Objective:To analyze the gene mutation type and clinical phenotype of patients with PRRT2 mutation, and explore their relations with prognosis. Methods:A total of 18 patients with PRRT2 gene mutation (1 patient with novel mutation in PRRT2 gene, and 17 probands in 17 families with PRRT2 gene mutation) were enrolled in Department of Neurology, First Affiliated Hospital of Air Force Medical University from January 2018 to July 2023. Serum of the patients was collected for whole exon sequencing, and mutation sites and types of PRRT2 gene were analyzed. SWISS-MODEL website was used to predict the changes in protein structure caused by PRRT2 gene mutation. The relations of gene mutation type and clinical phenotype with prognosis of these patients were analyzed. Results:(1) All 18 patients with PRRT2 gene mutation were heterozygous mutation, including 12 frameshift mutations, 5 missense mutations, and 1 integer mutation. The clinical phenotype included benign familial infantile epilepsy (BFIE) in 5 patients, epilepsy in 6 patients, exercise-induced paroxysmal kinesigenic dyskinesia (PKD) in 5 patients, and infantile convulsion and choreoathetosis (ICCA) in 2 patients. A total of 8 mutation sites were found in 18 patients with PRRT2 gene mutation, of which 3 mutation sites have been reported, and 5 mutation sites have not been reported, including c.647(exon2)C>A, c.647(exon2)C>G, c.170(exon2)delC, c.981(exon3)C>G, and lossl(EXON: 2)(all). (2) Eighteen patients mainly accepted oxcarbazepine, levetiracetam, and sodium valproate in combination or monotherapy. Among them, 5 BFIE patients, 2 ICCA patients and 3 epilepsy patients were seizure-free after treatment. PKD patients did not respond well to oxcarbazepine. (3) Three frameshift mutations (mutation sites: c.649 [exon2]_c.650 [exon2] insC, c.640 [exon2]_c.641 [exon2] insC, and c.170 [exon2] delC) led to premature termination of protein translation, resulting in significant changes in protein structure. Four missense mutations (mutation sites: c.640[exo2]G>C, c.647[exon2]C>A, c.647[exon2]C>G, and c.981[exon3]C>G) had little effect on protein structure changes. No relation was found between changes of protein structure caused by different mutation types and prognosis. Conclusion:PRRT2 gene mutation patients with clinical phenotypes of BFIE and ICCA have good prognosis, but the mutation type is not related with the prognosis of patients.

Objective To explore the related factors affecting the sensitivity of neoadjuvant immuno-therapy combined with chemotherapy for treating esophageal squamous cell carcinoma(ESCC).Methods The clinical data of 51 cases of ESCC were retrospectively analyzed.The patients were divided into the neoad-juvant immunotherapy combined with chemotherapy sensitivity group(n=29)and resistance group(n=22)according to the treatment effects.The statistical methods were employed to analyze the factors affecting the sensitivity of neoadjuvant immunotherapy combined with chemotherapy for treating ESCC.Results The uni-variate analysis results showed that the lesion depth detected by CT after treatment had statistical difference between the sensitivity group and resistance group(P＜0.001).The lesion depth also had statistical difference before and after treatment(P=0.002).The endoscopic evaluation showed that the proportion of the patients with pathological remission in the sensitivity group was higher than that in the resistance group with statisti-cal difference(P＜0.001).The multivariate analysis results showed that degree of pathological remission(P=0.042,95％CI:1.096-161.519)and pathological lymph node metastasis(P=0.025,95％CI:0.003-0.670)evaluated by endoscopy were the independent influencing factors of the sensitivity to neoadjuvant im-munotherapy combined with chemotherapy.Meanwhile,the patients with tumor infiltration depth difference≥0.750 cm measured by CT were more sensitive to the immunotherapy combined with chemotherapy(AUC=0.750,sensitivity 41.4％,specificity 55.0％,P=0.002,95％CI:0.618-0.882).Conclusion Preop-erative chest CT calculation of lesion depth and endoscopic assessment of pathological remission degree could predict the sensitivity of ESCC patients to neoadjuvant immunotherapy combined with chemotherapy,which provides reference for formulating the treatment regimen,however,it is necessary to enlarge the sample size and further study the various influencing factors.

OBJECTIVE: To explore the clinical feature and genetic etiology of a patient with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) due to variant of CHD7 gene. METHODS: A patient who had presented at Anhui Provincial Children's Hospital in October 2022 was selected as the study subject. Clinical data of the patient was collected. The patient and his parents were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The patient had featured delayed development of secondary sexual characteristics but normal olfactory function. Genetic testing revealed that he has harbored a c.3052C>T (p.Pro1018Ser) missense variant of the CHD7 gene, for which both of his parents were of the wild type. The variant has not been recorded in the PubMed and HGMD databases. Analysis of amino acid sequences suggested that the variant site is highly conserved, and the variant may affect the stability of protein structure. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.3032C>T variant was classified as a likely pathogenic (PS2+PM2_Supporting+PP2+PP3+PP4). CONCLUSION The delayed development of secondary sexual characteristics of the patient may be attributed to the c.3052C>T (p.Pro1018Ser) variant of the CHD7 gene. Above finding has expanded the variation spectrum of the CHD7 gene.
Child ; Humans ; Male ; Amino Acid Sequence ; Computational Biology ; DNA Helicases/genetics* ; DNA-Binding Proteins/genetics* ; Genetic Testing ; Genomics ; Hypogonadism/genetics* ; Mutation

Objective:To investigate the role of miR-146a in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA) and its clinical significance.Methods:This article is a prospective clinical cohort study.Twenty-six patients with sJIA (14 cases of initial active group and 12 cases of stable group), 15 patients with multijoint juvenile idiopathic arthritis (JIA) and 15 patients with oligojoint JIA diagnosed in the Department of Rheumatology and Immunology of Anhui Provincial Children′s Hospital from June 2018 to December 2020 were enrolled.Twenty healthy controls from the out-patient clinic were also recruited.The expression level of miR-146a in peripheral blood mononuclear cells (PBMCs) of research objects was detected by real-time fluorescence quantitative polymerase reaction (qPCR), and the serum levels of interleukin (IL) - 6, tumor necrosis factor (TNF) - α and IL-1β in sJIA patients and healthy controls were detected by enzyme-linked immunosorbent assay.The expression levels of miR-146a in PBMCs and cytokines among different groups were compared by analysis of variance. Pearson correlation analysis was used to analyze the correlation of the relative expression level of miR-146a in PBMCs with clinical inflammatory indexes and serum cytokines in sJIA patients. Results:(1) The expression level of miR-146a in PBMCs of early sJIA patients was significantly higher than that in the multijoint JIA group and oligojoint JIA group (8.77±3.15 vs.4.40±1.59, 2.55±1.15, t=6.27, 14.23; all P<0.05). The expression level of miR-146a in PBMCs of sJIA active patients was significantly higher than that in sJIA stable patients (8.77±3.15 vs.3.63±1.37, t=10.27, P<0.05). There was no significant difference in the expression level of miR-146a between the sJIA stable group and healthy control group ( P>0.05). (2) The expression levels of IL-1β, IL-6 and TNF-α were significantly higher in sJIA active patients group than those in sJIA stable group[(58.56±17.47) ng/L vs.(26.32±10.54) ng/L, (73.72±11.16) ng/L vs.(23.20±9.12) ng/L, (70.93±19.97) ng/L vs.(24.25±9.49) ng/L, all P<0.05]. There was no significant difference in the expression levels of IL-1β, IL-6 and TNF-α between the sJIA stable group and healthy control group(all P>0.05). (3)The expression of miR-146a in PBMCs of sJIA patients was positively correlated with serum ferritin levels, platelets, erythrocyte sedimentation rates, C-reactive proteins, IL-1β, IL-6 and TNF-α( r=0.542, 0.433, 0.329, 0.306, 0.333, 0.342, 0.319, all P<0.05). Conclusions:miR-146a may be involved in the inflammatory process of sJIA disease.miR-146a can well distinguish sJIA from multijoint JIA and oligojoint JIA.TNF-α, IL-1β and IL-6 are involved in sJIA inflammatory responses.

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

OBJECTIVE: To investigate the clinical characteristics and genetic basis for a child with Keppen-Lubinsky syndrome (KPLBS). METHODS: Trio-whole exome sequencing (Trio-WES) was carried out for the proband and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child has featured peculiar facies including large eyes, alar hypoplasia, microretrognathia, premature aging appearance in addition with growth delay and mental retardation. Trio-WES has identified that she has carried a de novo variant of the KCNJ6 gene, namely c.460G>C (p.Gly154Arg). The variant has not been recorded in the database. Prediction of protein structure indicated that the variant may affect the potassium ion selective filtration structure channel in the transmembrane region of KCNJ6 protein, which may result in up regulation of the function of the channel. CONCLUSION The de novo c.460G>C (p.Gly154Arg) variant of the KCNJ6 gene probably underlay the KPLBS in this child. Above finding has enriched the genotypic and phenotype spectrum of this syndrome.
Cataract ; China ; Female ; G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics* ; Humans ; Hypogonadism/congenital* ; Intellectual Disability/genetics* ; Mutation ; Whole Exome Sequencing

Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.
Child ; Child, Preschool ; Consensus ; Dental Caries/prevention & control* ; Dental Caries Susceptibility ; Humans ; Oral Health

Objective:To systematically retrieve, evaluate and summarize the research evidence on the measurement method of adult nasogastric tube indwelling length and provide a basis for clinical nursing practice.Methods:To search for Cochrane Library(CD-SR, DARE), Joanna Briggs(JBI), PubMed (MEDLINE), Web of Science electronic database, China Biomedical Literature Database (CBM), Wanfang Database, China Knowledge Network from the establishment of the database to December 2018. Two researchers independently evaluated the quality of the literature and extracted the data.Results:A total of 9 articles were included in the study. The recommended anatomical landmarks for measuring the length of the inserted gastric tube included XNE, NEX, XJN, Hanson method, GWNUF model, earlobe to xiphoid to navel-nose tip to earlobe NEX 10 cm. The tip of the nasogastric tube and all its lateral hole locations obtained by the Hanson method, the GWNUF model, and the XEN 10 cm method were more likely to be located in the stomach.Conclusion:Although NEX is an external measurement method that is widely used in clinical practice, it has proven to be insufficiently accurate and has considerable risks. Therefore, the method of measuring the length of the nasogastric tube insertion should be carefully selected for teaching or use in practice.

【Objective】 To analyze the blood samples sent by hospitals in Shenzhen to solve ABO cross-match incompatibility during 2011 to 2020, so as to find corresponding solutions to improve the efficacy of blood transfusion. 【Methods】 The clinical data of 1 770 cases of cross-match incompatibility in our laboratory from January 2011 to December 2020 were collected and reviewed. The causes of cross-match incompatibility were analyzed, the types of unexpected antibodies were determined. The overall incidence of antibodies was evaluated by statistical method of classified variables. The safety of blood transfusion was safeguarded by ABO homotype plus cross-matching compatibility. 【Results】 1) The 1 770 samples, presenting cross-matching incompatibility, involved 956 patients. The average number of cross-matching per patient from 2011 to 2015 was 1.32(307/232), which increased from 1.27(103/81) in 2016 to 2.23(286/128) in 2018, and remained stable in 2019 and 2020. 2) Among 956 patients, auto-and/or allo-antibody in plasma were yielded in 90.38%(864/956), including auto-antibody plus alloantibody in 42.26%(404/956), solo auto-antibody in 20.71%(198/956) and solo allo-antibody in 27.41%(262/956). Up to 20 kinds of specific allo-antibodies were detected, belonging to 8 blood groups. Among them, 70.82%(551/778) were Rh blood group, such as anti-E(37.15%)>anti-c(20.95%)>anti-C(5.27%)=anti-e(5.27%)>anti-D(2.19%), followed by MNS [11.40%(112/778)], Kidd [5.66%(44/778)], Leiws [3.21%(25/778)], Duffy [1.80%(14/778)], Diego [1.03%(8/778)], P1 [0.39%(3/778)] and H [0.26%(2/778)]. 3) 86%(37/43) of multiple transfusion recipients, aged below 20 years old, were thalassemia, and 1-4 kinds of allo- and/or auto-antibody were yielded. 【Conclusion】 The cross-matching incompatibility were mainly caused by allo- and/or auto-antibodies, which may be induced by blood transfusion, pregnancy or autoimmune diseases such as autoimmune hemolytic anemia.Those suspicious blood samples in clinical should be sent to blood group reference laboratory for further determination, in order to ensure the safety and efficacy of blood transfusion.

Objective:To explore the influencing factors of 31-day unplanned readmission in obstetrics.Methods:The medical records and relevant clinical data of 29 public hospitals in a province in 2017 were collected to construct a two-level logistic regression model on the influencing factors of 31-day unplanned readmission.Results:In 2017, there were 71 330 obstetric patients discharged from 29 public hospitals, 690 of whom were unplanned readmitted in 31 days, accounting for 0.97%. The type of medical insurance payment, number of previous hospitalization, condition of previous hospitalization, age, history of cesarean section, pregnancy complications and complications during delivery were all the factors influencing the 31-day unplanned readmission of obstetrics.Conclusions:The condition of 31-day unplanned readmission could be influenced by the factors of sociology, previous visit and clinical. These factors should be considered reasonably in the evaluation and management of obstetric quality.