and inflationary gap using the latent threshold time-varying parameter vector autoregressive model (LT-TVP-VAR Model). Data period is chosen to be January 2015 through April 2021. Our findings show that (i) EPU has a significant threshold effect on the shock of quantitative monetary policy instrument and the shock of price-based monetary policy, and that the two types of policy are positively correlated; (ii) the price-based monetary policy instrument has a significant counter-cyclical effect on both output gap and inflationary gap; (iii) relative to the quantitative monetary policy instrument, the price-based monetary policy instrument has a more significant counter-cyclical effect on output gap; and (iv) a higher level of EPU is associated with a more significant monetary policy effect on output gap and inflationary gap., 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 © 2021 Song, Yang, Yu and Zhao.)

Background: This study investigated the prevalence and related factors of trauma exposure and probable posttraumatic stress disorder (PTSD) in adults from a Chinese community sample., Methods: Participants were 7218 adults recruited from Jiangxi and Hunan provinces in China. Life Events Checklist and Posttraumatic Stress Disorder Checklist for DSM-5 were used to screen lifetime trauma exposure and PTSD symptoms, respectively. Participants' adverse and positive childhood experiences, behavioral inhibition, depression, insomnia, psychotic-like experiences (PLEs) and ADHD symptoms were also measured. Multiple regressions were performed to examine the correlates of PTSD., Results: Approximately 67.1% of participants reported one traumatic event; 27.1% experienced four or more. Participants recruited from private school, male, young age, low socioeconomic status, and poor physical health were associated with more trauma-exposure. The prevalence of PTSD was 2.1% in the total sample and 3.1% among the trauma-exposed. Among participants with PTSD, 53.6% were screened as depression, 54.3% had insomnia, 65.6% had one to three PLEs, 12.6% had four to seven PLEs, and 26.5% were screened as likely ADHD, and 5.3% highly likely ADHD. Younger age, being less educated, poor marriage quality and physical health, more adverse childhood experiences, behavioral inhibition and less positive childhood experiences were associated with increased risk of PTSD among the trauma exposed. After adjustment of these related factors, depression, insomnia, PLEs and ADHD were related to PTSD., Conclusions: PTSD is relatively prevalent among Chinese community population. Childhood experiences, behavioral inhibition, and concurrent mental health account for individual differences in vulnerability to PTSD., (Copyright © 2021. Published by Elsevier B.V.)

Multiple factors, including increasing incidence, poor knowledge of stroke and lack of effective, noninvasive and convenient stroke risk prediction tools, make it more difficult for precautions against stroke in China. Effective prediction models for stroke may assist to establish better risk awareness and management, healthier lifestyle, and lower stroke incidence for people.The China Health and Retirement Longitudinal Survey was the development cohort. Logistic regression was applied to model's development, in which the candidate variables with statistically significant coefficient were included in the prediction model. The area under receiver operating characteristic curve (AUC) and 10-times cross-validation were used for internal validation. Cutoff point of high-risk group was measured by Youden index. The China Health and Nutrition Survey was the validation cohort.The development cohort and the validation cohort included 16557 and 5065 participants, and the incidence density was 358.207/100,000 person-year and 350.701/100,000 person-year, respectively. The model for 2-year new-onset stroke risk prediction included age, hypertension, diabetes, heart disease, and smoking. The AUC and cross-validation AUC were 0.707 (95% confidence interval[CI]: 0.664, 0.750) and the 0.710 (95% CI: 0.650, 0.736). The sensitivity, specificity and accuracy of the cutoff point were 0.774, 0.545, and 0.319. The AUC and cross-validation AUC were 0.800 (95% CI: 0.744, 0.856) and 0.811(95% CI:0.714, 0.847), and the sensitivity, specificity and accuracy of cutoff point being 0.857,0.569, and 0.426 in external validation.A simple prediction tool using 5 noninvasive and easily accessible factors can assist in 2-year new-onset stroke risk prediction in Chinese people over 45 years old, which is believed to be applicable in identifying high-risk individuals and health management in China.

Background: Cobalamin C deficiency (cblC) caused by the MMACHC mutations is the most common type of the disorders of intracellular cobalamin metabolism. While the c.609G > A mutation is most frequent in Chinese cblC patients, its correlation with phenotype has not been delineated. Here we aim to investigate the factors affecting variable phenotypes and outcomes associated with the MMACHC c.609G > A homologous mutation in 149 Chinese cases to have implications for treatment and prevention., Methods: We assessed 149 cblC patients caused by MMACHC c.609G > A homozygous mutation. The clinical manifestations, complications, treatment, and outcomes were evaluated; 120 patients were followed-up till December 2019., Results: Two patients (1.3%) were prenatally diagnosed, treated after birth and consequently showed normal development. In 15 patients (10.1%) detected by newborn screening, 10 were treated at the age of 2 weeks and showed normal development, while the other 5 were treated after onset and showed neurologic disorders. All 132 clinically diagnosed patients (88.6%) developed symptoms at age from few minutes after birth to 72 months. Among them, 101 (76.5%) had early-onset (before the age of 12 months) and 31 (23.5%) had late-onset (after the age of 12 months). Totally 5 patients died and 24 were lost to follow-up. Of the 132 clinical diagnosed patients, 92 (69.7%) presented with developmental delay, 65 (49.2%) had seizures, 37 (28.0%) had anemia, 24 (18.2%) had feeding difficulty, 23 (17.4%) had ocular problems, and 22 (16.7%) had hydrocephalus. Compared with the non-developmental delay group, the onset age, the age at treatment initiation and the time from onset to treatment initiation were later in the developmental delay group. Seizure group showed significantly higher urinary methylmalonic acid concentration. During long-term follow-up, plasma total homocysteine (tHcy) levels were significantly higher in patients in the uncontrolled group than those in the seizure-free group., Conclusions: Most cblC patients caused by MMACHC c.609G > A homozygous mutation showed early-onset. The clinically diagnosed patients usually showed the presence of irreversible brain disorders. Patients treated from the pre-symptomatic stage showed favorable outcomes. Therefore, newborn screening, prenatal diagnosis and early treatment are crucial and the c.609G > A mutant allele should be listed in the pre-pregnancy carrier screening panel in China.

Methylmalonic acidemia (MMA) is the most common organic acidemia in China. This study aimed to characterise the genotypic and phenotypic variabilities, and the molecular epidemiology of Chinese patients with isolated MMA. Patients (n = 301) with isolated MMA were diagnosed by clinical examination, biochemical assays, and genetic analysis. Fifty-eight patients (19.3%) were detected by newborn screening and 243 patients (80.7%) were clinically diagnosed after onset. Clinical onset ranged from the age of 3 days to 23 years (mean age = 1.01 ± 0.15 years). Among 234 MMA patients whose detailed clinical data were available, 170 (72.6%) had early onset disease (before the age of 1 year), and 64 (27.4%) had late-onset disease. The 234 MMA patients manifested with neuropsychiatric impairment (65.4%), haematological abnormality (31.6%), renal damage (8.5%), and metabolic crises (67.1%). Haematological abnormality was significantly more common in early-onset patients than that in late-onset patients. The incidence of metabolic crises was significantly high (P < 0.001) in patients with mut type than those with other types of isolated MMA. Variations (n = 122) were identified in MMUT, MMAA, MMAB, MMADHC, SUCLG1, and SUCLA2, of which 45 were novel. c.729&#95;730insTT was the most frequent MMUT mutation, with a significantly higher frequency in our patients than that in 151 reported European patients. The frequency of c.914T>C in MMUT in our cohort was also higher than that in 151 European patients. MMUT mutations c.729&#95;730insTT and c.914T>C are specific for the Chinese population. Our study expanded the spectrum of phenotypes and genotypes in isolated MMA., (© 2019 SSIEM.)

Background: Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is a rare autosomal recessive disorder that affects the degradation of medium-chain fatty acids. Few cases of MCADD have been documented to date in mainland China., Methods: Medium-chain acyl-coenzyme A dehydrogenase deficiency was diagnosed in six patients (three girls and three boys) from six unrelated Chinese families at ages ranging from 10 days to 3 years old. The diagnosis was confirmed by the identification of a primary biomarker of serum octanoyl-carnitine (C8) and genetic pathogenic mutations., Results: Only two patients were admitted because of vomiting, diarrhea, myasthenia, and coma; the other four patients were diagnosed via the newborn screening process. Six mutations were found in acyl-CoA dehydrogenase medium chain (ACADM). One mutation (c.727C>T) was novel and the others (c.158G>A, c.387+1delG, c.449&#95;452del, c.1045C>T, and c.1085G>A) have been previously reported., Conclusions: Six Chinese cases of MCADD were identified. One novel mutation was found. c.449&#95;452del and c.1085G>A were common mutations in this study., (© 2019 Japan Pediatric Society.)

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.

Cobalamin G (cblG) and cobalamin J (cblJ) defects are rare disorders of cbl metabolism caused by MTR and ABCD4 mutations, respectively. Patients with atypical biochemical features can be missed by current newborn screening using tandem mass spectrometry (MS/MS), in which total homocysteine (tHCY) in dried blood spots (DBS) is not a primary biomarker. Two Chinese patients suspected of cbl defect but missed by newborn screening were studied. Using comprehensive metabolic analyses including MS/MS assay for tHCY in DBS, slightly low methionine in Patient 1, methymalonic aciduria in Patient 2, and homocysteinemia in both patients were detected, and DBS tHCY of two patients were obviously elevated (59.22 μmol/L, 17.75 μmol/L) compared to 140 healthy controls (2.5th-97.5th percentile, 1.05-8.22 μmol/L). Utilizing whole-exome sequencing, we found two novel MTR variants c.871C>T (p.Pro291Ser) and c.1771C>T (p.Arg591*) in Patient 1, and a ABCD4 homozygous variant c.423C>G (p.Asn141Lys) in Patient 2. Our study identified the first cblG patient and cblJ patient in mainland China, and highlighted comprehensive metabolic analyses and genetic tests in patients suspected of cbl defects. It also indicated that supplementary MS/MS assay for tHCY in DBS may be practical for early diagnosis of homocysteinemia, without repeated blood sampling.

There are two genetics complementary groups Cockayne syndrome type A and B (CS-A and CS-B OMIM 216400, 133540), which is a rare autosomal recessive segmental progeroid syndrome. Homozygous or compound heterozygous mutations in the excision repair cross-complementation group 8 gene (ERCC8) result in CS-A, and mutations in ERCC6 result in CS-B. Homozygous ERCC6/ERCC8 mutations also result in UV-sensitive syndrome. In this study, twenty-one Han Chinese patients with CS were investigated to identify mutations in ERCC8/ERCC6, of which thirteen cases with CS-A were identified with the mutations of ERCC8. There are five types mutations of ERCC8 in our study, such as exon 4 rearrangement, c.394&#95;398delTTACA, c.299insA, c.843 + 2 T > C, and c.2 T > A. An estimated frequency of exon 4 rearrangement accounts for 69.23% and c.394&#95;398delTTACA accounts for 11.53% in our cohort. Haplotype analysis revealed that the exon 4 rearrangement and c.394&#95;398delTTACA mutations originated from a common founder in the Chinese population respectively. With the identification of three novel ERCC8 mutations, this study expanded the molecular spectrum of known ERCC8 defects, and furthermore, suggests that the exon 4 rearrangement and c.394&#95;398delTTACA mutations may be a common underlying cause of CS-A in the Chinese population, which is different from that in other populations.

Background: Niemann-Pick disease type A (NPD-A) is a rare autosomal recessive lysosomal storage disorder caused by acid sphingomyelinase deficiency. Only a few cases have been documented in mainland China, and prenatal diagnosis has not been performed to date. In this study, the clinical and laboratory features of four Chinese patients with early-onset NPD-A were summarized., Methods: Four patients with NPD-A were the firstborns of non-consanguineous parents from four unrelated Chinese families. Bone marrow analysis, acid sphingomyelinase assay and genetic studies were performed. SMPD1 gene studies on amniocytes were performed for the prenatal diagnosis of four fetuses from three families., Results: Four patients were admitted at the age of 1-10 months due to jaundice, hepatosplenomegaly and psychomotor retardation. Liver histopathological analysis revealed glucolipid accumulation. Massive foamy histiocytes were found in the bone marrow. Acid sphingomyelinase activities of peripheral blood leukocytes were significantly decreased (4.05-21.9 nmol/h/mg protein, normal range 216.1-950.9 nmol/h/mg protein). Seven novel mutations (c.518-519insT, c.562&#95;563insC, c.792Gdel, c.949G>A, c.1487&#95;1499delACCGTGTGTACCA, c.1495T>C and c.1670T>C) of the SMPD1 gene were identified in four patients. Only one fetus had two mutations of the SMPD1 gene of amniocytes. The results suggested that the fetus was affected by NPD-A. The mother chose artificial abortion. The other three fetuses were not affected by NPD-A. No mutation of the SMPD1 gene was detected in the cultured amniocytes from the mothers. Postnatal genetic analysis and normal development of the three infants confirmed the prenatal diagnosis., Conclusions: Seven novel mutations associated with NPD-A were identified in the Chinese population. Prenatal diagnosis for four fetuses of three families was successfully performed by amniocyte gene analysis., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: Methylmalonic aciduria is the most common organic aciduria in mainland China. Succinate-CoA ligase deficiency causes encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Patients usually present with severe encephalomyopathy, infantile lactic acidosis, which can be fatal, and mild methylmalonic aciduria., Patients and Methods: Three Chinese patients (two boys and one girl) were hospitalized because of severe encephalomyopathy between 7 and 9 months. They presented with severe psychomotor retardation, hypotonia, dystonia, athetoid movements, seizures, feeding problems and failure to thrive. Mild elevated urine methylmalonic acid and blood propionylcarnitine indicated methylmalonic aciduria. Gene capture and high-throughput genomic sequencing was carried out., Results: Five novel mutations in SUCLG1 were identified in these patients: c.550G>A (p.G184S) in exon 5, c.751C>T (p.G251S) in exon 7, c.809A>C (p.L270W) in exon 7, c.961C>G (p.A321P) in exon 8 and c.826-2A>G (Splicing) in exon 9. Significant depletion of mtDNA was not observed in the peripheral leukocytes of the three patients in spite of mild decreasing of mitochondrial respiratory chain complex I in two patients and complex V in one patient. After treatment with cobalamin, calcium folinate, L-carnitine, vitamin B1, C, and coenzyme Q10, and nutrition intervention, the patients improved., Conclusions: Succinate-CoA ligase deficiency due to SUCLG1 mutations is a rare cause of methylmalonic aciduria. Biochemical and gene studies are keys for the differential diagnoses. Three Chinese patients with mild methylmalonic aciduria were genetically diagnosed using high-throughput genomic sequencing. Five novel pathogenic mutations in SUCLG1 were identified., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare mitochondrial fatty acid β-oxidation disorder. We aimed to explore the clinical, biochemical, and genetic findings, treatments and outcomes in eight Chinese VLCADD patients., Methods: Eight patients from six unrelated Chinese families with symptomatic VLCADD were diagnosed in the past 4 years. The clinical features and ACADVL gene mutations were analyzed., Results: One patient underwent newborn screening and has been treated timely, she hardly had any symptoms. The remaining seven patients were found because of edema, diarrhea, coma, liver damage and psychomotor retardation. Seven patients had fatty liver. Five had myopathy. All patients had elevated blood tetradecanoylcarnitine. Nine heterozygous mutations of the ACADVL gene were found. Three (c.1102C > T, c.1795G > A and IVS10, +6T > A) were novel. Seven patients completely recovered after treatment. One patient died before diagnosis due to cardiomyopathy. His mother underwent amniocentesis for prenatal diagnosis. The fetus had the same gene mutation of the proband and markedly elevated tetradecanoylcarnitine in amniotic fluid. The boy has been treated after birth and he is healthy now., Conclusions: Dietary treatment usually leads to good outcomes to VLCADD patients. Amniocytes ACADVL mutations and amniotic fluid tetradecanoylcarnitine analysis are useful for the prenatal diagnosis., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: Combined methylmalonic aciduria (MMA) and homocystinuria, cblC type, is the most common MMA in Mainland China. Its clinical spectrum varies from severe neonatal-onset forms with brain injury and high mortality to milder forms with late onset. Timely diagnosis and adequate treatment greatly improve the prognosis. In the past 15 years, many Chinese patients with this condition have achieved favorable treatment outcomes, and some of them have reached childbearing age. Here, we report the first case of Chinese woman with cblC undergoing a successful pregnancy and delivering a healthy boy., Methods: A patient of late-onset cblC, who achieved successful pregnancy and delivery of a healthy boy, was enrolled in our studies. The patient and her disease characteristics were analyzed, including age at onset, age at diagnosis, clinical presentation, clinical classification, family history, laboratory findings and MMACHC gene mutation., Results: Our patient presented mild neurological symptoms at the age of 15 years. She had the compound heterozygous mutations, c.315C>G and c.482G>A, on the MMACHC gene. After long-term treatment with cobalamin, calcium folinate, l-carnitine and betaine, along with normal diet, she recovered completely. At age 23, she visited us for genetic counseling and fetal evaluation at 15 weeks of gestation. Her general condition and the fetal growth were normal. At 20 weeks of gestation, intramuscular cobalamin was changed to pure hydroxocobalamin (1 mg, every other day) because of markedly elevated urine MMA and plasma total homocysteine. In addition, the dosages of l-carnitine (1 g, p.o., tds), folic acid (5 mg, p.o., tds) and betaine (1 g, p.o., tds) were increased. Protein intake was not restricted., Conclusions: This is the first report of a Chinese woman with cblC, undergoing a successful pregnancy and delivering a healthy baby at term. The favorable outcome of the patient and her fetus should owe much to the mild phenotype of her disease., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder caused by glutaryl-CoA dehydrogenase deficiency due to GCDH gene mutations. In this study, the clinical presentation and molecular aspects of 23 Chinese patients (11 males and 12 females) were investigated., Methods: All patients were diagnosed by elevated urinary glutaric acid and GCDH gene analysis. Protein-restricted diet supplemented with special formula, l-carnitine and GABA analog were initialed after diagnosis. The clinical and biochemical features were analyzed. Mutational analysis of GCDH was conducted., Results: Clinical manifestations of 23 patients varied from asymptomatic to severe encephalopathy, with notable phenotypic differences between siblings with the same mutations. One case was detected by newborn screening, while 22 Cases were diagnosed between the ages of 5 months and 51 years. 29 mutations in GCDH were identified. Among them, 11 were novel, including seven missense mutations (c.406G > T, C.416C > G, c.442G > A, c.640A > G, c.901G > A, c.979G > A, and c.1207C > T), three frameshift mutations (c.873delC, c.1172-1173insT and c.1282-1285ins71) and one nonsense mutation (c.411C > G). In exon 5, c.553G > A and c.148T > C were found in four alleles (8.7%) and three alleles (6.5%) of the patients, respectively., Conclusions: In 23 Chinese patients with GA1, 11 novel GCDH mutations were identified. This may indicate that the genetic profiles of Chinese patients are different from those of other populations., Synopsis: 23 Chinese GA1 patients with varied clinical manifestations have been reported. 11 novel mutations in their GCDH gene were identified, indicating that the genetic profiles of Chinese GA1 patients differ from those of other populations., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: National coverage of neonatal screening for hyperphenylalaninaemia (HPA) in China is still low and tests to differentiate causes of HPA are not performed in many centres. This study aimed to describe the demographics, geographic distribution, diagnosis, treatment and clinical outcomes of treatment, including intellectual development, in patients with tetrahydrobiopterin (BH4) deficiency in mainland China., Methods: This was a retrospective, multicentre, chart review in patients with BH4 deficiency across mainland China born 1985-2010., Results: Two hundred fifty six patients were included; 59.9 % (267/446) of parents were from eastern China. Median (interquartile range) age at diagnosis decreased from 12.0 (5.5, 102.0) months to 2.0 (1.0, 3.5) months in patients born 1985-1999 (n = 28) and 2005-2010 (n = 152), respectively. 6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency was the primary cause of BH4 deficiency (96.0 %); four hotspot mutations accounted for 76.6 % of PTS gene mutations; two novel variants in the QDPR gene were identified. Most patients (83.6 %) received treatment with BH4, L-dopa, 5-hydroxytryptophan and/or diet therapy. Target blood Phe concentration was confirmed at 88.9 % of visits; median (Q1, Q3) blood Phe concentration was 106.8 (73.0, 120.0) μmol/L during therapy and 117.0 (67.1, 120.0) μmol/L at last visit. Median (Q1, Q3) WISC IQ score was 80.0 (69.0, 90.0) in 33 patients. DQ scores were within normal range (≥85) for 37/59 (62.7 %) patients. Physical development indicators were within normal ranges. Treatment-related adverse events, reported in 20/256 (7.8 %) patients, were mild-to-moderate in severity., Conclusion: This study provides valuable information on the current and historical situation of BH4 deficiency in mainland China.

The most common inborn error of cobalamin (cbl) metabolism in China is the cblC type characterized by combined methylmalonic acidemia and hyperhomocysteinemia. The clinical presentation is relatively nonspecific, such as feeding difficulty, recurrent vomiting, hypotonia, lethargy, seizures, progressive developmental delay, and mental retardation, together with anemia and metabolic acidosis. More specific biochemical findings include high levels of propionylcarnitine (C3), free carnitine (C3/C0), and acetylcarnitine (C3/C2) measured by tandem mass spectrometry (MS/MS), elevation of methylmalonic acid (MMA) measured by gas chromatography-mass spectrometry (GC-MS), and increased total homocysteine with normal or decreased methionine. We report on 50 Chinese patients with combined methylmalonic acidemia and hyperhomocysteinemia. Forty-six belonged to the cblC complementation group. Mutation analysis of the MMACHC gene was performed to characterize the mutational spectrum of cblC deficiency, and 17 different mutations were found. Most were clustered in exons 3 and 4, accounting for 91.3% of all mutant alleles. Two mutations were novel, namely, c.315 C>G (p.Y105X) and c.470 G>C(p.W157S). In terms of genotype-phenotype correlation, the c.609 G>A mutation was associated with early-onset disease when homozygous. Unlike previous reports from other populations, c.609 G>A (p.W203X) was the most frequent cblC mutation detected in our study of Chinese patients, affecting 51 of 92 MMACHC alleles (55.4%). The high prevalence of this nonsense mutation could have potential therapeutic significance for Chinese cblC patients. Besides traditional approaches consisting of hydroxocobalamin injections, carnitine, betaine, and protein restriction, novel drugs that target premature termination codons may have a role in the future.

Background: Subtelomeric imbalance is widely accepted as related to developmental delay/mental retardation (DD/MR). Fine mapping of aberrations in gene-enriched subtelomeric regions provides essential clues for localizing critical regions, and provides a strategy for identifying new candidate genes. To date, no large-scale study has been conducted on subtelomeric aberrations in DD/MR patients in mainland China., Methods: This study included 451 Chinese children with moderate to severe clinically unexplained DD/MR. The subtelomere-MLPA (multiplex ligation dependent probe amplification) and Affymetrix human SNP array 6.0 were used to determine the subtelomeric copy number variations. The exact size and the breakpoint of each identified aberration were well defined., Results: The submicroscopic subtelomeric aberrations were identified in 23 patients, with a detection rate of 5.1%. 16 patients had simple deletions, 2 had simple duplications and 5 with both deletions and duplications. The deletions involved 14 different subtelomeric regions (1p, 2p, 4p, 6p, 7p, 7q, 8p, 9p, 10p, 11q, 14q, 15q, 16p and 22q), and duplications involved 7 subtelomeric regions (3q, 4p, 6q, 7p, 8p, 12p and 22q). Of all the subtelomeric aberrations found in Chinese subjects, the most common was 4p16.3 deletion. The sizes of the deletions varied from 0.6 Mb to 12 Mb, with 5-143 genes inside. Duplicated regions were 0.26 Mb to 11 Mb, with 6-202 genes inside. In this study, four deleted subtelomeric regions and one duplicated region were smaller than any other previously reported, specifically the deletions in 11q25, 8p23.3, 7q36.3, 14q32.33, and the duplication in 22q13. Candidate genes inside each region were proposed., Conclusions: Submicroscopic subtelomeric aberrations were detected in 5.1% of Chinese children with clinically unexplained DD/MR. Four deleted subtelomeric regions and one duplicated region found in this study were smaller than any previously reported, which will be helpful for further defining the candidate dosage sensitive gene associated with DD/MR.

Objective: To investigate the MUT gene mutations in patients with methylmalonic acidemia (MMA), and analyze the genotype-phenotype correlation in patients with methylmalonyl-CoA mutase deficiency., Methods: The diagnosis of the disease mainly depends on the measurement of C3 (acylcarnitine), C3/C0 (free carnitine) and C3/C2 (acetylcarnitine) in the blood by tandem mass spectrometry, the detection of methylmalonic acid in the urine by gas-chromatography mass spectrometry, the determination of total homocysteine in the serum, and the loading test of vitamin B(12). The entire coding region of the MUT gene was screened by PCR combined with direct DNA sequencing in 21 isolated MMA patients. Novel mutations were identified by restriction fragment length polymorphism (RFLP) and sequence analysis in 100 controls., Results: Seventeen MUT gene mutations were detected in 14 of the 21 patients, among them 8 mutations were novel, and R108H, D244LfsX39 and G544X were more frequent, with the frequencies of 9.5%, 7.1% and 9.5%, respectively. Most mutations were missense mutations (64.7%), and majority of them were in exons 2 and 3 (55.6%). Ten out of the 14 patients with MUT gene mutations had early-onset disease, while one case had late-onset disease, and the remaining 3 cases were detected by newborn screening. In addition, 11 of these 14 patients did not respond to vitamin B(12)., Conclusion: This study revealed partial MUT gene mutation spectrum in Chinese patients with isolated MMA. The patients carrying MUT mutations often had early-onset disease, and most of them were VitB(12)- non-responsive.

From June 1998 to May 2007, 9566 urine samples were collected from patients with psychomotor deficits, seizures, vomiting and unconsciousness in Peking University First Hospital. Their urine organic acids profiles were analysed using gas chromatography - mass spectrometry (GCMS), GCMS solution and Inborn Errors of Metabolism Screening System software. In all patients, blood acylcarnitines were analysed using tandem mass spectrometry. One hundred and sixty-eight patients (1.76%) with organic acidurias were detected. Among them, 116 (116/ 168, 69.0%) had methylmalonic aciduria, 63 (54.3%) of these 116 patients had methylmalonic aciduria combined with homocysteinemia. Sixteen (9.5%) of those patients detected with organic acidurias had propionic aciduria, and 15 (8.9%) had multiple carboxylase deficiency. Seven (4.2%) had glutaric aciduria type 1. After dietary treatment, medicine and rehabilitation, clinical improvements were observed in more than half of the patients. Twenty-eight of the 168 patients (16.7%) recovered and led a normal life. The method of urine organic acid analysis by gas chromatography - mass spectrometry and blood acylcarnitines analysis by tandem mass spectrometry have been established and applied successfully in China, namely Beijing, Shanghai, Wuhan and Guangzhou. The prognoses of Chinese patients with organic acidurias have also improved significantly.