Objective To analyze serum characteristics and determine the reference range for thyroid function among healthy 11～16 year-old teenagers in Xi'an in order to offer a theoretical basis for clinical diagnosis and therapy.Methods A sum of 1 378 healthy 11～16 year-old teenagers who met the inclusion criteria from the First Affiliated Hospital of the Air Force Medical University(Xijing Hospital)between January 2020 and December 2022 were selected as research subjects,including 628 males and 750 females.They were divided into three groups based on age:Group 1:11～＜13 year-olds(433 cases),Group 2:13～＜15 year-olds(425 cases),and Group 3:15～≤16 year-olds(520 cases).Differences in serum thyroid function indices among different genders and age groups were analyzed,the reference ranges for these indices were established,and 99 healthy 11-16 year-old teenagers who met the inclusion criteria were chosen for verification.Results There were no significant differences between different genders in thyroid stimulating hormone[TSH,2.56(1.80,3.63)μIU/ml vs 2.43(1.68,3.48)μIU/ml]and total thyroxine[TT4,97.84(85.34,111.00)nmol/L vs 98.20(87.16,111.23)nmol/L],the differences were statistically significant(Z=-1.881,-0.638,all P＞0.05).Meanwhile,the differences in free thyroxine[FT4,16.93(15.49,18.60)pmol/L vs 16.26(14.80,17.83)pmol/L],free triiodothyronine[FT3,6.21(5.66,6.80)pmol/L vs 5.59(4.98,6.19)pmol/L],and total triiodothyronine[TT3,2.24(1.96,2.55)nmol/L vs 2.04(1.78,2.34)nmol/L]between different genders were significant(Z=-5.368,-11.994,-6.417 all P＜0.01).The differences in thyroid function indices were significant among different age groups(Z=10.649～261.003,all P＜0.05).The reference ranges for thyroid function indices across different age groups and genders were established,in which thyroid function indicators were verified to be within the established reference range by 99 samples.Conclusion Teenage hormone secretion varies greatly,and the secretion of thyroid hormones is influenced by various factors.Thus,the diagnosis and treatment of teenage thyroid diseases cannot fully rely on the reference ranges provided by adults or manufacturers.This study established the reference range of the thyroid function indices of 11～16 year-old teenagers in Xi'an,offering clinical doctors'diagnosis and treatment data support.

Epilepsy is a common chronic neurological disease, and its comorbidity has attracted more attention.The proportion of epileptic children with mental disorders is also increasing year by year.Among them, children with epilepsy have more depression and anxiety disorders.Repeated seizures can easily cause depression and anxiety, and depression and anxiety can also induce epilepsy, thus the two affect each other.The assessment, screening, diagnosis and intervention of comorbid depression and anxiety in children with epilepsy have become an important part of clinical practice.This review summarized the relationship between epilepsy and depression and anxiety disorders in children, and its research progress on pathogenesis, clinical diagnosis, evaluation and treatment.

Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.

Objective To analyze result of the external quality assessment for laboratories of toxicological pathology diagnosis in organizations in China. Methods A total of 86 organizations that participated in the 2020-2021 external quality assessment in laboratory of toxicological pathology diagnosis (hereinafter referred to as "reference units") were selected as research subjects using convenient sampling method, and the assessment results were analyzed. Results The median of total score was 92, and the 0-100 percentiles were 64-100 in these 86 reference units. Among these reference units, 76 were rated as excellent, 10 as qualified, with the excellent and the qualified rate of 88.4% and 11.6%, respectively. No reference unit was rated as unqualified. The rates of excellence of the reference units in public health institutions, pharmaceutical research institutions, drug safety evaluation centers and testing companies were 95.7%, 84.2%, 85.7% and 86.7%, and the qualified rates were 4.3%, 15.8%, 14.3% and 13.3%, respectively. The distribution of excellence and qualification among the four types of reference units showed no statistical difference (P>0.05). The distribution of sample scores according to the three grades of poor, good, and excellent were 4.9%, 20.7%, and 74.5% in public health institutions, 8.6%, 23.7%, and 67.8% in pharmaceutical research institutions, 12.5%, 25.0%, and 62.5% in drug safety evaluation centers, and 5.4%, 17.5%, and 77.1% in testing companies. The proportion of excellence unit in public health institutions was higher than that in pharmaceutical research institutions (P<0.05). Conclusion The overall toxicological pathology diagnostic capabilities in China are good, and various types of reference units demonstrate comparable technical capabilities. However, there is a need for standardization of diagnostic terminology.

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.

Sphingomyelinases (SMase) are the main enzymes that regulate the signaling pathway of sphingomyelin and the metabolism of related products, and they are involved in the key steps of the complex metabolic process of sphingomyelin. In recent years, many studies have shown that SMase is involved in the biological processes such as cell cycle arrest, cell migration, and inflammation and promotes the development and progression of hepatocellular carcinoma by regulating the apoptosis and proliferation of tumor stem cells. SMase has an important potential biological value in the development, progression, diagnosis, and treatment of hepatocellular carcinoma. This article summarizes the exact role of SMase in the development and progression of hepatocellular carcinoma, in order to provide new ideas and strategies for the clinical treatment of hepatocellular carcinoma and the development of new drugs.

Objective:To investigate the effects of long non-coding RNA (lncRNA) Gm13568 on the activation of A1 astrocytes and the progress of experimental autoimmune encephalomyelitis (EAE) in mice.Methods:A recombinant lentiviral vector (LV-Inhibit-Gm13568) carrying astrocyte-specific promoter of glial fibrillary acidic protein (GFAP) was established to inhibit the function of endogenous Gm13568. A control vector (LV-ctrl) was established as well. The recombinant vectors were packaged. C57BL/6 mice were injected with 1×10 7 transforming units of viral suspension via the tail vein and 7 d after the injection, myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) was used to establish the mouse model of EAE. Four groups, PBS group, EAE group, LV-ctrl+ EAE group and LV-Inhibit-Gm13568+ EAE group, were included in this study. Clinical signs of the mice were monitored daily in a double-blinded manner. The mice were sacrificed 23 d after the EAE model was established and the spinal cord tissues were collected. The expression of Serping 1, C3, Srgn and H2-T23 at mRNA level was detected by real-time PCR. Changes in the expression of IL-6, TNF-α, macrophage chemotactic protein-1 (MCP-1) and interferon-inducible protein-10 (IP-10) were measured. Western blot was used to investigate the expression of GFAP and Notch1 in spinal cord tissues and the phosphorylation of signal transduction and transcription activator 3 (STAT3). The expression of Notch1 intracellular domain (NICD) and GFAP in spinal cord tissues was detected by immunofluorescence. Furthermore, the infiltration of inflammatory cells and the demyelination of spinal cord were observed using HE and Luxol fast blue (LFB) staining methods. Results:Compared with PBS group, A1 astrocytes were activated and Notch1 expression was significantly up-regulated in EAE group and LV-ctrl+ EAE group. The clinical score of mice in LV-Inhibit-Gm13568+ EAE group was decreased from an average score of 3.5 to less than 1 on 23 d after antigen induction and the clinical symptoms were alleviated as compared with the mice in LV-ctrl+ EAE group. Meanwhile, the activation of A1 astrocytes was down-regulated, and the production of inflammatory cytokines and chemokines was also reduced. The expression of Notch1, GFAP and NICD at protein level and the phosphorylation of STAT3 were significantly reduced. Moreover, the infiltration of inflammatory cells and demyelination of spinal cord tissues were alleviated significantly.Conclusions:LncRNA Gm13568 might regulate the activation of A1 astrocytes via the Notch1/STAT3 pathway, thus affecting the production of inflammatory cytokines and chemokines and participating in the process of EAE.

This study reported a family of mitochondrial diabetes mellitus complicated with chronic hereditary pancreatitis. A 18-year-old woman presented with self-reported hyperglycemia and chronic epigastric pain was admitted to our hospital. Clinical data and family history were collected. Mitochondrial gene sequencing and whole exon gene sequencing showed that the proband carried mutation of mt.3243A>G and heterozygous mutation of SPINK1 c. 194+ 2T>C, which was considered as mitochondrial diabetes mellitus with chronic pancreatitis.

Objective: To investigate the effect of peroxiredoxin 2 (Prx2) overexpression on fibroblast proliferation and collagen synthesis induced by transforming growth factor-β1 (TGF-β1) . Methods: Fibroblasts were randomly divided into control group (DMEM medium) , TGF-β1 group (5 μg/L TGF-β1) , negative control group (treated with 5 μg/L TGF-β1 and transfected with empty lentiviral vector) , and Prx2 group (treated with 5 μg/L TGF-β1 and transfected with Prx2 overexpression lentiviral vector) . MTT assay was used to measure cell proliferation, immunofluorescence assay was used to measure the expression of 8-OHdG, and Western blot was used to measure the expression of p-JNK, p-P38, collagen type I, collagen type III, and Prx2. SPSS 18.0 was used for statistical analysis. The continuous data were expressed as mean±standard deviation; an analysis of variance was used for comparison between groups, and the least significant difference t-test was used for further comparison between two groups. Results: Lentiviral transfection was performed successfully, and the Prx2 group had a significant increase in the protein expression of Prx2 (P<0.05) . Compared with the control group, the TGF-β1 group had a significant increase in the proliferation ability (P<0.05) , and compared with the TGF-β1 group, the Prx2 group had a significant reduction in the proliferation ability (P<0.05) . Compared with the control group, the TGF-β1 group had significant increases in the expression of 8-OHdG, p-JNK, p-P38, collagen type I, and collagen type III (P<0.05) ; compared with the TGF-β1 group, the negative control group had no significant changes in the expression of 8-OHdG, p-JNK, p-P38, collagen type I, and collagen type III (P>0.05) , while the Prx2 group had significant reductions in the above parameters (P<0.05) . Conclusion Prx2 overexpression inhibits fibroblast proliferation and collagen synthesis induced by TGF-β1 through inhibiting reactive oxygen species and activating the JNK and P38 pathways.

Objective: This study was carried out to analyze the clinical characteristics of pseudohypopara-thyroidism(PHP) type 1b, and to improve the understanding and diagnosis of the disease. Methods: Five patients with molecular diagnosis of pseudohypoparathyroidism type 1b in our hospital during 2018 were enrolled, their clinical data, biochemical indicators, imaging, and gene detection results were analyzed. Results: There were 4 females and 1 male, with low calcium, high phosphorus and high PTH serum concentrations. The onset age span was large and the onset symptoms were different. Family history may not be obvious. There was abnormal methylation of GNAS gene or deletion of exon STX16 in methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) detection while gene sequencing result was negative. Conclusion MS-MLPA detection was still needed in patients with suspected PHP but negative gene sequencing result. Different methylation abnormalities and copy number variations might be correlated with the onset symptoms and familial of type 1b PHP.