Association of Meteorological Factors with Labial Adhesions in Children: A 7-year Retrospective Analysis with 9,467 Cases

Labial adhesions (LA)(also called labial agglutination) are defined as partial or complete agglutination of labia minora. The condition commonly occurs in girls during childhood with an estimated prevalence of 0.6%–5%and a peak incidence in the age-group of 13–24 months[1]. Over half of all patients present with symptoms related to urinary outlet obstruction[2].

Anti-nuclear matrix protein 2+ juvenile dermatomyositis with severe skin ulcer and infection: A case report and literature review

BACKGROUND Juvenile dermatomyositis(JDM)is an idiopathic inflammatory myopathy that occurs in childhood.It is characterized by muscle weakness and a characteristic rash.Previous literature reports have rarely described JDM with severe skin ulcers and infections.CASE SUMMARY Herein,we describe a case of a 2-year-old female patient who suffered from JDM,whose myositis-specific autoantibodies were positive for anti-nuclear matrix protein 2 antibody,with progressively worsening skin ulcers and severe infections.The patient was treated with glucocorticoids and various immunosuppressants.Nevertheless,further progression of the disease and the combination of primary disease and severe infection in the later period were fatal.CONCLUSION In children,anti-nuclear matrix protein 2+JDM combined with skin ulcers often indicates severe disease.In such cases,personalized treatment for the primary disease and infection prevention and control are essential.

Perspectives of genetic management strategy for inherited cardiovascular diseases in China

Inherited cardiovascular diseases(CVDs)threaten human health and pose an enormous economic burden worldwide.Genetic alteration is a major risk factor for many CVDs.These disorders are usually controlled by a pair of alleles,affecting offspring according to the Mendelian principle,regardless of isolated primary damage or secondary injury from other syndromes or deficiency.To date,there are hundreds of inherited CVDs.With advances in nextgeneration sequencing(NGS)technologies,rapid and accurate molecular diagnosis of patients with inherited CVDs is clinically practical.Besides,great improvements have been made in recent years,and targeted therapy and assist devices have been used in clinical practice.Yet there is still no totally efficient strategy for dealing with inherited CVDs.Accordingly.

Primary Immune Deficiencies e A rapidly emerging area of basic and clinical research

In this special issue of Genes&Diseases,Primary Immune Deficiencies(PIDs)are the main focus.This is an exciting and a rapidly emerging field of basic and clinical immunology wherein upwards of 400 clinical conditions,with approximately 350 defined mutations,are now recognized.Contrary to common perception,PIDs as a group are not uncommon.Epidemiologic studies show that population prevalence of PIDs is approximately 1:2000.Statistical extrapolations of this figure would suggest that in a large country like China or India,approximately 1 million individuals would be expected to have a PID.However,at present because of lack of awareness of these conditions amongst both the laity as well as medical professionals,majority of these patients remain undiagnosed and untreated in many developing countries.This is clearly unfortunate.

Continuous positive airway pressure in children with severe pneumonia: a meta-analysis

Pneumonia is the leading cause of death among children aged 1-59 months worldwide[1].WHO recommends providing low flow oxygen by nasal cannula in pediatric patients with oxygen saturation<90%[2].With the provision of oxygen supplementation,some children still require further respiratory support such as mechanical ventilation due to the failure to maintain oxygen saturation and severe respiratory distress[3,4].However,mechanical ventilation may result in ventilator-induced lung injury[5].As a simple and minimally invasive technique,continuous positive airway pressure(CPAP)has been used in children with severe pneumonia[6,7],but its effect and safety are uncertain.Therefore,we performed a meta-analysis that compared CPAP with standard therapy or low-flow oxygen to figure out the effects and safety of CPAP.

PGC-1α promotes mitochondrial respiration and biogenesis during the differentiation of hiPSCs into cardiomyocytes

Although it is widely accepted that human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)are readily available,robustly reproducible,and physiologically appropriate human cells for clinical applications and research in the cardiovascular field,hiPSC-CMs cultured in vitro retain an immature metabolic phenotype that limits their application,and little is known about the underlying molecular mechanism controlling mitochondrial metabolic maturation during human induced pluripotent stem cells(hiPSCs)differentiation into cardiomyocytes.In this study,we found that peroxisome proliferator-activated receptor g coactivator-1α(PGC-1α)played an important role in inducing mitochondrial biogenesis and establishing oxidative phosphorylation(OXPHOS)during the cardiac differentiation of hiPSCs.Knocking down PGC-1α by siRNA impaired mitochondrial respiration,while upregulating PGC-1α by ZLN005 promoted mitochondrial biosynthesis and function by regulating the expression of downstream genes involved in mitochondrial dynamics and oxidative metabolism in hiPSCCMs.Furthermore,we found that estrogen-related receptor a(ERRa)was required for the induction of PGC-1α stimulatory effects in hiPSC-CMs.These findings provide key insights into the molecular control of mitochondrial metabolism during cardiac differentiation and may be used to generate more metabolically mature cardiomyocytes for application.

Novel biallelic TRNT1 mutations lead to atypical SIFD and multiple immune defects

Mutations in the gene encoding transfer RNA(tRNA)nucleotidyltransferase,CCAadding 1(TRNT1),an enzyme essential for the synthesis of the 30-terminal CCA sequence in tRNA molecules,are associated with a rare syndrome of congenital sideroblastic anemia,B cell immunodeficiency,periodic fevers,and developmental delay(SIFD).Clinical manifestations and immunological phenotypes were assessed in a Chinese patient with novel compound heterozygous mutations in TRNT1.The patient required multiple hospitalizations starting at the age of 2 years for recurrent fevers without an infective cause.During the febrile episode,the patient was found to have microcytic hypochromic anemia,B cell lymphopenia,and hypogammaglobulinemia.Targeted gene sequencing identified novel compound heterozygous mutations in the TRNT1 gene(c.525delT,p.Leu176X;c.938T>C,p.Leu313Ser).Immunophenotyping revealed increased CD8^+T cells,CD4^+ terminally differentiated effector memory helper T lymphocytes(CD4 TEMRA),and CD4^+ effector memory lymphocytes(CD4 EM).Analysis of CD4^+T subsets identified decreased T follicular helper cells(Tfh)with a biased phenotype to Th2-like cells.The patient also showed a lower percentage of switched memory B(smB)cells.Additionally,defects in the cytotoxicity of the patient’s NK andγτT cells were shown by CD107alpha expression.In conclusion,TRNT1 mutations may lead to multiple immune abnormality especially humoral and cytotoxicity defects,which indicate that SIFD is not only suffered‘Predominantly antibody deficiencies’in IUIS classification system,and further studies are needed to understand the pathogenesis of immunodeficiency in these patients.

Inhibition of cystathionine β-synthase promotes apoptosis and reduces cell proliferation in chronic myeloid leukemia

Increased endogenous hydrogen sulfide(H_(2)S)level by cystathionine β-synthase(CBS)has been shown to closely relate tumorigenesis.H_(2)S promotes angiogenesis,stimulates bioenergy metabolism and inhibits selective phosphatases.However,the role of CBS and H_(2)S in chronic myeloid leukemia(CML)remains elusive.In this study,we found that CBS and H_(2)S levels were increased in the bone marrow mononuclear cells of pediatric CML patients,as well as in the CML-derived K562 cells and CBS expression levels were correlated with different disease phases.Inhibition of CBS reduced the proliferation of the CML primary bone marrow mononuclear cells and induced growth inhibition,apoptosis,cell cycle arrest,and migration suppression in K562 cells and tumor xenografts.The knockdown of CBS expression by shRNA and inhibiting CBS activity by AOAA decreased the endogenous H_(2)S levels,promoted mitochondrial-related apoptosis and inhibited the NF-xB-mediated gene expression.Our study suggests that inhibition of CBS induces cell apoptosis,as well as limits cell proliferation and migration,a potential target for the treatment of chronic myeloid leukemia.

Corrigendum to “Novel biallelic TRNT1 mutations lead to atypical SIFD and multiple immune defects” [Genes Dis 7 (1) (2020) 128-137]

We regret that an error was made in“Novel biallelic TRNT1 mutations lead to atypical SIFD and multiple immune defects”(Volume 7,Issue 1,March 2020,Pages 128e137).In the original manuscript,the grant number of the Natural Science Foundation of China was incorrectly written with the project number.The correct grant number is 81601753.We apologize for the error and for any inconvenience that may cause to the readers and the editors of this journal.

Phenotypic characterization of patients with activated PI3Kδ syndrome 1 presenting with features of systemic lupus erythematosus

Activated phosphoinositide 3-kinase d syndrome 1(APDS1)is a primary immunode-ficiency disease caused by gain-of-function mutations in PIK3CD.Clinical features of autoimmune disease have been reported in patients with APDS1.In this study,we reported three patients with APDS1 presenting with systemic lupus erythematosus(SLE)phenotype.The clinical manifestations included recurrent respiratory tract infection,lymphoproliferation,Coombs-positive hemolytic anemia,decreased complement fractions,positive antinuclear antibodies,renal complications related to SLE associated diseases,which met the clinical spectrum of APDS1 and the classification criteria of SLE.The immunological phenotype included an inversion in the CD4:CD8 ratio,an increase in both non-circulating Tfh CD4^(+)memory T and circulating Tfh populations,a low level of recent thymic emigrant T cells,overexpression of CD57 on T cells,and a decrease in B cells with fewer antibody class switch recombination.These phenotypes detected in patients with APDS1 presenting with SLE were resemble that in patients with APDS1 presenting without SLE.Meanwhile,we described the effect of glucocorticoids and rapamycin therapy on patients with APDS1.The phosphorylation of S6 at Ser235/236 was inhibited in patients with APDS1 who underwent glucocorticoids therapy,including two who presented with SLE phenotype.The phosphorylation of AKT at Ser473 and phosphorylation of S6 at Ser235/236 were inhibited in other patients with APDS1 who underwent rapamycin therapy.Here,we showed the coexistence of immunodeficiency and SLE phenotype in APDS1,and the inhibition of rapamycin in activated Akt-mTOR signaling pathway.

Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1a expression participates in neural restoration in hypoxic-ischemic brain damagerats

The transplantation of human umbilical cord mesenchymal stem cells(hUC-MSCs)can promote hypoxic-ischemic brain damage(HIBD)nerve repair,but finding suitable seed cells to optimize transplantation and improve treatment efficiency is an urgent problem to be solved.In this study,we induced hUC-MSCs into dedifferentiated hUC-MSCs(De-hUC-MSCs),and the morphology,stem cell surface markers,proliferation and tri-directional differentiation ability of the De-hUC-MSCs and hUC-MSCs were detected.A whole-gene chip was utilized for genome cluster,gene ontology and KEGG pathway analyses of differentially expressed genes.De-hUC-MSCs were transplanted into HIBD rats,and behavioral experiments and immunofluorescence assays were used to assess the therapeutic effect.A lentivirus vector for human stromal cell-derived factor-1(hSDF-1a)was constructed,and the role of hSDF-1a in the neuroprotective effect and mechanism of De-hUC-MSCs was verified.De-hUC-MSCs displayed similar cell morphology,stem cell surface marker expression,cell proliferation and even three-dimensional differentiation ability as hUC-MSCs but exhibited greater treatment potential in vivo.The reprogramming mechanism of hSDF-1a participated in the dedifferentiation process.By successfully constructing a stable hSDF-1a cell line,we found that De-hUC-MSCs might participate in nerve repair through the hSDF-1a/CXCR4/PI3K/Akt pathway.De-hUC-MSCs reprogramming of endogenous hSDF-1a expression may mediate the hSDF-1a/CXCR4/PI3K/Akt pathway involved in nerve repair in HIBD rats.