Telomere length and micronuclei trajectories in APP/PS1 mouse model of Alzheimer's disease: Correlating with cognitive impairment and brain amyloidosis in a sexually dimorphic manner.

Although studies have demonstrated that genome instability is accumulated in patients with Alzheimer's disease (AD), the specific types of genome instability linked to AD pathogenesis remain poorly understood. Here, we report the first characterization of the age- and sex-related trajectories of telomere length (TL) and micronuclei in APP/PS1 mice model and wild-type (WT) controls (C57BL/6). TL was measured in brain (prefrontal cortex, cerebellum, pituitary gland, and hippocampus), colon and skin, and MN was measured in bone marrow in 6- to 14-month-old mice.

Features of liver injury in 138 Chinese patients with NICCD.

Objectives: To find biochemical and molecular markers can assist in identifying serious liver damage of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) patients.

Methods: 138 patients under 13 days to 1.1 year old diagnosed of NICCD in our center from 2004 to 2020.

Modified nusinersen intrathecal injection method: inclusion of a septal needle-free closed infusion connector.

Objective: Nusinersen, an extremely expensive biologic drug (around 100,000 US$ per dose) that needs to be administered intrathecally, is approved for the treatment of 5q-spinal muscular atrophy (SMA). Because of the low muscle tone of the back muscles of pediatric SMA patients, especially type 1 SMA patients, the safe, effective, and fast execution of sheath injection is needed. Therefore, a modified intrathecal injection method was developed accordingly.

Presenilin-1, mutated in familial Alzheimer's disease, maintains genome stability via a γ-secretase dependent way.

Mutations in Presenilin-1 (PS1) account for over 80 % mutations linked to familial Alzheimer's disease (AD). However, the mechanisms of action of PS1 mutations in causing familial AD are not fully understood, limiting opportunities to develop targeted disease-modifying therapies for individuals carrying PS1 mutation. To gain more comprehensive insights into the impact of PS1 mutations on genome stability, we knocked down PS1 in SH-SY5Y, HMC3 and A549 cells.

High-dose metformin induces a low-glucose dependent genotoxic stress.

Epidemiological studies have demonstrated that metformin (a cornerstone of diabetes treatment) has anticancer activity, but the underlying mechanism remains elusive. We aimed to investigate whether metformin elicits anticancer activity via increasing genotoxic stress, a state of increased genome damage that becomes tumor-suppressing if it goes beyond an intolerable threshold. We found that metformin (1-16 mM) suppressed proliferation and colony formation in a panel of cancer cell lines (HeLa, A375, A549 and QGY).

A very rare case report of glycogen storage disease type IXc with novel PHKG2 variants.

Background: Pathogenic mutations in the PHKG2 are associated with a very rare disease-glycogen storage disease IXc (GSD-IXc)-and are characterized by severe liver disease.

Case Presentation: Here, we report a patient with jaundice, hypoglycaemia, growth retardation, progressive increase in liver transaminase and prominent hepatomegaly from the neonatal period. Genetic testing revealed two novel, previously unreported PHKG2 mutations (F233S and R320DfsX5).

Glucose-6-Phosphate dehydrogenase deficiency associated hemolysis in a cohort of new onset type 1 diabetes children in Guangdong province, China.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, with a high prevalence in Guangdong, China. The purpose of this study was to explore the characteristics of newly diagnosed type 1 diabetes (T1D) patients with G6PD deficiency in a cohort of Chinese children and to investigate the relationship between the diabetic ketoacidosis (DKA) and hemolysis due to G6PD deficiency in these patients.

Methods: A total of 503 newly diagnosed T1D children aged 6 months-18 years were collected and their G6PD enzyme activity were measured.

A ruptured giant mediastinal mature teratoma mimicking an encapsulated empyema.

A female patient with a right-sided encapsulated pleural effusion was misdiagnosed preoperatively as having an encapsulated empyema. However, a giant mass in the anterior mediastinum was found via thoracoscopy, and a mature teratoma was detected based on the pathological result. Herein we report this case and provide lessons for cardiothoracic surgeons.

Clinical Characteristics of Elderly Patients with COVID-19 in Hunan Province, China: A Multicenter, Retrospective Study.

Background: The aim of this study was to analyze and summarize the clinical characteristics of elderly patients with coronavirus disease 2019 (COVID-19) and compare the differences of young-old patients (60-74 years old) and old-old patients (≥75 years old).

Methods: In thisretrospective, multicenter study, the medical records of elderly patients who were diagnosed with COVID-19 in Hunan province, China, from January 21 to February 19, 2020 were reviewed. The characteristics of young-old patients and old-old patients were compared.

Novel mutations in a Chinese family with two patients with succinic semialdehyde dehydrogenase deficiency.

A considerable proportion of pediatric disease burden is mainly caused by inborn errors of metabolism. Succinic semi-aldehyde dehydrogenase (SSADH) deficiency is an unusual disorder of the gamma-aminobutyric acid metabolism. Till date, very few cases have been reported in China.

Simultaneous quantification of 48 plasma amino acids by liquid chromatography-tandem mass spectrometry to investigate urea cycle disorders.

Urea cycle disorders (UCD) are inborn errors of ammonia detoxification in which early diagnosis and treatment are critical to prevent metabolic emergencies. Unfortunately, the diagnosis was often and pronounced delayed. To improve diagnosis, we developed herein a liquid chromatography-tandem mass spectrometry method to investigate the disturbance of amino acid profile caused by UCD.

Clinical features, molecular characteristics, and treatments of a Chinese girl with sitosterolemia: A case report and literature review.

Sitosterolemia is a rare autosomal recessive disease characterized by a significant increase in blood plant sterol levels. Clinical manifestations usually include xanthomas, hypercholesterolemia,premature atherosclerosis and hematological abnormalities. We report here a sitosterolemia patient who presented with multiple xanthomas and profound hypercholesterolemia since 3 years old.

Genetic analysis of 63 Chinese patients with mucopolysaccharidosis type II: Functional characterization of seven novel IDS variants.

Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal storage disorder resulting from the deficiency of the enzyme iduronate-2-sulfatase (IDS).This study described the molecular characteristics of 63 Chinese children with MPS II and investigated functional characterization of seven novel IDS variants. We analyzed mutations in the IDS gene of 63 children with MPS II.

Early prenatal diagnosis of lysosomal storage disorders by enzymatic and molecular analysis.

Objective: To report the 4-year experience of early prenatal diagnosis of lysosomal storage disorders (LSDs) at a center in mainland China.

Method: Forty-seven pregnancies affected with LSDs were assed using enzymes and/or molecular studies. Prenatal studies were performed on 43 uncultured chorionic villi (CV) samples, two amniotic fluid samples, and two umbilical cord blood samples.

Genetic and clinical characteristics of Chinese children with Glucokinase-maturity-onset diabetes of the young (GCK-MODY).

Background: There is scarcity of information on the clinical features and genetics of glucokinase-maturity-onset diabetes of the young (GCK-MODY) in China. The aim of the study was to investigate the clinical and molecular characteristics of Chinese children with GCK-MODY.

Methods: Eleven children with asymptomatic hyperglycemia and clinically suspected GCK-MODY were identified from the database of children with diabetes in the biggest children's hospital in South China.

Early transition from insulin to sulfonylureas in neonatal diabetes and follow-up: Experience from China.

Background: Sulfonylurea therapy can improve glycemic control and ameliorate neurodevelopmental outcomes in patients suffering from neonatal diabetes mellitus (NDM) with KCNJ11 or ABCC8 mutations. As genetic testing results are often delayed, it remains controversial whether sulfonylurea treatment should be attempted immediately at diagnosis or doctors should await genetic confirmation.

Objective: This study aimed to investigate the effectiveness and safety of sulfonylurea therapy in Chinese NDM patients during infancy before genetic testing results were available.

Brain abnormalities in fucosidosis: transplantation or supportive therapy?

Fucosidosis is a rare lysosomal storage disease caused by α-fucosidase deficiency, which leads to progressive neurological deterioration and death. Hematopoietic stem cell transplantation is the best curative therapy if performed during the early stages of disease. We report two fucosidosis patients with brain abnormalities and the challenge faced in their management.

Clinical, biochemical, neuroimaging and molecular findings of X-linked Adrenoleukodystrophy patients in South China.

X-linked adrenoleukodystrophy is a common X-linked recessive peroxisomal disorder caused by the mutations in the ABCD1 gene. In this study, we analyzed 19 male patients and 9 female carriers with X-linked adrenoleukodystrophy in South China. By sequencing the ABCD1 gene, 13 different mutations were identified, including 7 novel mutations, and 6 known mutations, and 1 reported polymorphism.

Combination of a Haploidentical Stem Cell Transplant With Umbilical Cord Blood for Cerebral X-Linked Adrenoleukodystrophy.

Background: Childhood cerebral X-linked adrenoleukodystrophy is a rapidly progressive neurodegenerative disorder that affects central nervous system myelin and the adrenal cortex. Hematopoietic stem cell transplantation is the best available curative therapy if performed during the early stages of disease. Only 30% of patients who might benefit from a hematopoietic stem cell transplant will have a full human leukocyte antigen-matched donor, which is considered to be the best choice.