ObjectiveTo explore the clinical features and causative genes of short stature children with unknown etiology， providing evidence for precise clinical diagnosis and treatment. MethodsThe study recruited children with suspected but undiagnosed short stature from the pediatric endocrinology department in our hospital between January 2018 and August 2022. A retrospective analysis was performed on the clinical manifestations， laboratory test and whole exome sequencing （WES） results. Causative genes were classified and analyzed according to different pathogenic mechanisms. ResultsA total of 48 children （30 boys and 18 girls） were enrolled， aged 7.73 ± 3.97 years， with a height standard deviation score （ HtSDS） of -3.63 ± 1.67. Of the patients， 33 （68.8%） suffered from facial anomalies， 31 （64.6%） from skeletal abnormalities， 26 ［54.2%， 61.5% of whom born small for gestational age （SGA）］ from perinatal abnormalities， 24 ［50.0%， 87.5% of whom with growth hormone （GH） peak concentration below normal］ from endocrine disorders and 21（43.8%） had a family history of short stature. Laboratory tests showed that GH peak concentration following stimulation test was （9.72 ± 7.25） ng/mL， IGF-1 standard deviation score was -0.82 ± 1.42， the difference between bone age and chronological age was -0.93 ± 1.39 years. Of the 25 cases with mutant genes found by WES， 14 （56.0%） had pathogenic mutation， 6 （24.0%） likely pathogenic mutation， and 5 （20.0%） mutation of uncertain significance. Pathogenic and likely pathogenic variants were identified in 14 genes， including 10 affecting intracellular signaling pathways （PTPN11， RAF1， RIT1， ARID1B， ANKRD11， CSNK2A1， SRCAP， CUL7， SMAD4 and FAM111A） and 4 affecting extracellular matrix （ECM） components or functions （ACAN， FBN1， COL10A1 and COMP）. ConclusionsA rare monogenic disease should be considered as the possible etiology for children with severe short stature accompanied by facial anomalies， disproportionate body types， skeletal abnormalities， SGA， GH peak concentration below normal and a family history of short stature. WES played an important role in identifying the monogenic causes of short stature. This study indicated that affecting growth plate cartilage formation through intracellular signaling pathways and ECM components or functions was the main mechanism of causative genes leading to severe short stature in children. Further research may help discover and study new pathogenic variants and gene functions.

Post-traumatic stress disorder (PTSD) is a psychiatric disease that seriously affects brain function. Currently, selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD clinically but have decreased efficiency and increased side effects. In this study, nasal cannabidiol inclusion complex temperature-sensitive hydrogels (CBD TSGs) were prepared and evaluated to treat PTSD. Mice model of PTSD was established with conditional fear box. CBD TSGs could significantly improve the spontaneous behavior, exploratory spirit and alleviate tension in open field box, relieve anxiety and tension in elevated plus maze, and reduce the freezing time. Hematoxylin and eosin and c-FOS immunohistochemistry slides showed that the main injured brain areas in PTSD were the prefrontal cortex, amygdala, and hippocampus CA1. CBD TSGs could reduce the level of tumor necrosis factor-

Objective: To study the preventive effect of Timosaponin BⅡ (T-BⅡ) -loaded temperature/ion-sensitive nasal in situ hydrogels (ISGs) on Alzheimer's disease (AD), its preparation technology, characteristics and in vivo effects were evaluated.Methods: The morphological and rheological properties were evaluated. The preventive effects of T-BⅡ ISG on scopolamine-induced AD in mice were determined with the index of muscarinicreceptor 1 (M1) expression and pathological changes. Results: Results revealed that T-BⅡ ISG significantly increased the content of M1 choline receptors in the hippocampus of mice and ameliorated the damage incurred to the hippocampal cornu ammonis 1 (CA1) area. Conclusion: T-BⅡ ISGs is a reasonable and convenient method of exerting an obvious preventive effect on mice with AD induced by scopolamine. This, thereby, lays forth a new treatment option for preventing AD.

Objective:To investigate the effect of different solutions to prevent nasal intestinal blockage.Methods:Tottaly 199 cases of enteral nutrition treatment were selected from June 2018 to May 2019 and were randomly divided into three groups: warm boiled water group (67 cases), sugar-free cola group (67 cases), alpha-chymotrypsin group (65 cases). The rate of nasointestinal obstruction, the rate of nasointestinal obstruction, the rate of catheter patency maintenance, the rate of recanalization and the incidence of complications in three different enteral nutrition treatment cycles (< 7 days, 7-29 days, ≥ 30 days) were compared.Results:The catheter blockage rate in warm boiled water group was 20.9%(14/67) and in sugar-free cola group was 3.0%(2/67). The patency maintenance time in warm boiled water group was (8.83±1.84)days and in sugar-free cola group was (9.92±1.63) days ( t value was 2.182). The recanalization rate after blockage in warm boiled water group was 21.4%(3/14) and in sugar-free cola group was 100.0%( χ 2 value was 5.021, P < 0.05). The catheter blockage rate in sugar-free cola group was significantly lower than that in warm boiled water group, the catheter maintenance time and recanalization rate after blockage were significantly higher than that in warm boiled water group, the difference was significant ( P < 0.05). There was no significant difference between sugar-free cola group and alpha-chymotrypsin group in catheter blockage rate, catheter blockage rate, recanalization rate after blockage and incidence of complications( P > 0.05). The catheter blockage rate was 0 in patients with enteral nutrition treatment cycle < 7 days. The catheter blockage rate was 11.9%(8/67) (warm boiled water group) , 1.5%(8/67) (sugar-free cola group) and 1.5%(8/67) (alpha-chymotrypsin group) in patients with enteral nutrition treatment cycle 7-29 days. The catheter blockage rate was 9.0%(6/67) (warm boiled water group), 1.5%(1/65, sugar-free cola group) and 3.1%(2/67)(alpha-chymotrypsin group) in patients with enteral nutrition treatment cycle >30 days. The catheter blockage rate in sugar-free cola group and alpha-chymotrypsin group was significantly lower than that in warm boiled water group ( χ 2 values were 4.325-5.836, P<0.05) and there was no significant differences between the sugar-free cola group and the alpha-chymotrypsin group ( P>0.05). Conclusion:Sugar-free cola and alpha-chymotrypsin can effectively reduce the incidence of catheter blockage and complications, prolong the catheter patency and improve the recanalization rate after blockage, especially for patients with enteral nutrition treatment cycle longer than one week.

Objective To analyze the clinical manifestations and gene mutations of rare causes of primary adrenal insufficiency (PAI) in childhood.Methods The clinical features,laboratory tests and gene mutation of 13 patients with PAI in our hospital from September 2010 to August 2017 were analyzed retrospectively.Patients with congenital adrenal hyperplasia,X-linked adrenoleukodystrophy with neurological onset or a clear family history,and autoimmune adrenal insufficiency were excluded.Results The median age of 13 cases (12 males,1 female) was 3 years and 10 months.Medical history or clinical manifestations on the first visit included hyperpigmentation,electrolyte imbalance/salt-wasting crisis,gastrointestinal symptoms,and fatigue,etc.All developments of external genitalia were normal.All cases presented with decreased serum cortisol and increased ACTH levels.Some of the cases showed decreased aldosterone level and plasma renin activity,while 17α-hydroxyprogesterone,testosterone,and androstenedione were in the normal range.Part of cases revealed delayed bone age and adrenal atrophy.Three gene mutations were detected in 13 patients,including NR0B 1 gene (9/13),ABCD 1 gene (3/13),and CYP 11A 1 gene (1/13).NR0B1,and ABCD1 gene mutations were pathogenic mutations,consistent with clinical characteristics.CYP11A1 gene mutation was heterozygote,which cannot fully explain the clinical features.Conclusion PAI in childhood presents common clinical manifestations of adrenal insufficiency,e.g.hyperpigmentation and electrolyte imbalance/sah-wasting crisis,but without specificity.Gene mutational analysis is necessary for precise diagnosis and prognosis estimation.NR0B1 and ABCD1 gene mutations were common in childhood with rare causes of PAI.

Objective Discussion the relationship of PALB2 and AR expression in triple negative breast cancer and its clinical pathological features. Methods The SP immunohistochemical staining was adopted to detect the expression of PALB2 and AR in 178 cases of TNBC, PALB2 divided into two groups according to the expression of different, and to analyze the clinical pathological features and prognostic impact of different AR expression status. Results 178 cases of TNBC, that PALB2 missing expression 47 cases (26.4%), AR expression of 60 cases (33.7%), between of them were negatively correlated (-1≤r<1, P<0.05), in PALB2 negative group, AR expression associated with family history, lymph node metastasis, clinical stage and recurrence and metastasis (P<0.05), and 5-year disease-free survival lower than AR negative expression, Log rank = 4.453, P = 0.035. Conclusion PALB2 negative expression while AR positive expression in TNBC have synergistic effect with disease progression, PALB 2 and AR combined detection may provide a new basis for the prognosis of TNBC interpretation, and recommending take further studies to confirm.

Objective To investigate the changes of thyroid autoantibody(TAA)in children with Turner syndrome(TS),and its association between TAA and thyroid dysfunction,age,karyotype and dyslipidaemia.Methods Thirty-two patients with TS diagnosed by chromosome analysis hospitalized at Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University from July 2007 to July 2015 were divided into 2 groups based on TAA-positive or TAA-negative,then the thyroid dysfunction,the age,the karyotype and the lipid metabolism were compared between 2 groups.Results Of the 23 cases of TAA-positive girls(23/32 cases,71.88％),9 girls(39.13％)suffered from thyroid dysfunction;of the 9 cases of TAA-negative girls(9/32 cases,28.12％),3 girls(33.33％)had thyroid dysfunction.As compared with the girls in TAA-negative group,the age in TAA-positive group was significantly higher[(12.08±2.90)years old vs.(8.89±4.17)years old],and the difference was significant(t=101.500,P=0.047).The patients were divided into 4 age groups:0-5 years old,>5-10 years old,>10-15 years old and >15 years old;the rates with TAA-positive were 25.00％(1/4 cases),75.00％(6/8 cases),82.35％(14/17 cases)and 66.67％(2/3 cases)respectively.Twenty patients received the lipid metabolism test,and 11 cases(11/20 cases,55.00％)of them suffered from dyslipidaemia,9 cases of them were TAA-positive(9/11 cases,81.82％),and 2 cases were TAA-negative(2/11 cases,18.18％).The differences in the prevalence of dyslipidaemia between the 2 groups were significant(x2=4.848,P=0.028).There was no significant difference in the numbers of TAA-positive cases among different karyotypes(x2 =4.246,P=0.120).Conclusions Patients with TS are prone to suffer from thyroid dysfunction and dyslipidaemia.Timely detection of TAA and thyroid function is recommended,as well as the lipid metabolism if necessary.

Objective: This study aimed at determining the characteristics of the glucose homeostasis and its relationship with iron overload of the patients with β-thalassemia major (β-TM). Method: From Sun Yat-sen Memorial Hospital between January 2014 and December 2015, a total of 57 transfusion-dependent β-TM patients with 5-18 years old were enrolled in this study and fasting blood glucose(FBG) and insulin level, serum ferritin (SF), serum iron, transferrin, total iron binding capacity, unsaturated iron binding capacity were determined.Insulin resistance index (IRI), insulin sensitivity index and β-cell function index (BFI) were also estimated. Besides, in 36 patients cardiac T2* and liver T2* were estimated. Result: (1) Four patients(7%) with β-TM were diagnosed diabetes mellitus, and 14(24%) had impaired fasting glucose. (2) The incidence of abnormal glucose metabolism was significantly different according to levels of SF and degrees of the cardiac iron overload(χ²=9.737, P<0.05; χ²=17.027, P<0.05). It rose while the level of SF increased and the degree of cardiac iron overload aggravated. (3) The incidence of abnormal glucose level was not significantly different in cases with different degree of liver iron overload.The severe group of liver iron overload had significantly higher levels of INS, HOMA-βFI, HOMA-ISI, HOMA-βFI than the non-severe group (Z=-2.434, -2.515, F=8.658, all P<0.05), while no differences were found in the level of FBG, HOMA-βFI between two groups. (4) The result of logistic regression analysis indicated that the cardiac T2* was a significant predictor for the incidence of abnormal glucose metabolism in TM patients (P=0.035, OR=1.182%, 95%CI=1.048 to 1.332). Conclusion The high prevalence of abnormal glucose metabolism in β-TM patients was mainly closely related with the internal iron overload, especially in organs.The cardiac T2* was an independent risk factor for the incidence of abnormal glucose metabolism in TM patients.

Background and purpose:Triple-negative breast cancer (TNBC) is currently the focus of breast cancer research. Researches demonstrated that the molecular biological characteristics of different ethnic groups are not the same. This study mainly probed into the expression of endothelial growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in Han and Uygur TNBC patients, and the relationship between the expression and prognosis of patients.Methods:From Jan. 2007 to Jan. 2009, 167 patients were admitted. Among those, 121 were Han and 46 were Uygur patients. The expressions of EGFR, and VEGF were detected by PV-9000 immunohistochemical staining, and compared with lymph node metastasis and clinical staging. The results were analyzed by SPSS 18.0 statistical software.Results:Five-year disease-free survival (DFS) of two groups had no indifferent (P>0.05). EGFR and VEGF positive rate of Han patients was lower than that of Uygur patients (P<0.05). Their expressions were correlated with TNM staging and lymph node metastasis (00.05). Uygur TNBC patients might have a different prognostic factor as compared with Han patients. Further studies need to be carried out.

Objective To detect the expression of Blimp1 gene in MRL/lpr mice,so as to provide new ideas for plasma cell-targeting therapy of systemic lupus erythematosus (SLE).Methods Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation analysis (ChIP) were performed to evaluate the regulatory effect of Blimp1 on B cell maturation antigen (BCMA),and fluorescence-based quantitative PCR was carried out to detect the expression of Blimp1 mRNA in spleen and lymph node tissue of MRL/lpr mice and normal control mice.The intergroup difference in Blimp l mRNA expression was assessed by rank sum test.Results Blimp1 could bind to the BCMA gene promoter.Increased Blimp1 mRNA expression was observed in both the spleen and lymph node tissue of MRL/lpr mice compared with the normal control mice (Z =2.609,3.402,respectively,both P ＜ 0.01).Conclusions BCMA appears to be the target gene of Blimp1,and Blimp1 may plays a certain role in the maintenance of plasma cell survival and antibody production via directly regulating BCMA gene expression.