Retrospective analysis of 23 Chinese children with congenital hyperinsulinism undergoing pancreatectomy.

INTRODUCTION: The aim of the study was to discuss therapeutic effect and prognosis of pancreatectomy in the treatment of congenital hyperinsulinism (CHI). MATERIAL AND METHODS: A total of 23 Chinese children with CHI, who had undergone pancreatectomy, were selected as the study objects. The clinical data, the results of the ¹8Fluoro-L-3-4 dihydroxyphenylalanine positron emission tomography/computerized tomography (¹8F-DOPA PET/CT) scanning, and the diagnosis, treatment, and follow-up were analysed retrospectively. RESULTS: Among the 23 cases, 14 patients were diagnosed with focal-type CHI via a ¹8F-DOPA PET/CT scan prior to the operation, with the lesions removed via partial pancreatectomy. After the operation, ten patients (71%) had normal blood glucose levels, while frequent feeding was required in four patients (29%) to control the hypoglycaemia. Three cases were diagnosed as diffuse-type CHI via preoperative scanning, two of which were treated by subtotal pancreatectomy. The other case was treated by near-total pancreatectomy, and the blood glucose level was normal following the operation. The remaining six cases were not diagnosed via the pancreatic scanning prior to the operation due to the limitation of certain conditions. Here, pancreatectomy was performed directly due to severe hypoglycaemia. CONCLUSIONS: ¹8F-DOPA PET/CT scanning was a reliable method for determining the histological type and localizing the lesion before the operation. Partial pancreatectomy for focal-type CHI had a high cure rate.

Analysis of clinical and genetic characteristics of Chinese children with congenital hyperinsulinemia that is spontaneously relieved.

OBJECTIVE: This study aimed to analyze the clinical and genetic characteristics of Chinese children with congenital hyperinsulinemia (CHI) that is spontaneously relieved. METHODS: The patient group comprised 200 children with CHI that were treated at the Beijing Children's Hospital from January 2006 to December 2018. The patients were divided into two groups according to their prognosis: the spontaneous remission group (n = 92) and the nonspontaneous remission group (n = 108). The clinical characteristics, pathogenic genes, diagnosis and treatment process, and follow-up data of both groups were analyzed retrospectively. RESULTS: Of the 200 children with CHI, 92 achieved spontaneous remission. The age of spontaneous remission was between one month and nine years, and 47 of the children were relieved before the age of one year. The median age of onset was 85 days (range: 1-2825 days) in the spontaneous remission group and 2 days (range: 1-210 days) in the nonspontaneous remission group (P < 0.05). The mean birth weight was 3.44 ± 0.76 kg for the spontaneous remission group and 3.95 ± 0.75 kg for the nonspontaneous remission group (P < 0.05). Of the 92 children in the spontaneous remission group, 65 were treated with diazoxide with effective rate of 81.5% (53/65). In 12 cases in which diazoxide treatment failed, octreotide was used with an effective rate of 83.3% (10/12). Of the 108 children in the nonspontaneous remission group, 88 were treated with diazoxide with an effective rate of 43.2 % (38/88), and 29 children were treated with octreotide with an effective rate of 48.28% (14/29). Of the 30 children in the spontaneous remission group that underwent mutation analysis of CHI-related pathogenic genes, 10 children (10/30, 33.3%) carried mutations. Of the 48 children in the nonspontaneous remission group that underwent mutation analysis of CHI-related pathogenic genes, 37 children (37/48, 77.1%) were found to carry mutations. All of the differences in the indices mentioned above were statistically significant. CONCLUSIONS: The rate of spontaneous remission of CHI was significantly higher in children with late age of CHI onset, light birth weight, effective diazoxide treatment, and no common pathogenic gene mutations. Spontaneous remission was also possible for a small number of children that carried mutations in the ABCC and KCNJ11 genes and in whom diazoxide treatment failed.

Morphometric measurement of lower lumbar intervertebral foramina based on digital three-dimensional simulation.

AIM: This study aimed to investigate the morphology of the lower lumbar intervertebral foramina through use of a digital three-dimensional (3D) simulation model to guide the endoscope through the intervertebral foramina. MATERIAL AND METHODS: Individuals without disease affecting the lumbar vertebrae underwent computed tomography (CT) scanning in the supine position. The CT images obtained were imported to medical software to reconstruct a 3D model of the lumbar vertebrae. The stereoscopic longitudinal and transverse diameters of the lumbar intervertebral foramina were measured directly on the established simulation model. Comparisons in terms of sex and age were performed using t-test or analysis of variance. RESULTS: In total, 100 individuals were included in the study. Average longitudinal and transverse diameters of the lower lumbar intervertebral foramen decreased moving inferiorly. The longitudinal and transverse diameters of the lower lumbar intervertebral foramina were similar between sexes and between age groups. However, longitudinal diameter decreased with age (P 0.05). CONCLUSION: The reconstructed lumbar vertebrae simulation model presented in this study has high fidelity to the structure of the human lumbar spine. This approach provides individualized, accurate, standardized, and detailed guidance for endoscopic surgery through the lumbar intervertebral foramen.

Novel Peroxides as Promising Anticancer Agents with Unexpected Depressed Antimalarial Activity.

Twenty six peroxides belonging to bridged 1,2,4,5-tetraoxanes, bridged 1,2,4-trioxolanes (ozonides), and tricyclic monoperoxides were evaluated for their in vitro antimalarial activity against Plasmodium falciparum (3D7) and for their cytotoxic activities against immortalized human normal fibroblast (CCD19Lu), liver (LO2 ), and lung (BEAS-2B) cell lines as well as human liver (HepG2) and lung (A549) cancer-cell lines. Synthetic ozonides were shown to have the highest cytotoxicity on HepG2 (IC50 =0.19-0.59 µm), and some of these compounds selectively targeted liver cancer (selectivity index values for compounds 13 a and 14 a are 20 and 28, respectively) at levels that, in some cases, were higher than those of paclitaxel, artemisinin, and artesunic acid. In contrast some ozonides showed only moderate antimalarial activity against the chloroquine-sensitive 3D7 strain of P. falciparum (IC50 from 2.76 to 24.2 µm; 12 b, IC50 =2.76 µm; 13 a, IC50 =20.14 µm; 14 a, IC50 =6.32 µm). These results suggest that these derivatives have divergent mechanisms of action against cancer cells and malaria-infected cells. A cyclic voltammetry study of the peroxides was performed, but most of the compounds did not show direct correlation in oxidative capacity-activity. Our findings offer a new source of antimalarial and anticancer agents through structural modification of peroxide compounds.

Impaired mitophagy in Fanconi anemia is dependent on mitochondrial fission.

Fanconi anemia (FA) is a rare genetic disorder associated with bone-marrow failure, genome instability and cancer predisposition. Recently, we and others have demonstrated dysfunctional mitochondria with morphological alterations in FA cells accompanied by high reactive oxygen species (ROS) levels. Mitochondrial morphology is regulated by continuous fusion and fission events and the misbalance between these two is often accompanied by autophagy. Here, we provide evidence of impaired autophagy in FA. We demonstrate that FA cells have increased number of autophagic (presumably mitophagic) events and accumulate dysfunctional mitochondria due to an impaired ability to degrade them. Moreover, mitochondrial fission accompanied by oxidative stress (OS) is a prerequisite condition for mitophagy in FA and blocking this pathway may release autophagic machinery to clear dysfunctional mitochondria.

Identification of differentially expressed genes that potentially confer pest resistance in transgenic ChIFN-γ tobacco.

Chicken interferon-γ (ChIFN-γ) is both an inhibitor of viral replication and a regulator of numerous immunological functions. However, since little is known about the mechanisms underlying the insect-resistance of transgenic ChIFN-γ, a transgenic ChIFN-γ tobacco line was employed in the present study to explore this mechanism. A cDNA microarray (with 43,760 unigenes) was used to analyze the gene expression profiles of transgenic and wild-type (WT) tobacco leaves at two different growth stages. Compared with the WT, 1529 and 405 expressed sequence tags were significantly up- or downregulated on days 119 and 147, respectively. The differentially expressed genes (DEGs) are involved in metabolic regulation, cell division and differentiation, material synthesis and transport, signal transduction, and protein synthesis and degradation. Candidate genes that may increase cell density, thicken cell walls, promote secondary metabolite synthesis, and mediate plant hormone-induced resistance responses were used to identify the ChIFN-γ-mediated insect-resistance mechanisms. The insect-resistance of transgenic ChIFN-γ tobacco possibly involves unknown signaling pathways, which may directly or indirectly affect DEG expression-mediating genes. The degree of pest resistance increased as the plants grew. Three genes likely to be related to jasmonic acid- or salicylic acid-dependent plant defense responses, including CAF 1, Cop 8/CSN, and HD, are implicated in the insect-resistance of the transgenic plants. The mechanism of transgenic ChIFN-γ tobacco resistance also involves RPS20 and other genes that induce microRNA-based gene regulation. The ChIFN-γ-mediated DGEs contribute to insect-resistance in transgenic ChIFN-γ tobacco, which provides new insight into the role of ChIFN-γ.

[ABCC8, KCNJ11 and GLUD1 gene mutation analysis in congenital hyperinsulinism pedigree].

OBJECTIVE: To explore the ABCC8, KCNJ11, and GLUD1 gene mutations of the 11 patients diagnosed as congenital hyperinsulinism (CHI). METHODS: A total of 11 CHI children hospitalized in Beijing Children's Hospital from November 2008 to February 2012 and their parents were chosen as the study subjects. Direct sequencing of PCR-DNA was used to analyze the 39 exons of ABCC8 gene, non-translational region and exon of KCNJ11 gene and 6, 7, 10, 11 and 12 exons of GLUD1 gene. RESULTS: An P629PfsX17 heterozygous mutation of ABCC8 gene was detected in case 1 and his father, an W288X heterozygous mutation of ABCC8 gene was detected in case 4 and his father, A640V and Q1196X mutations in ABCC8 gene in case 5 whose father only carried the Q1196X mutation. In case 6 and his father, an R269H mutation was found in GLUD1 gene. The genotype of 4 children's mothers was normal. No mutations were found in other 7 patients and their parents. CONCLUSIONS: The ABCC8 gene mutations are the main pathogenic mechanisms of Chinese children with CHI. In Chinese, P629PfsX17, W288X, A640V and Q1196X heterozygous mutation of ABCC8 gene and R269H heterozygous mutation of GLUD1 gene may lead to CHI. The inheritance mode of the mutations may be paternally or de novo.