Humans ; Fibrinogen ; Liver/pathology* ; Liver Diseases/pathology* ; Metabolic Diseases/pathology*

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.
Child ; Child, Preschool ; China ; Female ; Fibrinogen/chemistry* ; Humans ; Liver/pathology* ; Liver Diseases/pathology* ; Male ; Metabolic Diseases/pathology* ; Retrospective Studies

The expression or dysfunction of long non-coding RNAs (lncRNAs) is closely related to various hereditary diseases, autoimmune diseases, metabolic diseases and tumors. LncRNAs were also recently recognized as functional regulators of fibrosis, which is a secondary process in many of these diseases and a primary pathology in fibrosis diseases. We review the latest findings on lncRNAs in fibrosis diseases of the liver, myocardium, kidney, lung and peritoneum. We also discuss the potential of disease-related lncRNAs as therapeutic targets for the clinical treatment of human fibrosis diseases.
Autoimmune Diseases ; Fibrosis ; Genetic Diseases, Inborn ; Humans ; Kidney ; Liver ; Lung ; Metabolic Diseases ; Myocardium ; Pathology ; Peritoneum ; RNA, Long Noncoding

Taurine is an abundant, β-amino acid with diverse cytoprotective activity. In some species, taurine is an essential nutrient but in man it is considered a semi-essential nutrient, although cells lacking taurine show major pathology. These findings have spurred interest in the potential use of taurine as a therapeutic agent. The discovery that taurine is an effective therapy against congestive heart failure led to the study of taurine as a therapeutic agent against other disease conditions. Today, taurine has been approved for the treatment of congestive heart failure in Japan and shows promise in the treatment of several other diseases. The present review summarizes studies supporting a role of taurine in the treatment of diseases of muscle, the central nervous system, and the cardiovascular system. In addition, taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis. The review also addresses the functions of taurine (regulation of antioxidation, energy metabolism, gene expression, ER stress, neuromodulation, quality control and calcium homeostasis) underlying these therapeutic actions.
Acidosis, Lactic ; Arthritis ; Brain Diseases ; Calcium ; Cardiovascular System ; Central Nervous System ; Cytoprotection ; Energy Metabolism ; Gene Expression ; Heart Failure ; Japan ; MELAS Syndrome ; Metabolic Diseases ; Mitochondrial Diseases ; Neurodegenerative Diseases ; Pathology ; Quality Control ; Taurine*

Animal models have been used to elucidate the pathophysiology of varying diseases and to provide insight into potential targets for therapeutic intervention. Although alternatives to animal testing have been proposed to help overcome potential drawbacks related to animal experiments and avoid ethical issues, their use remains vital for the testing of new drug candidates and to identify the most effective strategies for therapeutic intervention. Particularly, the study of metabolic diseases requires the use of animal models to monitor whole-body physiology. In line with this, the National Institute of Food and Drug Safety Evaluation (NIFDS) in Korea has established their own animal strains to help evaluate both efficacy and safety during new drug development. The objective of this study was to characterize the response of C57BL/6NKorl mice from the NIFDS compared with that of other mice originating from the USA and Japan in a chemical-induced diabetic condition. Multiple low-dose treatments with streptozotocin were used to generate a type-1 diabetic animal model which is closely linked to the known clinical pathology of this disease. There were no significantly different responses observed between the varying streptozotocin-induced type-1 diabetic models tested in this study. When comparing control and diabetic mice, increases in liver weight and disturbances in serum amino acids levels of diabetic mice were most remarkable. Although the relationship between type-1 diabetes and BCAA has not been elucidated in this study, the results, which reveal a characteristic increase in diabetic mice of all origins are considered worthy of further study.
Amino Acids ; Amino Acids, Branched-Chain ; Animal Experimentation ; Animal Testing Alternatives ; Animals ; Ethics ; Japan ; Korea ; Liver ; Metabolic Diseases ; Metabolomics* ; Mice* ; Models, Animal ; Pathology, Clinical ; Physiology ; Streptozocin

The emerging endoscopic technologies are proved to be effective treatments for obesity in selected patients and to offer the potential advantages of reduced invasiveness, reversibility and repeatability. From the view of operation principle, endoscopic technologies can be classified as restrictive procedure, malabsorption procedure and endoscopic revision of gastric bypass. Restrictive procedures include intragastric balloon, aspiration therapy, endoscopic sleeve gastroplasty (ESG) and transoral gastroplasty. Intragastric balloon employs space occupying, volume restriction and satiety mechanisms, which is superior to drugs and lifestyle change, but shorter than sleeve and bypass surgery. Aspiration therapy is similar to standard percutaneous endoscopic gastrostomy, while there are no available data regarding the obesity and metabolic improvement. Compared with traditional bariatric surgery, ESG does not excise gastric tissue with less complications and without weight regain, but it can not be used as an independent operation still now. Transoral gastroplasty is rarely applied clinically whose efficacy and long-term complications need further studies. Malabsorption surgery includes endoscopic duodenojejunal bypass sleeve (EDJBS) and endoscopic gastroduodenojejunal bypass sleeve(EGDJBS). EDJBS may have the similar mechanism like bypass reducing the blood glucose. Even with obvious effect of weight loss, EDJBS has high morbidity of complications and requirements of the skilled operators. EGDJBS, which imitates bypass anatomy changes and belongs to the mixed operation, should be superior to the above procedures in reducing weight theoretically, but due to the lack of clinical data, its short-term and long-term efficacy still need further clinical observation. As compared to the complexity and risks associated with telescopic surgical revision, endoscopic suturing has been confirmed as less invasive and safer for stomal revisions, while its long-term efficacy of reducing weight and improvement of diabetes are not yet clear. Even if long-term efficacy of reducing weight and morbidity of complication in endoscopic bariatric surgery are still indefinite, and clinical trial researches of large sample and long-term follow-up are absent, with the development of endoscopic skill and the gradual clinical application, endoscopic bariatric surgery will provide a new option for the patients of obesity and metabolic diseases.
Bariatric Surgery ; adverse effects ; methods ; statistics & numerical data ; trends ; Disease Management ; Endoscopy ; adverse effects ; methods ; statistics & numerical data ; Gastric Balloon ; statistics & numerical data ; Gastric Bypass ; adverse effects ; methods ; statistics & numerical data ; Gastroplasty ; adverse effects ; methods ; statistics & numerical data ; Humans ; Metabolic Diseases ; surgery ; Obesity ; surgery ; Reoperation ; adverse effects ; methods ; statistics & numerical data ; Surgical Stomas ; pathology ; statistics & numerical data ; Treatment Outcome ; Weight Loss

OBJECTIVETo investigate the effect of glutaryl-CoA dehydrogenase (GCDH) gene silencing and accumulation of lysine metabolites on the viability of hepatocytes.

METHODSBRL cells were divided into normal control group, negative control group, and GCDH silencing group. The shRNA lentiviral vector for silencing GCDH gene was constructed, and the BRL hepatocytes in the GCDH silencing group and the negative control group were infected with this lentivirus and negative control virus respectively, and then cultured in a medium containing 5 mmol/L lysine. Immunofluorescence assay was used to measure the infection efficiency of lentivirus. Western blot was used to measure the expression of GCDH protein. MTT assay was used to evaluate cell viability. Hoechest33342 staining was used to measure cell apoptosis. Western blot was used to measure the expression of Caspase-3, an index of cell apoptosis.

RESULTSThe lentivirus constructed effectively silenced the GCDH gene in hepatocytes (P<0.01). MTT assay and Hoechest 33342 staining showed no significant differences in cell viability and apoptosis between groups (P>0.05). There was also no significant difference in the expression of Caspase-3 protein between groups (P>0.05).

CONCLUSIONSGCDH gene silencing and accumulation of lysine metabolites may not cause marked hepatocyte injury.

Amino Acid Metabolism, Inborn Errors ; pathology ; therapy ; Animals ; Apoptosis ; Brain Diseases, Metabolic ; pathology ; therapy ; Caspase 3 ; metabolism ; Cell Survival ; Cells, Cultured ; Fluorescent Antibody Technique ; Gene Silencing ; Glutaryl-CoA Dehydrogenase ; deficiency ; genetics ; Hepatocytes ; pathology ; Lysine ; metabolism ; Rats

OBJECTIVETo investigate the influencing factors and pathogenesis of osteopenia in the patients with hemophilia.

METHODSTwenty-three patients with hemophilia were admitted in the hospital affiliated to North China University of Science and technology from March to August 2015, including 13 severe cases, 10 mild and moderate cases. All the patients accepted the detection of serum I collagen cross-linking N terminal peptide (NTX I), osteoprotegerin (OPG), bone alkaline phosphatase (BALP), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) and transforming growth factor-β1 (TGF-β1), the score scale of activity ability was recorded according to the criteria published by the U.S. Center for disease prevention and control in 2002, and 21 patients received the measurement of bone mineral density. According to the World Health Organization (WHO) definition, the clinical significance of bone mineral density (BMD) was assessed by measuring the Z level.

RESULTSZ level>-2 was recorded in 10 cases, Z≤-2 was recorded in 11 cases; the levels of body mass index (BMI) and human bone alkaline phosphatase (BALP) reflecting bone formation in 11 cases (Z≤-2) were lower than there in 10 cases (Z>-2) (P<0.05); the levels of BALP (r=0.489, P<0.05), IGF (r=0.538, P<0.05) and BMI (r=0.572, P<0.01) positively correlated significantly with BMD (P<0.05); the levels of bFGF (r=0.570, P<0.01) and OPG (r=0.505, P<0.05) positively correlated with NTX I, indicating bone destruction (P<0.05); the score of activity ability of severe patients was significantly lower than that of mild and moderate cases (P<0.05), BMD levels of these 2 groups were not statistically different (P>0.05).

CONCLUSIONThe BMD level does not correlate with the clinial grouping of hemophilia, the low body mass index may be a risk factor for bone lose; the mechanism of hemophilia patient's bone lose may be related with the decrease of osteogenic activity, the IGF can prevent bone lose in hemophilia, the bFGF and OPG can promote bone metabolism of the patients with hemophilia.

Alkaline Phosphatase ; metabolism ; Biomarkers ; Bone Density ; Bone Diseases, Metabolic ; pathology ; Bone and Bones ; pathology ; Collagen Type I ; metabolism ; Fibroblast Growth Factor 2 ; metabolism ; Hemophilia A ; pathology ; Humans ; Osteogenesis ; Osteoprotegerin ; metabolism ; Peptides ; metabolism ; Somatomedins ; metabolism ; Transforming Growth Factor beta1 ; metabolism

Any medical diagnosis should take a multimodal approach, especially those involving tumour-like conditions, as entities that mimic neoplasms have overlapping features and may present detrimental outcomes if they are underdiagnosed. These case reports present diagnostic pitfalls resulting from overdependence on a single diagnostic parameter for three musculoskeletal neoplasm mimics: brown tumour (BT) that was mistaken for giant cell tumour (GCT), methicillin-resistant Staphylococcus aureus osteomyelitis mistaken for osteosarcoma and a pseudoaneurysm mistaken for a soft tissue sarcoma. Literature reviews revealed five reports of BT simulating GCT, four reports of osteomyelitis mimicking osteosarcoma and five reports of a pseudoaneurysm imitating a soft tissue sarcoma. Our findings highlight the therapeutic dilemmas that arise with musculoskeletal mimics, as well as the importance of thorough investigation to distinguish mimickers from true neoplasms.
Adult ; Aneurysm, False ; diagnosis ; Biopsy ; Bone Diseases ; diagnosis ; Bone Diseases, Metabolic ; diagnosis ; Bone Neoplasms ; diagnosis ; Cell Proliferation ; Diagnosis, Differential ; Diagnostic Errors ; prevention & control ; Female ; Giant Cell Tumors ; diagnosis ; Humans ; Hyperparathyroidism ; complications ; Leukocytosis ; diagnosis ; Male ; Methicillin-Resistant Staphylococcus aureus ; Middle Aged ; Neoplasms ; diagnosis ; microbiology ; Osteomyelitis ; diagnosis ; microbiology ; Osteosarcoma ; diagnosis ; Sarcoma ; diagnosis ; Soft Tissue Neoplasms ; diagnosis ; Tibia ; pathology

OBJECTIVETo investigate the clinical, biochemical and genetic profiles of 28 Chinese patients with glutaric aciduria type 1.

METHODTwenty-eight patients with glutaric aciduria type 1 seen in the Department of Pediatrics, Peking University First Hospital from July 2003 to October 2013 were studied. The data of clinical course, laboratory examinations, cranial MRI and GCDH gene mutations of the patients were analyzed.

RESULT(1) Three cases were detected by newborn screening, and the other patients were diagnosed at the age of 2 months to 17 years. (2) 22 patients (79%) were infant onset cases with psychomotor retardation, dystonia, seizures, athetosis, recurrent vomiting, drowsiness or feeding difficulty. Only two of the 22 patients with infant onset got normal intelligence and movement after treatment. Twenty of them were improved slowly with delayed development, dystonia and other neurological problems. Three patients (11%) had late onset. They had motor regression, headache and seizure at the age of 8, 9 and 17 years, respectively. Rapid improvement was observed after treatment. (3) Cranial MRI has been checked in 23 patients; 22 of them showed characteristic widening of the Sylvian fissure, abnormalities of the basal ganglia, leukoencephalopathy and brain atrophy. Thirty-five mutations in GCDH gene of the patients were identified; c.148T>C (p.W50R) was the most common mutation with the frequency of 7.7%; 6 mutations (c.628A>G, c.700C>T, c.731G>T, c.963G>C, c.1031C>T and c.1109T>C) were novel.

CONCLUSIONGlutaric aciduria type 1 usually induced neurological deterioration resulting in severe psychomotor retardation and dystonia. Most of our patients were clinically diagnosed. Patients with early onset usually remained having neurological damage. Phenotype and genotype correlation has not been found in the patients. Neonatal screening for organic acidurias should be expanded in China.

Age of Onset ; Amino Acid Metabolism, Inborn Errors ; diagnosis ; genetics ; metabolism ; Brain Diseases, Metabolic ; diagnosis ; genetics ; metabolism ; DNA Mutational Analysis ; Follow-Up Studies ; Gas Chromatography-Mass Spectrometry ; Glutarates ; urine ; Glutaryl-CoA Dehydrogenase ; deficiency ; genetics ; metabolism ; Humans ; Infant, Newborn ; Intellectual Disability ; etiology ; pathology ; Magnetic Resonance Imaging ; Movement Disorders ; etiology ; pathology ; Mutation ; Neonatal Screening ; methods ; Retrospective Studies