[Holocarboxylase synthetase deficiency induced by HLCS gene mutations: a rare disease study]. / ç½•è§ç— ç ”ç©¶ï¼šHLCSåŸºå› çªå˜è‡´å ¨ç¾§åŒ–é ¶åˆæˆé ¶ç¼ºä¹ç—‡.

A boy, aged 16 months, attended the hospital due to head and facial erythema for 15 months and vulva erythema for 10 months with aggravation for 5 days. The boy developed perioral and periocular erythema in the neonatal period and had erythema and papules with desquamation and erosion in the neck, armpit, and trigone of vulva in infancy. Blood gas analysis showed metabolic acidosis; the analysis of amino acid and acylcarnitine profiles for inherited metabolic diseases and the analysis of organic acid in urine suggested multiple carboxylase deficiency; genetic testing showed a homozygous mutation of c.1522C>T(p.R508W) in the HLCS gene. Finally the boy was diagnosed with holocarboxylase synthetase deficiency and achieved a good clinical outcome after oral biotin treatment. This article analyzes the clinical data of a child with holocarboxylase synthetase deficiency and summarizes the etiology, diagnosis, and treatment of this child, so as to provide ideas for clinicians to diagnose this rare disease.

[Recurrent systemic sporadic rash for 10 years in a girl aged 11 years]. / 11å²å¥³å­©åå¤å ¨èº«æ•£åœ¨çš®ç–¹10å¹´.

A girl, aged 11 years, was admitted due to recurrent rash on the whole body and mucosa for 10 years, and typical rash was erythema at the perioral region, hand-foot joints, vulva, and perianal region, with blisters, erosions, and ulcers on the erythema. The girl was improved after zinc supplementation. Her younger brother had similar rash and medical history. The histopathological examination showed epidermal parakeratosis with mild hyperkeratosis, severe spongiform edema of the stratum corneum, significant proliferation of acanthocytes, and vacuolation of keratinocytes. The genetic testing revealed that both the girl and her younger brother had a homozygous mutation of c.1456(exon9)delG in the SLC39A4 gene, and thus the girl was diagnosed with acrodermatitis enteropathica. It is concluded that for children with recurrent rash on the limbs and at the perioral region, genetic testing should be performed as early as possible to make a confirmed diagnosis, and a sufficient dose of zinc supplementation should be given, while the levels of trace elements such as blood zinc should be regularly monitored.

[Recurrent vulvar rashes in a girl aged 22 months for more than half a year].

A girl, aged 22 months, attended the hospital due to recurrent vulvar rashes for more than half a year. Skin biopsy showed Langerhans cell histiocytosis, and evaluation of systemic conditions showed no systemic involvement. Therefore, the girl was diagnosed with Langerhans cell histiocytosis (skin type). In conclusion, for rashes on the vulva alone, if there are no specific clinical manifestations, the possibility of Langerhans cell histiocytosis should be considered after molluscum contagiosum, sexually transmitted diseases, and Fordyce disease are excluded.

[Recurrent skin blisters for more than 7 months in a girl aged 15 months].

A girl, aged 15 months, attended the hospital due to recurrent skin erythema, blisters, and desquamation for more than 7 months. Giemsa staining and immunohistochemical staining showed mast cell infiltration and degranulation. Hematoxylin staining showed spinous layer edema and blister formation under the epidermis, with a large amount of serous fluid and a small number of inflammatory cells in the blister. Marked edema was observed in the dermis, with diffused mononuclear cell infiltration. The girl was diagnosed with mastocytosis. Mastocytosis should be considered for children with recurrent skin erythema and blisters.

[Unexpected cutaneous purpura in an infant].

A two-month-old boy visited the hospital due to unexpected cutaneous purpura and thrombocytopenia for 2 days. The physical examination revealed a purple mass on the back. The soft tissue color Doppler ultrasound showed rich blood signals in the tissue, and the results of bone marrow puncture indicated an increased number of megakaryocytes. After the treatment with hormone and gamma globulin, the platelet count rapidly increased and maintained at a normal level. Meanwhile, the boy was given oral administration of propranolol. He was followed up for 4 months and the volume of the mass on the back was reduced significantly. He had a definite diagnosis of hemangioma and immune thrombocytopenia. As for the patients with hemangioma complicated by thrombocytopenia, knowledge of Kasabach-Merritt syndrome should be enhanced and there should be a clarification of the association between thrombocytopenia and hemangioma. There should also be an alertness for thrombocytopenia of other causes.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

Clinical characteristics of moderate or severe COVID-19 infection in patients with rheumatic diseases and analysis of risk factors leading to severe disease.

OBJECTIVE: To explore the clinical characteristics of rheumatic disease (RD) patients who suffered from moderate or severe coronavirus disease 2019 (COVID-19) infection and to evaluate risk factors of COVID-19 infection in RD patients. METHODS: A retrospective analysis was conducted on 148 moderate or severe COVID-19 patients admitted to the First People's Hospital of Suqian Affiliated to Nanjing Medical University, including 74 RD patients and 74 non-RD patients. Clinical data were collected including clinical characteristics and laboratory tests. RESULTS: The RD group showed a higher proportion of females with a higher incidence of interstitial lung disease and kidney disease than the non-RD group. Also, the incidence of fatigue, olfactory dysfunction and musculoskeletal pain was higher in the RD group, but the incidence of cough, wheezing, and fever was lower compared with non-RD patients. The hospitalized course of the RD group (12.7 days ± 6.55) was significantly longer than that in the non-RD group (8.07 days ± 3.40). Also, patients in the RD group had higher levels of erythrocyte sedimentation rate, interleukin (IL)-2, and IL-4 than the non-RD group. The logistic regression analysis showed that dizziness and headache, C-reactive protein (CRP) > 8 mg/L and lactate dehydrogenase (LDH) > 248 µ/L were independent risk factors for severe COVID-19 infections of RD patients. CONCLUSION: RD patients who suffered from moderate or severe COVID-19 infections have a higher risk of comorbidities, higher levels of inflammation, and longer hospitalized course. Dizziness and headache, CRP > 8 mg/L and LDH > 248 µ/L are risk factors for severe COVID-19 infections in RD patients.

Cu-Modified La2Si2O7/TiO2 composite materials: preparation, characterization and photothermal properties.

Cu-Modified La2Si2O7/TiO2 composite materials were prepared by the molten salt method and a solid-phase reduction strategy. Due to the surface plasmon resonance (SPR) of copper, the optical response from the UV to the visible region and near-infrared is increased. In the meantime, it enhances the absorption of visible light by the titanium dioxide and acts as a plasma catalyst. The combination enhances the photothermal properties of the composite. The particle size of Cu/La2Si2O7/TiO2 is in the range of 100 to 230 nm. Results show that the composite has a good photothermal effect. The 1 mg ml-1 solution can be warmed up to 63.1 °C at 0.5 W cm-2 laser power density with a maximum temperature difference of 45 °C. It has potential applications in solar energy conversion, photothermal catalysis, etc.

Epidemiology of Takayasu arteritis in Shanghai: A hospital-based study and systematic review.

BACKGROUND: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. METHODS: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. RESULTS: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. CONCLUSIONS: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

[Investigation of allergens in 3,504 children with allergic diseases].

OBJECTIVE: To investigate the allergens of various allergic diseases in children. METHODS: Serum levels of Fx5E, Phadiatop and specific IgE were measured by the UniCAP100 System in 3 504 children with allergic diseases. RESULTS: The positive rate of aeroallergens was obviously higher than that of food allergens in children with allergic rhinitis, allergic conjunctivitis, asthma and papular urticaria. In contrast, the positive rate of food allergens was obviously higher than that of aeroallergens in children with Henoch-Schonlein purpura and digestive diseases. The serum specific IgE level of aeroallergens was higher than that of food allergens. The dust and mite specific IgE levels reached to grade 6, while the food allergen specific IgE levels were lower than grade 3. CONCLUSIONS: Aaeroallergens or food allergens vary remarkably in different allergic diseases in children. The level of specific IgE of aeroallergens is higher than that of food allergens.

[Expression of blood Toll-like receptors and cytokines in children with recurrent herpes simplex].

OBJECTIVE: This study examined the expression of Toll-like receptors (TLR) in peripheral blood mononuclear cells (PBMC) and serum levels of IL-6, IL-10 and TNF-alpha in children with recurrent herpes simplex, in order to investigate the role of TLR2 and TLR9 in recurrent herpes simplex. METHODS: The expression of TLR2 and TLR9 in PBMC was examined by flow cytometer, and serum levels of IL-6, IL-10 and TNF-alpha were detected using ELISA in 22 children with recurrent herpes simplex and in 13 age-matched healthy volunteers. RESULTS: The expression of both TLR2 and TLR9 obviously increased in children with recurrent herpes simplex compared with that in healthy controls (p<0.01). Serum levels of IL-6 and IL-10 increased, while serum TNF-alpha levels decreased significantly in children with recurrent herpes simplex compared with those in healthy controls (p<0.01). There were positive correlations between TLR2 and TLR9 expression and serum IL-6 and IL-10 levels in children with recurrent herpes simplex (p<0.01). CONCLUSIONS: TLR2 and TLR9 in PBMC may participate in the recognition of herpes simplex virus and activate the signal pathway of TLR in children with recurrent herpes simplex. The production and release of IL-6 and IL-10 might be mediated by TLR2 and TLR9.

[Detection of serum specific IgE in 437 children with allergic disease].

OBJECTIVE: To investigate the distribution of allergens in children with allergic disease in Changsha. METHODS: Total IgE and specific IgE against some allergens were examined by the AllergyScreen system in the sera of 437 children from Changsha with allergic disease. RESULTS: The positive rates of total IgE and special IgE were 68.9% and 69.1% respectively. Dermatophagoides farina, beef, mutton, milk and fur of cats and dogs were found as common allergens. The IgE positive rate against dermatophagoides farina was the highest in children with allergic rhinitis (86.0%), followed by in those with atopic dermatitis (41.2%), eczema (27.6%) and urticaria (20.0%). Serum IgE was positive against the fur of cats and dogs in 23.5% of children with atopic dermatitis and in 18.1% of children with eczema. The IgE positive rate was lower in children with urticaria and allergic rhinitis (10.0% and 8.7% respectively). IgE positive rates against milk, beef and mutton were high in the above four allergic diseases (range: 14.0%-24.0%), but no significant differences were observed for the IgE positive rate among the four allergic diseases. The IgE positive rate to inhalant allergens in children at ages of less than 3 years was markedly higher than that in children at ages of more than 3 years (p<0.01). CONCLUSIONS: Allergic diseases are mainly mediated by allergens. Allergens, especially dermatophagoides farina, fur of cats and dogs, beef, mutton and milk, play an important role in childhood allergic diseases in Changsha.

Systemic Alanine Glyoxylate Aminotransferase mRNA Improves Glyoxylate Metabolism in a Mouse Model of Primary Hyperoxaluria Type 1.

Primary Hyperoxaluria Type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism. Loss of alanine glyoxylate aminotransferase (AGT) function to convert intermediate metabolite glyoxylate to glycine causes the accumulation and reduction of glyoxylate to glycolate, which eventually is oxidized to oxalate. Excess oxalate in PH1 patients leads to the formation and deposition of calcium oxalate crystals in the kidney and urinary tract. Oxalate crystal deposition causes a decline in renal function, systemic oxalosis, and eventually end-stage renal disease and premature death. mRNA-based therapies are a new class of drugs that work by replacing the missing enzyme. mRNA encoding AGT has the potential to restore normal glyoxylate to glycine metabolism, thus preventing the buildup of calcium oxalate in various organs. Panels of codon-optimized AGT mRNA constructs were screened in vitro and in wild-type mice for the production of a functional AGT enzyme. Two human constructs, wild-type and engineered AGT (RHEAM), were tested in Agxt-/- mice. Repeat dosing in Agxt-/- mice resulted in a 40% reduction in urinary oxalate, suggesting therapeutic benefit. These studies suggest that mRNA encoding AGT led to increased expression and activity of the AGT enzyme in liver that translated into decrease in urinary oxalate levels. Taken together, our data indicate that AGT mRNA may have the potential to be developed into a therapeutic for PH1.

Quantitative Systems Pharmacology Model of hUGT1A1-modRNA Encoding for the UGT1A1 Enzyme to Treat Crigler-Najjar Syndrome Type 1.

Crigler-Najjar syndrome type 1 (CN1) is an autosomal recessive disease caused by a marked decrease in uridine-diphosphate-glucuronosyltransferase (UGT1A1) enzyme activity. Delivery of hUGT1A1-modRNA (a modified messenger RNA encoding for UGT1A1) as a lipid nanoparticle is anticipated to restore hepatic expression of UGT1A1, allowing normal glucuronidation and clearance of bilirubin in patients. To support translation from preclinical to clinical studies, and first-in-human studies, a quantitative systems pharmacology (QSP) model was developed. The QSP model was calibrated to plasma and liver mRNA, and total serum bilirubin in Gunn rats, an animal model of CN1. This QSP model adequately captured the observed plasma and liver biomarker behavior across a range of doses and dose regimens in Gunn rats. First-in-human dose projections made using the translated model indicated that 0.5 mg/kg Q4W dose should provide a clinically meaningful and sustained reduction of >5 mg/dL in total bilirubin levels.

[Twenty Y-STR locus multiplex amplification and genetic polymorphism analysis in Han population in Chaoshan area].

OBJECTIVE: To study genetic polymorphisms of 20 Y-chromosomal short tandem repeats (STR) in Chaoshan Han population, and to evaluate their value in forensic science. METHODS: Twenty Y-specific STR loci (DYS434, Y-GATA-A10, Y-GATA-H4, DYS438, DYS439, DYS443, DYS444, DYS446, DYS447, DYS448, DYS456, DYS458, DYS460, DYS520, DYS531, DYS557, DYS622, DYS630, DYS635 and DYS709) were amplified by using three fluorescence-labeled multiplex PCR systems and were analyzed by ABI310 genetic analyzer. One hundred and fifty-eight unrelated male individuals of Han population in Chaoshan area were investigated to determine the distribution of allele frequencies and haplotype. RESULTS: The Y-STR multiplexes developed had followed the published nomenclature and ISFG guidelines for STR analysis. Gene diversity ranged from 0.2506 at DYS434 to 0.8034 at DYS447. A total of 157 different haplotypes were observed, and among these, 156 were unique, while 1 was found for two times. The haplotype diversity value calculated from all 20 loci combined was 0.999998. None of Y-STR allele mutation was observed in the 30 father/ son pairs confirmed by autosomal STR analysis. CONCLUSION: The results indicate that the 20 Y-STR loci are highly polymorphic and fathership genealogy inheritance are stable. The three fluorescence-labeled multiplex amplification systems that we constructed are suitable for forensic individual identification and paternity testing in Chaoshan area.

[Application of MiniFiler kit in forensic DNA testing of low copy number template].

OBJECTIVE: To detect low copy number of DNA samples by using a newly launched commercial miniSTR detection kit (MiniFiler) in forensic practice. METHODS: Low concentration and/or challenged forensic DNA samples were analyzed according to protocols provided by the manufacturer (Applied Biosystems, Foster City, USA). RESULTS: DNA samples as low as 10 pg could be amplified by MiniFiler kit, and the optimal DNA quantity was 40 pg or above. CONCLUSION: MiniFiler kit can be used for analysis of low copy number STR.

Novel phenotypes of NF1 patients from unrelated Chinese families with tibial pseudarthrosis and anemia.

Neurofibromatosis type 1 (NF1) is an autosomal dominant, multi-system, neurocutaneous disorder, manifested with neurofibromas and Cafe´-au-lait spots. Germline mutations in NF1 gene are associated with Neurofibromatosis type 1. NF1 gene encodes neurofibromin, a RAS-specific GTPase activating protein. In our study, we present a clinical molecular study of four Chinese probands with NF1 from four unrelated families, showing extreme phenotypic variation with rare phenotype. In family 1, the proband is a 16 months old girl with multiple café-au-lait spots throughout her whole body. In family 2, the proband is a 6 months old girl with several café-au-lait spots mostly in her trunk and in lower limbs. In family 3, the proband is a 4 months old boy with several café-au-lait spots, tibial pseudarthrosis, and chronic iron deficiency anemia. In family 4, the proband is a 14 years old boy with multiple café-au-lait spots of variable sizes. Targeted exome capture based next generation sequencing and Sanger sequencing identified a novel mutation and three previously reported mutations in these four probands. These four mutations in NF1 gene were causing disease phenotypes in these four probands and was absent in unaffected family members and in healthy controls. According to the variant interpretation guideline of American College of Medical Genetics and Genomics (ACMG), these four mutations, are classified as "likely pathogenic". Our result expands the mutational spectrum of the NF1 gene associated with neurofibromatosis type1.

Effect of mesenchymal stem cells on Sjögren-like mice and the microRNA expression profiles of splenic CD4+ T cells.

Mesenchymal stem cells (MSCs) serve immuno-regulatory functions and offer a promising novel treatment for certain autoimmune diseases. The present study investigated the therapeutic effect of mice bone marrow (BM)-MSCs on mice with relatively late stage of Sjögren-like disease and the impact of BM-MSCs on the microRNA (miRNA) expression profiles of splenic CD4+ T cells. Female NOD/Ltj mice were randomized into two groups: The disease group (n=8) and the MSC-treated group (n=8). Female ICR mice served as the healthy control group (n=8). The MSC-treated group received an injection of MSCs when they were 26 weeks old. Water intake, blood glucose and salivary flow rate were measured and submandibular glands were resected and stained with hematoxylin and eosin to calculate the focus score. The concentrations of interleukin (IL)-2, IL-6, hepatocyte growth factor, interferon γ, IL-10, prostaglandin E2, transforming growth factor ß1 and tumor necrosis factor-α in serum were measured using ELISA. The expression of miRNAs in splenic CD4+ T cells were measured using deep sequencing. The results demonstrated that treatment with BM-MSCs prevented a decline in the salivary flow rate and lymphocyte infiltration in the salivary glands of NOD mice, indicating that MSC-treatment had a therapeutic effect on NOD mice with relatively late stage of Sjögren-like disease. ELISA and deep sequencing results showed that the three groups of mice had different serum concentrations of cytokines/growth factors and different miRNA expression profiles of splenic CD4+ T cells. This implies that the alteration in serum levels of cytokines/growth factors and miRNA expression profiles of splenic CD4+ T cells may explain the therapeutic effect MSCs have on Sjögren's syndrome.