The effect of levetiracetam and oxcarbazepine monotherapy on thyroid hormones and bone metabolism in children with epilepsy: A prospective study.

BACKGROUND: Long-term treatment with certain antiepileptic drugs may lead to thyroid function disturbances or alterations in bone metabolism; the data on the effects of new antiepileptic drugs on this are limited and conflicting, especially in children with epilepsy. Therefore, the aim of this study was to investigate the effects of levetiracetam and oxcarbazepine on thyroid hormone levels and bone metabolism in children with epilepsy. METHODS: A total of 51 children with new-onset partial epilepsy were selected. They were randomly treated with either levetiracetam (n = 25), or oxcarbazepine (n = 26) monotherapy. Eight of the 51 patients were excluded for failing to take the drug continuously or failing to undergo a regular review. Thus, 43 patients were finally included (levetiracetam: 23 patients, oxcarbazepine: 20 patients). A control group consisting of age- and sex-matched healthy subjects (n = 20) was included for comparison. Serum triiodothyronine, tetraiodothyronine, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, calcium, phosphorus, alkaline phosphatase, osteocalcin, parathyroid hormone, and 25-hydroxyvitamin D levels and bone mineral density values were measured before and at 6 and 12 months after therapy in all groups. RESULTS: At baseline, thyroid hormone levels, bone metabolism index, and bone mineral density values did not differ between the control group and the drug-treated groups. Levetiracetam-treated patients showed no significant changes in thyroid hormone levels, bone metabolism, and bone mineral density during the 12-month follow-up period compared with baseline values. In the oxcarbazepine group, compared to baseline values, serum free thyroxine levels decreased after 12 months of treatment (Z = -3.115, p = 0.002), and after 6 and 12 months of treatment, calcium levels decreased (Z = -3.705, p < 0.001 and Z = -3.884, p < 0.001, respectively) and parathyroid hormone levels increased (Z = -3.698, p < 0.001 and Z = -3.921, p < 0.001, respectively); however, all other parameters did not differ from baseline values. CONCLUSION: Our data show that levetiracetam treatment has no significant effect on thyroid function and bone metabolism in children with epilepsy. Long-term use of oxcarbazepine may reduce serum free thyroxine levels, resulting in impaired thyroid function, and may reduce serum calcium and increase parathyroid hormone levels, leading to bone metabolism disorders.

[Change of Hepcidin in Patients with Iron Overload at the Tibet Plateau].

OBJECTIVE: To explore the possible etiological factors of iron overload through detecting plasma hepcidin level of adult males at Tibet plateau. METHODS: 81 Tibetan male adult patients hospitalized in our department during January 2017 - December 2018 were selected, and divided into iron overload group and non-iron overload group. The difference in serum ferritin, serum iron, total iron binding capacity, hemoglobin, HBSAg, ALT, AST, albumin, creatinine and hepcidin of patients in each group were tested. To analyze the differences between groups. The regression analysis was applied to analyze the relationship between laboratory index and hepcidin. RESULTS: The plasma hepcidin of iron overload group was significantly higher than that of the non-iron overload group [93.69 (65.57-133.92) ng/ml vs 63.93 (40.01-90.65) ng/ml] (P=0.005). And there was a positive correlation between plasma hepcidin and ferritin (ß=0.03 ng/ml，95%CI 0.01-0.05) (P<0.01) and BMI (ß=5.71 ng/ml，95%CI 0.54-10.88) (P<0.05）. CONCLUSION: Iron overload at Tibet plateau can not be attributed to hepcidin deficiency in Tibetan adult male patients. Iron metabolism disorders in Tibetan population may be associated with metabolic syndrome.

Serum Ferritin Independently Predicts the Incidence of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

AIM: This study aimed to determine whether serum ferritin (SF) is an independent risk factor of the incidence of chronic kidney disease (CKD) and rapid renal function decline (RFD) in male Tibetan patients with type 2 diabetes mellitus (T2DM). METHODS: We performed a retrospective cohort study that included 191 male Tibetan patients with T2DM without CKD. Patients were divided into three groups according to the level of SF. The following outcomes were measured: cumulative incidence of chronic kidney disease [i.e. estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 and/or urinary albumin/creatine ratio (ACR) ≥30 mg/g] and RFD (i.e. decrease in eGFR of ≥25% from baseline or a decline rate of ≥3 mL/min per 1.73 m2 annually). RESULTS: In total, over a median follow-up period of 23 months, 30 (15.7%) and 89 patients (46.6%) developed CKD and RFD. In multivariable Cox models, a 100 ng/mL increment in SF was associated with a 1.12-fold (95% CI: 1.02-1.24) higher adjusted risk for incidence of CKD. The adjusted-HR of CKD was 1.31 (95% CI: 0.38-4.53) and 2.92 (95% CI: 0.87-9.77) for those in tertile 2 and tertile 3, respectively, compared with the patients in tertile 1. However, SF was not significantly associated with RFD (adjusted-HR: 1.06, 95% CI: 0.99-1.14). CONCLUSION: Serum ferritin independently predicts the incidence of CKD in male Tibetan patients with T2DM. High levels of serum ferritin may play a role in the pathogenesis leading to the development of CKD in T2DM.

[Analysis of HFE and Non-HFE Mutations in a Tibet Cohort with Iron Overload].

OBJECTIVE: The explore the molecular basis of iron-overload in Tibet nationality population of Tibet. METHODS: The inpatients with iron-overload in our department from Dec. 1st 2014 to Jul.31st 2016 were enrolled in this study. Abdominal MRI and the mutation sites C282Y and H63D in HFE exon were examined. For HFE mutation-negative patients, the non-HFE mutation was detected, including 5 HJV mutations of G320V, p.Q312X, p.D249H, p.I281T, p.C321X and 2 TFR2 mutations: (Y250X, I238M), and 2 SLC40A1 mutations: (V162del, N144H). RESULTS: Among 113 iron overload patients, only one showed homozygous p.H63D mutation, and one showed heterozygosis p.H63D mutation. In 73 patients accepted non-HFE gene detection, only one was heterozygosis p.D249N mutation in HJV, and one was heterozygosis p.I238M mutation in TFR2. CONCLUSION: Currently, the pathogenic gene for Tibetan iron-overload has not yet been found.

Analysis of genomic variation in lung adenocarcinoma patients revealed the critical role of PI3K complex.

BACKGROUND: Molecularly targeted therapies improved survival status of some patients with lung adenocarcinoma, which accounts for 40% of all lung cancers, and in-depth study of gene alterations is important for the personalized treatment. METHODS: The legacy archive data of clinical information and genomic variations under the project TCGA Lung Adenocarcinoma were downloaded from the GDC Data Portal using R package TCGAbiolinks. The significantly aberrant copy number variants segments were figured out using GAIA. After annotation, the genes involving CNV were used to get enriched pathways. Recurrent amplifications and deletions were identified and visualized by OncoPrint. Genomic alterations in cancer, including CNV and mutations, were represented in Circos. RESULTS: The significantly aberrant CNV segments were found, and the genes involved were associated with the immune system. In an analysis of 517 mutation annotated files, we highlighted 63 highly recurrent mutated genes which were associated with lung cancer signaling. These genes involved in important pathways related to cancer progression. The intersections between the genes involving in the significantly aberrant CNV and the genes harboring recurrent somatic SNP were extracted. The PI3K protein family acted as critical roles in the lung adenocarcinoma, since the components of the PI3K protein family include PIK3C2B, PIK3CA, PIK3R1 and so forth were presented in the intersections. CONCLUSION: We represented a comprehensive annotation of genomic alterations in lung adenocarcinoma and proposed that PI3K signaling proteins were critical for it.

Neurotoxicity of prenatal alcohol exposure on medullary pre-Bötzinger complex neurons in neonatal rats.

Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor (5-HT2AR) is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10% (v/v) throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2AR protein and mRNA levels in the pre-Bötzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2AR protein and mRNA levels.

[Effect of prenatal alcohol exposure on rhythmic respiratory discharge activity in medullary slices of neonatal rats].

OBJECTIVE: To investigate the effects of prenatal alcohol exposure on rhythmic respiratory discharge activity (RRDA) in the medullary slices of neonatal rats. METHODS: Ten pregnant female SD rats were exposed to 0, 4%, 6%, 8%, and 10% alcohol in drinking water from 1 week before till 3 days after delivery. The medullary slices of the neonatal rats containing the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets were prepared and perfused with modified Kreb's solution to record RRDA from the hypoglossal nerve rootlets using suction electrodes. RESULTS: No significant difference was found in RRDA in 50 min among the neonatal rats with prenatal exposure to 0, 4%, 6%, and 8% alcohol, but the RRDA in 10% alcohol exposure group became irregular. Prenatal exposure to increased alcohol concentrations caused attenuated RRDA attenuated in the neonatal rats, shown by shortened inspiratory time (TI), decreased respiratory frequency (RF), and reduced integral amplitude (IA) as compared with those in the control group. CONCLUSION: Prenatal alcohol exposure inhibits RRDA in medullary slices of neonatal rats, which might be a mechanism by which maternal alcohol exposure causes suppressed offspring respiratory functions.

[Electronic regulation mode on implantable medical device].

OBJECTIVE: To discuss the methods of implantable medical device supervision reform. METHODS: Methods of literature review, comparative study, the research of situation, developmental study and case study were adopted. RESULTS: It is the untrue and asymmetric information of implantable medical device that results in improper behavior in the implantable medical device industry. CONCLUSIONS: A implantable medical device electronic monitoring system, namely establishing the independent but interrelated real-time dynamic updating of the databases, which would guarantee the information of implantable medical device is open and transparent, eliminate false food information transmission, vindicate the good order of domestic implantable medical device industry and protect the vital interests of the public.

[The effect of metformin on insulin receptor protein tyrosine kinase activity of HIT-T15 cell exposed to high concentration glucose and free fatty acid].

OBJECTIVE: To study the effect of metformin on insulin receptor (IRc) protein tyrosine kinase (PTK) activity of HIT-T15 cell exposed to high glucose and free fatty acid (FFA) concentration, and to explore the mechanism of metformin (MF) improving beta cell insulin resistance. METHODS: HIT-T15 cells were incubated for 48 h in a medium containing 5.5-16.7 mmol/L glucose and 0.5 mmol/L palmitic acid respectively. The cells were re-incubated for another 24 h with or without 2.5 microg/mL MF. The PTK activities of IRc were measured by radioactive enzyme assay. RESULTS: The enzymatic activities of IRc PTK were significantly decreased to HIT-T15 cells having the exposure to high glucose or high FFA concentration, when compared to control [(52.5 +/- 18.6) or (54.6 +/- 14.0) vs. (119.4 +/- 29.1) pmol/(min x microg), P < 0.01 respectively. The enzymatic activities of IRc PTK in HIT-T15 cells reincubated with 2.5 microg/mL MF for an additional 24 h were significantly increased vs MF free group [(113.0 +/- 29.8) vs. (52.5 +/- 18.6) pmol/(min x microg), x 98.6 +/- 26.1) vs. (54.6 +/- 14.0) pmol/(min x microg), P < 0.01 respectively], and were no significant difference in comparison with control group (P > 0.05). CONCLUSION: The enzymatic activities of IRc PTK are significantly decreased in HIT-T15 cells chronically exposed to elevated glucose or free fatty acids levels. Metformin can restore approximately normal enzymatic activities of PTK of HIT-T15 cells, of which the PTK activities have been impaired by chronic exposure to high glucose or free fatty acids levels.

[A study on the mechanism of islet cell insulin resistance in high-fat-diet obese rats].

OBJECTIVE: To study the changes of insulin signal transduction in islet cells of high-fat-diet rats with peripheral insulin resistance (IR). METHODS: Thirty male Wistar rats were randomly divided into 2 equal groups: high-fat-diet group and control group to be fed with high-fat food and normal food respectively. Twenty weeks after the rats were sacrificed. The contents of insulin and glucagon in homogenate of pancreas were detected during islet cell perifusion, and insulin receptor (IRc) and insulin receptor substrates (IRS-1 and IRS-2) were detected by immunohistochemistry. RESULTS: (1) The insulin sensitive index (ISI) was significantly decreased in the high-fat-diet rats in comparison with the normal rats, while the contents of glucagon in blood and in homogenate of pancreas were both significantly increased in the high-fat-diet rats (362 pg/ml +/- 58 pg/ml vs 291 pg/ml +/- 35 pg/ml; 442 pg/ml +/- 56 pg/ml vs 287 pg/ml +/- 48 pg/ml, both P < 0.05). (2) The glucose stimulated insulin secretion (GSIS) was impaired in the high-fat-diet rats. 16.7 nmol/L glucose could inhibit the glucagon secretion by the alpha cells of the normal rats, but not of the high-fat-diet rats. (3) The expression of IRc, IRS-1 and IRS-2 in islets was stronger in the peripheral cells (non-insulin secretion cells) than in the center cells (insulin secretion cells). The expression of IRc and IRS-2 was significantly decreased by 28% and 22% respectively in the high-fat-diet rats compared with the normal controls (both P < 0.01). CONCLUSION: High-fat-diet rats have impairment of insulin signal transduction in islet cells, which may contribute to the insulin resistance of islet alpha and beta cells and explain, at least in part, the dysfunction of the islet cells under peripheral IR.

[Effects of Anxin Granules on blood lipid and ultrastructure of aorta in rabbits with dyslipidemia].

OBJECTIVE: To study the effects of Anxin Granules on dyslipidemia in rabbits caused by high fat plus high cholesterol diet. METHODS: Thirty-two healthy New Zealand male white rabbits were randomly divided into 4 groups: normal control group, untreated group, Zhibituo Tablet-treated group and Anxin Granule-treated group. Rabbits in the normal control group were fed with regular chow, while rabbits in the other three groups were fed with high fat plus high cholesterol diet. Zhibituo Tablets and Anxin Granules were administered to the rabbits in Zhibituo Tablet-treated group and Anxin Granule-treated group at a daily oral dose respectively. At the end of the 10th week, the levels of serum total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A(1) (ApoA1) and apolipoprotein B (ApoB) were tested in each group, and the ultrastructures of the aorta were also observed by an electron microscope. RESULTS: Anxin Granules could reduce the levels of TC, TG, LDL-C and ApoB. The results observed by electron microscope showed that, as compared with the untreated group and the Zhibituo Tablet-treated group, the atherosclerosis of aorta in the Anxin Granule-treated group was lighter. And it was found that there were few lipid droplet vacuoles in cytoplasm of the endothelial cells, and various cell organs and elastic membrane were existed, but no lipid droplet vacuoles in cytoplasm of the medial smooth muscle cells. CONCLUSION: Anxin Granules can regulate the metabolism of blood lipid and inhibit the formation of atherosclerosis caused by hyperlipidemia in rabbits.