Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.

Systems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans. Whether such signatures are similar across multiple seasons and in diverse populations is unknown. We applied systems approaches to study immune responses in young, elderly, and diabetic subjects vaccinated with the seasonal influenza vaccine across five consecutive seasons. Signatures of innate immunity and plasmablasts correlated with and predicted influenza antibody titers at 1 month after vaccination with >80% accuracy across multiple seasons but were not associated with the longevity of the response. Baseline signatures of lymphocyte and monocyte inflammation were positively and negatively correlated, respectively, with antibody responses at 1 month. Finally, integrative analysis of microRNAs and transcriptomic profiling revealed potential regulators of vaccine immunity. These results identify shared vaccine-induced signatures across multiple seasons and in diverse populations and might help guide the development of next-generation vaccines that provide persistent immunity against influenza.

Monovalent, bivalent and biparatopic nanobodies targeting S1 protein of porcine epidemic diarrhea virus efficiently neutralized the virus infectivity.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea and death in neonatal piglets, which has brought huge economic losses to the pork industry worldwide since its first discovery in the early 1970s in Europe. Passive immunization with neutralizing antibodies against PEDV is an effective prevention measure. To date, there are no effective therapeutic drugs to treat the PEDV infection. RESULTS: We conducted a screening of specific nanobodies against the S1 protein from a phage display library obtained from immunized alpacas. Through competitive binding to antigenic epitopes, we selected instead of chose nanobodies with high affinity and constructed a multivalent tandem. These nanobodies were shown to inhibit PEDV infectivity by the neutralization assay. The antiviral capacity of nanobody was found to display a dose-dependent pattern, as demonstrated by IFA, TCID50, and qRT-PCR analyses. Notably, biparatopic nanobody SF-B exhibited superior antiviral activity. Nanobodies exhibited low cytotoxicity and high stability even under harsh temperature and pH conditions, demonstrating their potential practical applicability to animals. CONCLUSIONS: Nanobodies exhibit remarkable biological properties and antiviral effects, rendering them a promising candidate for the development of anti-PEDV drugs.

Systems biology of vaccination for seasonal influenza in humans.

Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons. We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). TIV induced higher antibody titers and more plasmablasts than LAIV did. In subjects vaccinated with TIV, early molecular signatures correlated with and could be used to accurately predict later antibody titers in two independent trials. Notably, expression of the kinase CaMKIV at day 3 was inversely correlated with later antibody titers. Vaccination of CaMKIV-deficient mice with TIV induced enhanced antigen-specific antibody titers, which demonstrated an unappreciated role for CaMKIV in the regulation of antibody responses. Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.

Evaluation of immunogenicity of gene-deleted and subunit vaccines constructed against the emerging pseudorabies virus variants.

BACKGROUND: Pseudorabies (PR) (also called Aujeszky's disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of pseudorabies virus (PRV) since 2011 has led to PR outbreaks in China and a vaccine that antigenically more closely matches these PRV variants could represent an added value to control these infections. METHODS: The objective of this study was to develop new live attenuated and subunit vaccines against PRV variant strains. Genomic alterations of vaccine strains were based on the highly virulent SD-2017 mutant strain and gene-deleted strains SD-2017ΔgE/gI and SD-2017ΔgE/gI/TK, which constructed using homologous recombination technology. PRV gB-DCpep (Dendritic cells targeting peptide) and PorB (the outer membrane pore proteins of N. meningitidis) proteins containing gp67 protein secretion signal peptide were expressed using the baculovirus system for the preparation of subunit vaccines. We used experimental animal rabbits to test immunogenicity to evaluate the effect of the newly constructed PR vaccines. RESULTS: Compared with the PRV-gB subunit vaccine and SD-2017ΔgE/gI inactivated vaccines, rabbits (n = 10) that were intramuscularly vaccinated with SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine showed significantly higher anti-PRV-specific antibodies as well as neutralizing antibodies and IFN-γ levels in serum. In addition, the SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine protected (90-100%) rabbits against homologous infection by the PRV variant strain. No obvious pathological damage was observed in these vaccinated rabbits. CONCLUSIONS: The SD-2017ΔgE/gI/TK live attenuated vaccine provided 100% protection against PRV variant challenge. Interestingly, the subunit vaccines with gB protein linked to DCpep and PorB protein as adjuvant may also be a promising and effective PRV variant vaccine candidate.

Relationship between serum fibroblast growth factor 19 and vascular endothelial growth factor and soluble klotho protein in type 1 diabetic children.

BACKGROUND: Fibroblast growth factor 19 (FGF19) takes part in maintaining the balance of glycolipids and may be involved in complications of type 1 diabetes(T1D) in children. This study aimed at at evaluating the relationship among the levels of serum FGF19 and vascular endothelial growth factor(VEGF)and soluble klotho protein(sklotho) in type 1 diabetic children. METHODS: In a cross-section single center study samples were obtained from 96 subjects: 66 T1D and 30 healthy children.Serum FGF19 and VEGF and sklotho concentrations were measured by ELISA. And 66 type 1 diabetes participants were divided into two groups according to T1D duration or three groups according to HbA1c.Furthermore,we compared the serum levels of FGF19 and VEGF and sklotho in different groups. RESULTS: The concentration of FGF19 was lower in T1D than in the controls(226.52 ± 20.86pg/mu vs.240.08 ± 23.53 pg/L, p = 0.03),while sklotho was also lower in T1D than in the controls (2448.67 ± 791.92pg/mL vs. 3083.55 ± 1113.47pg/mL, p = 0.011). In contrast, VEGF levels were higher in diabetic patients than in controls (227.95 ± 48.65pg/mL vs. 205.92 ± 28.27 pg/mL, p = 0.016). In T1D, FGF19 and VEGF and sklotho was not correlated with the duration of diabetes. FGF19 and VEGF and sklotho were correlated with HbA1c (r=-0.349, p = 0.004 and r = 0.302, p = 0.014 and r=-0.342, p = 0.005, respectively), but not with blood glucose and lipid. Among subjects in the T1D group, concentrations of FGF19,VEGF and sklotho protein were different between different groups according to the degree of HbA1c(P < 0.005).Furthermore, there was a positive correlation between the serum FGF19 concentration and sklotho levels (r = 0.247,p = 0.045), and a negative correlation between the serum FGF19 concentration and VEGF level(r=-0.335,P = 0.006). CONCLUSIONS: The serum FGF19 levels have a close relation with serum VEGF levels and sklotho levels among T1D subjects. FGF19 may be involved in the development of complications in children with type 1 diabetes through interaction with VEGF and sklotho.

Comparative proteomic analysis of PK15 swine kidney cells infected with a pseudorabies pathogenic variant and the Bartha-K/61 vaccine strain.

Pseudorabies virus (PRV) is the causative agent of Aujeszky's disease and is communicable across species. In particular, the emergence of PRV variants in 2011 have resulted in serious economic losses to the Chinese pig industry. In this study, we used tandem mass tag (TMT) quantitative protein analysis to identify differentially expressed proteins between the PRV variant strain SD-2017 and the vaccine strain Bartha-K/61 in the swine kidney cell line PK15. Overall, we identified 4690 proteins for SD-2017 infection compared with the mock-infected control cells. We found 162 differentially expressed cellular proteins including 41 up- and 121 down-regulated proteins. SD-2017-infected PK15 cells differential proteins were primarily related to gap junctions, the phagosome, antigen processing and presentation, cell adhesion molecules and peroxisome pathways. Compared to Bartha-K/61-infected PK15 cells, SD-2017-infected cells displayed differentially expressed proteins involved in tryptophan metabolism, mitophagy and Notch signaling. Western blot analysis of MARK2, TSR1 and TMED1 three representative proteins validated the reliability of the TMT data. This study is an initial at-tempt to compare the proteomes of PK15 cells infected by a PRV variant and a vaccine strain using TMT technology to provide new insights into the mechanisms of PRV pathogenesis and immune evasion.

ABCC8-related maturity-onset diabetes of the young: Clinical features and genetic analysis of one case.

OBJECTIVE: To confirm the diagnosis of a 13-year-old adolescent with familial diabetes and further examine his genetic pathogeny. RESEARCH DESIGN AND METHODS: Clinical data were collected, and genetic examination was performed. PolyPhen-2 and Mutation Taster were used to predict the deleterious effects of the variant. Clustal Omega software was used to confirm the conservation of amino acid substitutions. To examine changes in the expression of proteins, recombinant vectors were constructed, and the expression of wild-type and variant target genes was detected through quantitative polymerase chain reaction. Furthermore, the wild-type and variant eukaryotic recombinant vectors were treated with a ubiquitin degradation inhibitor (MG132) and a lysosomal degradation pathway inhibitor (CQ, 3-mA). The expression of target proteins was detected through Western blot analysis. RESULTS: The patient had hyperglycaemia (27 mmol/L), a high HbA1c level (13.1%), a decreased C-peptide level (0.63 ng/ml) and no diabetes antibodies. The patient had a family history of diabetes. The novel variation of ABCC8 c.2477G>A was detected in the proband and his relatives. The mutation was predicted to be harmful. Changes in the protein structure were observed. The ABCC8 c.2477G >A variant resulted in an increase in ABCC8 expression. Furthermore, changes in the expression of the ABCC8 variant was observed after 3-MA treatment, especially after treatment with MG132. At the follow-up, the patient's glucose level was normal without drug therapy for more than 2 years until until he started taking Trelagliptin Succinate to control hyperglycemia within the recent 6 months. CONCLUSIONS: The diagnosis of maturity-onset diabetes of the young (MODY)12 was confirmed in our patient. The ABCC8 variant inhibited both ubiquitination and autophagy lysosome degradation pathways, especially the ubiquitination degradation pathway.

LamB, OmpC, and the Core Lipopolysaccharide of Escherichia coli K-12 Function as Receptors of Bacteriophage Bp7.

Bp7 is a T-even phage with a broad host range specific to Escherichia coli, including E. coli K-12. The receptor binding protein (RBP) of bacteriophages plays an important role in the phage adsorption process and determines phage host range, but the molecular mechanism involved in host recognition of phage Bp7 remains unknown. In this study, the interaction between phage Bp7 and E. coli K-12 was investigated. Based on homology alignment, amino acid sequence analysis, and a competitive assay, gp38, located at the tip of the long tail fiber, was identified as the RBP of phage Bp7. Using a combination of in vivo and in vitro approaches, including affinity chromatography, gene knockout mutagenesis, a phage plaque assay, and phage adsorption kinetics analysis, we identified the LamB and OmpC proteins on the surface of E. coli K-12 as specific receptors involved in the first step of reversible phage adsorption. Genomic analysis of the phage-resistant mutant strain E. coli K-12-R and complementation tests indicated that HepI of the inner core of polysaccharide acts as the second receptor recognized by phage Bp7 and is essential for successful phage infection. This observation provides an explanation of the broad host range of phage Bp7 and provides insight into phage-host interactions.IMPORTANCE The RBPs of T4-like phages are gp37 and gp38. The interaction between phage T4 RBP gp37 and its receptors has been clarified by many reports. However, the interaction between gp38 and its receptors during phage adsorption is still not completely understood. Here, we identified phage Bp7, which uses gp38 as an RBP, and provided a good model to study the phage-host interaction mechanisms in an enterobacteriophage. Our study revealed that gp38 of phage Bp7 recognizes the outer membrane proteins (OMPs) LamB and OmpC of E. coli K-12 as specific receptors and binds with them reversibly. HepI of the inner-core oligosaccharide is the second receptor and binds with phage Bp7 irreversibly to begin the infection process. Determining the interaction between the phage and its receptors will help elucidate the mechanisms of phage with a broad host range and help increase understanding of the phage infection mechanism based on gp38.

Early diagnosis and post-operative follow-up of 50 Chinese children with craniopharyngioma.

BACKGROUND: Craniopharyngioma is a relatively common congenital intracranial tumour for children. But only few available studies focused on the endocrine evaluation before diagnosis and post-operative endocrine evaluations of children with craniopharyngioma. AIM: This study aims to aid in the early diagnosis of craniopharyngioma (CP) and follow-up post-operative children suffered from craniopharyngioma. METHODS: Craniopharyngioma patients, as the CP group (n = 50), and healthy children, as the control group (n = 30), the symptoms and pituitary hormone levels were reviewed and investigated. RESULTS: The pre-operative levels of peak of GH, IGF-1, FT4, ACTH, COR and PRL of CP patients were significantly lower than those of the control group (all the P ≤ 0.001). Levels of pituitary-hormones after surgery were significantly lower than both those before surgery and those of the control group (all the P ≤ 0.001). HGH treatment could significantly improve the growth velocity of post-operative children (3.8 ± 1.5 cm/year vs 13.0 ± 3.4 cm/year for males, P ≤ 0.001; 4.0 ± 1.3 cm/year vs 12.7 ± 1.8 cm/year for females, P ≤ 0.001). CONCLUSIONS: Children presenting with endocrine disturbance symptoms combined with pituitary hormone deficits should be assessed by MRI to exclude craniopharyngioma earlier. Also, long-term follow-up study was very essential to craniopharyngioma survivors.

[Analysis of pathogenic variants in a Chinese pedigree affected with hyaline fibromatosis syndrome].

OBJECTIVE: To explore the clinical characteristics and genetic basis for a pair of twins affected with hyaline fibromatosis syndrome (HFS). METHODS: Clinical data of the twins were retrospectively analyzed. High-throughput sequencing was carried out to detect potential pathogenic variants. CLUSTALX was employed to analyze cross-species conservation of the mutant amino acids. Impact of the mutations was predicted by using software including PolyPhen-2 and Mutation taster. RESULTS: The pair of twins have featured growth and intelligence retardation, and were found to carry compound heterozygous variants of the ANTXR2 gene including c.1214G>A and c.1074delT, among which c.1214G>A was unreported previously. Both variants were predicted to be pathogenic. In addition to growth and mental delay, the pair of twins also featured hyperplasia of the gum and soft tissue-like masses of the auricle. The younger brother had rupture of the auricle mass during follow-up. CONCLUSION: The patients' condition can probably be attributed to the compound heterozygous variants of the ANTXR2 gene. Above finding has facilitated molecular diagnosis of the patients.

Decontamination of face masks with steam for mask reuse in fighting the pandemic COVID-19: Experimental supports.

The coronavirus disease 2019 pandemic caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has claimed many lives worldwide. Wearing medical masks (MMs) or N95 masks ([N95Ms] namely N95 respirators) can slow the virus spread and reduce the infection risk. Reuse of these masks can minimize waste, protect the environment, and help solve the current imminent shortage of masks. Disinfection of used masks is needed for their reuse with safety, but improper decontamination can damage the blocking structure of masks. In this study, we demonstrated using the avian coronavirus of infectious bronchitis virus to mimic SARS-CoV-2 that MMs and N95Ms retained their blocking efficacy even after being steamed on boiling water for 2 hours. We also demonstrated that three brands of MMs blocked over 99% viruses in aerosols. The avian coronavirus was completely inactivated after being steamed for 5 minutes. Altogether, this study suggested that MMs are adequate for use on most social occasions and both MMs and N95Ms can be reused for a few days with steam decontamination between use.

Potential utilities of mask-wearing and instant hand hygiene for fighting SARS-CoV-2.

The surge of patients in the pandemic of COVID-19 caused by the novel coronavirus SARS-CoV-2 may overwhelm the medical systems of many countries. Mask-wearing and handwashing can slow the spread of the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real-time reverse transcription-polymerase chain reaction. Previous studies on mask-wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four-layer kitchen paper and one-layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask-wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask-wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID-19. Collectively, a simple approach to slow the exponential spread of SARS-CoV-2 was proposed with the support of experiments, literature review, and control experiences.

Determinants of deranged thyroid function parameters in children admitted for management of diabetic ketoacidosis/diabetic ketosis.

BACKGROUND: Euthyroid sick syndrome (ESS) frequently arises in children admitted with diabetic ketoacidosis/diabetic ketosis (DKA/DK). This study evaluates the interplay of various metabolic factors with occurrence of deranged thyroid function tests in children suffering from DKA/DK. METHODS: 98 DKA and 96 DK pediatric patients were selected from hospital records. Those on thyroxine replacement, with overt hypothyroidism, or with positive anti-thyroperoxidase (TPO) antibody were excluded. Tests for liver function, renal function, lipid profile, serum osmolarity, thyroid function, c-peptide levels, and glycosylated hemoglobin were done on all patients. Children were divided into euthyroid (n = 88) and ESS groups (n = 106). RESULTS: The ESS group had a higher level of white blood cell count (WBC), plasma glucose (PG), beta-hydroxybutyric acid (ß-HB), triglyceride (TG), anion gap (AG), glycosylated hemoglobin (HbA1c) and a lower level of HCO3-, prealbumin (PA), and albumin (ALB) compared with the euthyroid group (P < 0.05). Free T3 (FT3) levels were significantly correlated to ß-HB, HCO3-, AG, PA, and HbA1c (r = - 0.642, 0.681, - 0.377, 0.581, - 0.309, respectively; P < 0.01). Free T4 (FT4) levels were significantly correlated to ß-HB, HCO3-, and ALB levels (r = - 0.489, 0.338, 0.529, respectively; P < 0.01). TSH levels were significantly affected by HCO3- only (r = - 0.28; P < 0.01). HCO3- level was the most important factor deciding euthyroid or ESS on logistic regression analysis (OR = 0.844, P = 0.004, 95%CI = 0.751-0.948). CONCLUSIONS: Lower levels of free thyroid hormones and occurrence of ESS were associated with a higher degree of acidosis in children with DKA/DK.

[Efficacy of letrozole in treatment of children with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency].

OBJECTIVE: To assess the efficacy of letrozole in treatment of children with congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency (21-OHD). METHODS: Twenty eight children, including 19 boys and 9 girls aged 4-10y, with CAH due to 21-OHD were enrolled in the study. At the first six months of study, all children received conventional treatment with hydrocortisone or fludrocortisone, then letrozole was added to original regimen. The height velocity (HV), difference between bone age and chronological age (BA-CA), height standard diviation score based on bone age (HtSDS BA), predicted adult height (PAH), Tanner phase, sex hormone, and possible adverse reaction were evaluated and compared between those before and after letrozole treatment. RESULTS: After 6 months of letrozole treatment, there was significant deceleration of HV, but it would recover soon. There was significant increase of HtSDS BA after 12 months of letrozole treatment ( P < 0.05 or P < 0.01), and significant changes in BA-CA after 18 months of letrozole treatment ( P < 0.05). PAH of female children was significantly increased during letrozole treatment ( P < 0.05), whereas PAH of male children was significantly increased 18 months after letrozole treatment ( P < 0.05). Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were significantly increased, but did not meet the diagnostic criteria of central precocious puberty. Estradiol was significantly decreased ( P < 0.01), but no changes in testosterone level was observed. During 24 months letrozole treatment, no hirsutism, severe acne, headache, bone pain, obesity, hypertension, rash and other adverse reactions were observed. CONCLUSIONS: Letrozole can delay bone maturation and improve PAH, which can be used with conventional treatment for children with CAH due to 21-OHD, especially for those with high BA and low PAH.

Unique characteristics of CpG island methylator phenotype (CIMP) in a Chinese population with colorectal cancer.

BACKGROUND: Molecular characteristics of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been well documented in Western, but not in Chinese, populations. METHODS: We investigated the incidence of CIMP, BRAF/KRAS mutation, and microsatellite instability (MSI) in a Chinese population with CRC (n = 401) and analysed associations between CIMP status and clinicopathological and molecular features. RESULTS: A total of 41 cases, 310 cases, and 40 cases were classified as CIMP-high, CIMP-low, and CIMP-negative, respectively. We detected a significantly low incidence of BRAF mutation in adenomas (2%) and CRC (0.7%), and a relatively low incidence of KRAS mutation (24.9%) compared with that in other populations. We also detected a relatively low incidence of CIMP-high (10.2%), which was significantly associated with younger age (≤49 years of age), female sex, and proximal tumour location. CONCLUSIONS: This study revealed unique characteristics of CIMP in a Chinese population with colorectal cancer. Developing specific CIMP markers based on unique populations or ethnic groups will further help to fully elucidate CIMP pathogenesis.

Distinct pituitary hormone levels of 184 Chinese children and adolescents with multiple pituitary hormone deficiency: a single-centre study.

BACKGROUND: Pituitary tumors and/or their treatment are associated with multiple pituitary hormone deficiency (MPHD) in adults, but the distinct pituitary hormone profile of MPHD in Chinese children and adolescents remains unclear. METHODS: Patients with MPHD were divided into four groups according to their MRI results: 1) pituitary stalk interruption syndrome (PSIS); 2) hypoplasia; 3) normal; and 4) tumor survivor. RESULTS: Among the 184 patients, 93 patients (50.5%) were with PSIS, 24 (13.0%) had hypoplastic pituitary gland, 10 (5.4%) patients were normal, and 57 (31.0%) were tumor survivors. There was an association between abnormal fetal position and PSIS (P ≤ 0.001). The CA/BA in PSIS, hypoplasia, normal, tumor survivor groups were 2.27 ± 1.05, 1.48 ± 0.39, 1.38 ± 0.57, 1.49 ± 0.33, and HtSDS were - 3.94 ± 1.39, - 2.89 ± 1.09, - 2.50 ± 1.05, - 1.38 ± 1.63. Patients in PSIS group had the largest CA/BA (P ≤ 0.001 vs. hypoplasia group, P = 0.009 vs. normal group, P ≤ 0.001 vs. tumor survivors) and lowest HtSDS (P ≤ 0.001 vs. hypoplasia group, P = 0.003 vs. normal group, P ≤ 0.001 vs. tumor survivors). The levels of TSH in the PSIS, hypoplasia, normal, and tumor survivor groups were 1.03 ± 1.08 (P = 0.149 vs. tumor survivors), 1.38 ± 1.47 (P = 0.045 vs. tumor survivors), 2.49 ± 1.53 (P < 0.001 vs. tumor survivors), and 0.76 ± 1.15 µIU/ml. The levels of GH peak in PSIS, hypoplasia, normal, tumor survivor groups were 1.37 ± 1.78, 1.27 ± 1.52, 3.36 ± 1.79, 0.53 ± 0.52 ng/ml and ACTH were 27.50 ± 20.72, 25.05 ± 14.64, 34.61 ± 59.35, 7.19 ± 8.63 ng/ml. Tumor survivors had the lowest levels of GH peak (P ≤ 0.001 vs. PSIS group, P = 0.002 vs. hypoplasia group, P ≤ 0.001 vs. normal group) and ACTH (all the P ≤ 0.001 vs. the other three groups). CONCLUSION: The frequency of PSIS is high among children and adolescents with MPHD. The severity of hormone deficiencies in patients with MPHD was more important in the tumor survivor group compared with the other groups.

CYP24A1 Variants in Two Chinese Patients with Idiopathic Infantile Hypercalcemia.

BACKGROUND: Biallelic pathogenic variants in CYP24A1 can cause idiopathic infantile hypercalcemia (HCINF). METHODS: We report 2 additional molecular abnormalities in 2 Chinese children with CHINF1. RESULTS: Biallelic variants in CYP24A1 were found in two patients. Patient One was compound heterozygous for c.449 + 1G > T and c.1426_1427delCT. Patient Two was compound heterozygous for c.1310C > A and c.1426_1427delCT. The c.1310C > A and c.449 + 1G > T were two different novel CYP24A1 variants. Multiple computational tools predicted that both impact protein function. A total of 36 variants have been previously reported in patients with HCINF1, of which 27 were classified as pathogenic or likely pathogenic and nine as uncertain clinical significance. CONCLUSION: Genetic tests are helpful in order to counsel the susceptible individuals to avoid vitamin D and take preventive measures in order to avoid complications.

Risk factors and complications of small for gestational age.

OBJECTIVE: The objective of this study was to find out the maternal risk factors and perinatal complications in small for gestational age (SGA) newborns. METHODS: A total of 181 SGA cases and 1299 cases of appropriate for gestational age (AGA) with the same gestational age between January 2015 and December 2016 were enrolled in Linyi People's Hospital, China. The risk factors were analyzed and the frequencies of perinatal complications were compared between the two groups. RESULTS: The frequencies of maternal risk factors such as pregnancy-induced hypertension, abnormal placenta and twins in the SGA group were significantly higher than that in the AGA group (P<0.05). The incidence of hyperbilirubinemia and hypoglycemia in the perinatal period was also higher in the SGA newborns group (P<0.05), while there were no significant differences in the incidence of pneumonia, apnea, septicemia, intracranial hemorrhage, neonatal asphyxia, congenital malformations, hypoxic-ischemic encephalopathy, respiratory distress syndrome and necrotizing enterocolitis between the two groups. CONCLUSIONS: SGA can cause perinatal complications including neonatal hypoglycemia and hyperbilirubinemia. It is necessary to strengthen the perinatal monitoring and antenatal care to reduce SGA and the perinatal complications of SGA.

The association of insulin-like growth factor-1 standard deviation score and height in Chinese children with type 1 diabetes mellitus.

Assessing the relationship between IGF-1 and height in type 1 diabetes children. Seventy-two type 1 diabetes children and 190 controls were recruited. The height standard deviation score of type 1 diabetes children was significantly higher than controls. The height standard deviation score was higher than the target height standard deviation score in both type 1 diabetes and controls. Serum IGF-1 levels and the IGF-1 standard deviation score were significantly lower in type 1 diabetes patients compared with controls. There was a significant difference in IGF-1 standard deviation score between the good glycemic control group and control group. The height standard deviation score was significantly correlated with C-peptide and IGF-1 levels. Furthermore, the IGF-1 standard deviation score was significantly correlated with glycemic control and C-peptide. The growth hormone/IGF-1 axis is impaired in type 1 diabetes, but height with good or poor glycemic control is not impaired.

Effects of recombinant human growth hormone administration on cardiovascular risk factors in obese children with relative growth hormone deficiency.

BACKGROUND: Based on the sample of obese children with relative growth hormone deficiency (GHD), the objective of our study was to determine the effects of rhGH treatment on cardiovascular risk factors, including body mass index (BMI), lipid levels and glucose metabolism index. METHODS: A total of 43 obese children with relative GHD were included in our final analysis. The obese subjects were divided into two groups: recombinant human growth hormone (rhGH) treatment group and untreated control group. RESULTS: After 6 months, subjects in the rhGH treatment group had significant reductions in BMI standard deviation scores (SDS) compared with controls (2.32 ± 0.85 vs. 2.80 ± 0.61; P = 0.041), and Insulin-like growth factor 1(IGF-1) level increased during rhGH treatment, in comparison with the control group (702.91 ± 246.03 vs. 348.30 ± 131.93 ng/mL, P < 0.001). GH treatment reduced low density lipoprotein cholesterol (LDL-C) (2.20 ± 0.45 vs. 2.63 ± 0.76 mmol/L, P = 0.027), aspartate aminotransferase (AST) (21.26 ± 5.72 vs. 32.30 ± 17.68 mmol/L, P = 0.006) as well as alanine aminotransferase (ALT) (16.70 ± 6.72 vs. 45.20 ± 46.62 mmol/L, P = 0.002), and increased high density lipoprotein cholesterol (HDL-C) (1.45 ± 0.40 vs. 1.19 ± 0.23 mmol/L, P = 0.016) levels compared with the control group. CONCLUSION: RhGH treatment for 6 months on obese children with relative GHD reduces BMI SDS, stabilize IGF-1 levels, and exerts beneficial effects on blood lipid profiles and live enzyme compared with untreated control group. Moreover, GH administration has no significant effects on increased insulin resistance and no adversely effect on glucose homeostasis.