[Diagnosis and treatment of new-onset or uncontrolled hyperthyroidism-induced liver injury].

The thyroid gland is the largest endocrine gland in the human body, which mainly secretes thyroid hormones. Thyroid hormone acts on almost all tissues and cells at different level regulating growth and development, metabolism and other functional activities of the body. Therefore, abnormal thyroid function can affect the multiple organs throughout the body. Liver, as the largest biochemical plant in the whole body, is widely regulated by thyroid hormones, and is one of the important target organs of the thyroid gland. Hyperthyroidism (HT for short) is a common disease of the endocrine system, which can cause liver injury, such as hepatomegaly, abnormal liver function, jaundice, cirrhosis, and liver failure. This phenomenon is also known as hyperthyroidism-induced liver injury, and it is more common in new or untreated or improperly treated patients with hyperthyroidism. The basic liver function test at the beginning of antithyroid drugs (ATD) treatment can clarify the degree of liver injury caused by hyperthyroidism itself, and further predict the additional liver injury with ATD therapy initiation. The core of treating hyperthyroidism-induced liver injury is to rapidly control hyperthyroidism, and restore normal liver function. This review briefly summarizes the incidence rate, possible mechanisms, pathological changes, clinical manifestations, laboratory, imaging and pathologic findings, and the recent advances in diagnosis and treatment of the hyperthyroidism-induced liver injury.

A two-year study of parental obesity status and childhood obesity in China.

BACKGROUND AND AIMS: We evaluated the association between parental obesity and their children's obesity parameters [e.g., percentage of body fat (PBF)] over time. METHODS AND RESULTS: The study included 2066 Chinese parents-children trios (n = 1001 girls and 1065 boys, aged 6-14 years). Children's height, weight, waist circumference (WC) and PBF (bioelectrical impedance analysis) were annually assessed from 2014 (baseline) to 2016. Information on parental height and body weight, and children's diet and physical activity was collected in 2014. The association between parental obesity and changes in their children's PBF during follow-up was analyzed using a mixed effects model. We also examined changes in children's BMI and WC in secondary analyses. Baseline mean BMI, WC, and PBF for children were 17.6 ± 3.5 kg/m2, 60.5 ± 9.6 cm, and 16.6 ± 6.5%, respectively. We observed that maternal, but not paternal, obesity was associated with a greater increase in children's PBF during the follow-up. An adjusted mean difference in annual increase of PBF was 0.41% [95% confidence interval (CI): 0.01%, 0.84%] for children with obese mothers, compared with those with normal-weight mothers. Both maternal and paternal obesity was associated with a greater increase in their children's BMI and WC (p trend<0.01 for both); however, the associations were stronger in mother-children pairs than those in father-children pairs. CONCLUSIONS: Maternal obesity was associated with a greater increase in PBF in Chinese school-aged children.

Body mass index, waist circumference, body fat mass, and risk of developing hypertension in normal-weight children and adolescents.

BACKGROUND AND AIMS: We prospectively examined the association between three adiposity indices, including body mass index (BMI), waist circumference (WC), and percentage of body fat (PBF), and risk of hypertension in normal-weight Chinese children. METHODS AND RESULTS: The current study included 1526 (713 boys and 813 girls) normal-weight Chinese children (age 6-14 years old), who were free of hypertension at baseline (2014). Heights, body weight, WC, and PBF (estimated by bioelectrical impedance analysis) were measured at the baseline. Blood pressure was repeatedly measured in 2014, 2015 and 2016. Hypertension was defined as either high systolic blood pressure and/or high diastolic blood pressure, according to age- and sex-specific 95th percentile for Chinese children. We used Cox proportional hazards model to calculate the association between exposures and hypertension. We identified 88 incident hypertension cases during two years of follow up. High BMI was associated with high risk of developing hypertension after adjusting for potential confounders. The adjusted hazard ratio for hypertension was 2.88 (95% CI: 1.24, 6.69) comparing two extreme BMI quartiles. Each SD increase of BMI (≈1.85 kg/m2) was associated with a 32% higher likelihood to developing hypertension (Hazard ratio = 1.32; 95% CI: 1.003, 1.73). In contrast, we did not find significant associations between WC or PBF and higher hypertension risk (p-trend >0.2 for both). CONCLUSION: High BMI, but not WC and PBF, was associated with high risk of hypertension in normal-weight Chinese children.

Association of PTPN22 gene polymorphism with type 1 diabetes mellitus in Chinese children and adolescents.

Previous studies have indicated that the protein tyrosine phosphatase nonreceptor type 22 gene (PTPN22) is associated with type 1 diabetes (T1DM) in the Caucasian population. In the present study, we investigated the relationship between PTPN22 genetic polymorphisms and T1DM in Chinese children. A total of 202 children and adolescents with T1DM and 240 healthy control subjects of Chinese Han origin were included in our analysis. Polymerase chain reaction-restriction fragment length polymorphism was used to determine the presence of the C1858T polymorphism in the PTPN22 gene. We found that the TT +TC genotype and the T allele of C1858T were more frequent in T1DM patients (19.40 and 10.0%, respectively) than in healthy subjects (7.51 and 4.0%, respectively), and the difference was significant (both P < 0.001). After adjusting for confounding variables such as gender, age, and family history of T1DM, the difference remained significant (P = 0.007, odds ratio = 2.88, 95% confidence interval 1.76-4.32). Our results indicate that genetic polymorphisms in the PTPN22 gene may increase the risk of T1DM in Chinese children and adolescents.

A comparison of patient knowledge of clinical trials and trialist priorities.

BACKGROUND: Recruitment to clinical trials remains poor, and patient knowledge of clinical trials is one barrier to recruitment. To identify knowledge deficits, we conducted and compared surveys measuring actual patient knowledge and clinical trialist priorities for patient knowledge. METHODS: Consenting patients at a tertiary cancer centre answered a survey that included 2 opinion questions about their own knowledge and willingness to join a trial, and22 knowledge questions. Clinical researchers at the centre were asked 13 questions about the importance of various trials factors. RESULTS: Of 126 patients surveyed, 16% had joined a clinical trial, and 42% had a secondary school education or less. The mean correct response rate on the knowledge questions was 58%. Higher rates of correct responses were associated with lower age (p = 0.05), greater education (p = 0.006), prior trial participation (p < 0.001), agreement or strong agreement with perceived understanding of trials (p < 0.001), and willingness to join a clinical trial (p = 0.002). Trialists valued an understanding of the rationale for clinical trials and of randomization, placebo, and patient protection, but those particular topics were poorly understood by patients. CONCLUSIONS: Patient knowledge about clinical trials is poor, including knowledge of several concepts ranked important by clinical trialists. The findings suggest that when developing education interventions, emphasis should be placed on the topics most directly related to patient care, and factors such as age and education level should be considered.

Ferroptosis in AS progression: role of miRNA.

We review the relationship between miRNAs associated with ferroptosis and the evolution of AS. Even though, more evidence is asked to determine the role of miRNAs associated with ferroptosis in the AS, this review will help us understand the role of miRNAs in ferroptosis and AS and may provide new insights for probing new biomarkers for the diagnosis and treatment of AS for the time to come. This is a narrative essay. Using PubMed as the main source, a literature search strategy was randomly implemented to index Scopus articles. No specific terminology is used. Studies have shown that ferroptosis plays a crucial role in the development of AS, and a large amount of ferroptosis in cells can lead to the progression of AS. MicroRNAs (MiRNAs) have been proved to be taken part in the biological course of ferroptosis and thus the process of AS is affected. The exact regulatory mechanism behind this appearance remains unclear. In order to clarify this, a growing number of studies have concentrated the regulatory role of miRNAs in the process of generation and development of ferroptosis, as well as the function of ferroptosis in the progression of AS. MiRNAs play a significant role in the process of ferroptosis and are incredibly significant in the occurrence, development, clinical diagnosis, treatment and prognosis evaluation of AS.

The Relationship between Body Mass Index and Incident Diabetes Mellitus in Chinese Aged Population: A Cohort Study.

OBJECTIVES: Previous studies reported that overweight older adults had a lower mortality after cardiovascular diseases attack, indicating being thinner might not always be better. However, there is an ongoing debate about what is the optimal range of body mass index (BMI) for the aged population. We aimed to evaluate the value of BMI for the prediction of incident diabetes mellitus (DM) in the Chinese elderly population. METHODS: A total number of 6,911 Chinese elderly people (4,110 men and 2,801 women, aged 71 ± 6.0 years) were included in this cohort study. BMI was measured at baseline (Jan 1, 2014, to Dec 31, 2014). All the participants were further classified into six groups: <18.5 kg/m2, 18.5 to <22.5 kg/m2, 22.5 to <25.0 kg/m2, 25.0 to <27.5 kg/m2, 27.5 to <30.0 kg/m2, and ≥30.0 kg/m2. Fasting blood glucose (FBG) and glycated hemoglobin A1c (HbA1c) were annually measured during follow-up (Jan 1, 2015-May 31, 2019). DM was confirmed if either FBG ≥ 7.0 mmol/L or HbA1c ≥ 6.5%. We used the Cox proportional hazard regression model to evaluate the association between BMI and the prediction of incident DM. RESULTS: Comparing individuals with a BMI range of 18.5 to <22.5 kg/m2 (reference), the hazard ratio for incident DM was 2.13 (95% CI: 1.54~2.95), 2.14 (95% CI: 1.53~3.00), 3.17 (95% CI: 2.19~4.59), 3.15 (95% CI: 1.94~5.09), and 3.14 (95% CI: 1.94~5.09) for the group with a BMI range of 22.5 to <25.0 kg/m2, 25.0 to <27.5 kg/m2, 27.5 to <30.0 kg/m2, and ≥30.0 kg/m2 after adjusting for baseline age, sex, blood pressure, lipid profiles, and eGFR (P trend < 0.001), after adjusting for the abovementioned confounders. The association tended to be closer in men and young participants, compared with their counterparts. CONCLUSIONS: High BMI was associated with a high risk of developing DM in the Chinese aged population. Thus, it is optimal for the aged population to maintain their body weight within a reasonable range to prevent chronic diseases.

Evaluation of serum makorin ring finger protein 3 (MKRN3) levels in girls with idiopathic central precocious puberty and premature thelarche.

This study aims to investigate serum makorin ring finger protein 3 (MKRN3) levels in girls with idiopathic central precocious puberty (ICPP) and premature thelarche (PT), in order to determine whether circulating MKRN3 level is associated with ICPP and PT. A total of 90 girls were enrolled in the stud. 30 age-matched girls were allocated for each group (ICPP, PT and healthy controls [HC], respectively). The base LH (B-LH) and E2 levels were higher in ICPP girls than those in HC and PT girls. The peak LH (P-LH) levels and P-LH/P-FSH values were obviously higher in ICPP girls than those in PT girls, while higher peak FSH (P-FSH) levels were detected in PT girls when compared to those in ICPP girls. Kisspeptin levels were lower in HC girls than those in ICPP and PT girls. MKRN3 levels were the highest in HC girls among the three groups. There were relatively strong negative correlations among MKRN3, kisspeptin and P-LH/P-FSH. Circulating MKRN3 can have an important role in the onset of ICPP and PT. However, this should not be used as an independent diagnostic criterion for diagnosing ICPP or differentiating ICPP from PT, but should be used only as an adjunctive diagnostic biomarker.

LncRNA CASC11 promotes the development of esophageal carcinoma by regulating KLF6.

OBJECTIVE: The aim of this study was to investigate the expression level of long non-coding RNA (lncRNA) CASC11 in esophageal carcinoma (ECa), and to further explore its relationship with clinical progression, pathological parameters, and prognosis of ECa patients. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine the level of lncRNA CASC11 in 45 pairs of ECa tissues and adjacent normal tissues. The relationship between the lncRNA CASC11 level and clinical progression, pathological parameters, and prognosis of ECa patients was analyzed. Meanwhile, the level of lncRNA CASC11 in the ECa cell lines was verified by qPCR as well. In addition, lncRNA CASC11 knockdown model was constructed using lentiviral transfection in ECa cell lines. Subsequently, the cell counting kit-8 (CCK8), colony formation assay, and flow cytometry were used to explore the effect of lncRNA CASC11 on the biological functions of the ECa cells. Finally, the Western Blot and the recovery experiments were used to explore the potential mechanism. RESULTS: In this work, the qPCR results showed that the expression level of lncRNA CASC11 in the ECa tissues was remarkably higher than that of the adjacent normal tissues, and the difference was statistically significant (p<0.05). Compared with patients with a low level of lncRNA CASC11, the pathological stage of patients with high expression was significantly higher, while the overall survival rate was lower (p<0.05). Compared with negative control (NC) group, the proliferation ability of the cells in the lncRNA CASC11 knockdown group CASC11 significantly decreased, whereas cell apoptosis remarkably increased (p<0.05). The Western Blot results revealed that protein expression of KLF6 was remarkably up-regulated after lncRNA CASC11 knockdown. In addition, the recovery experiments found that lncRNA CASC11 and KLF6 had mutual regulation, thereby promoting the malignant progression of ECa. CONCLUSIONS: LncRNA CASC11 expression was remarkably up-regulated in ECa, which was associated with the pathological stage and poor prognosis of ECa. In addition, lncRNA CASC11 could promote the malignant progression of ECa by mutual regulation of KLF6.

CD44 expression in human astrocytes and oligodendrocytes in culture.

CD44 is a glycoprotein present on the surface of some lymphocyte cell populations and other non-lymphoid cells, and is involved in many functions related to cell-cell and cell-matrix interactions. In this study, expression of CD44 antigen in primary neural cell cultures derived from fetal and adult human brains was investigated. In cultures processed for double immunofluorescence staining, approximately 80% of fetal astrocytes and more than 95% of adult astrocytes expressed the CD44 antigen on the cell bodies and processes; CD44 was also detected in 50-60% of adult oligodendrocytes. Neurons in fetal brain cell cultures did not express CD44 at all. Western blot analysis performed in astrocyte- and in neuron-enriched cultures confirmed the results from immunostaining and showed that the antibody against CD44 reacted with a polypeptide, of approximately 80 kD, that is present exclusively in the astrocyte-enriched cultures, but absent in neuron-enriched cultures. Our results indicate that CD44 glycoprotein is constitutively expressed in the human cells of glial cell lineage and its role is likely to be associated with normal neuroglia-mediated adhesion/recognition processes.

Co-expression of mRNA for neurotrophic factors in human neurons and glial cells in culture.

Enriched populations of neurons and astrocytes of 93-99% purity were obtained from mixed cultures of four human fetal brains. Total cellular RNA was extracted from cell pellets and reverse transcribed into cDNA. Five microliters of cDNA were subjected to PCR amplification using primers specific for sequences of NGF, BDNF, NT-3 and CNTF. PCR products were separated through 5% acrylamide gel and identified by DNA sequencing. Results showed that neurons expressed detectable levels of mRNA for NGF in all four cultures; BDNF and NT-3 mRNA was seen only in two cultures; CNTF mRNA was not detected in all four cultures. Astrocytes expressed mRNA for NGF, BDNF, and NT-3 but not for CNTF in all cultures examined. Astrocytic expression of mRNA for NGF, BDNF and NT-3 was found during the active cell proliferation as well as at a phase of mitotic quiescence. This study provides evidence that dissociated cell cultures of human neurons produce NGF, BDNF and NT-3 in early stages of their development and that astrocytes are constitutively committed to synthesize neurotrophic factors, NGF, BDNF and NT-3. The active synthesis of selected neurotrophic factors by neurons and astrocytes is relevant in supporting migration, survival and differentiation of developing neurons in vivo.

Peptidylglycine alpha-amidating monooxygenase (PAM) in Schwann cells and glia as well as neurons.

We raised an antiserum against the synthetic peptide FKETTRSFSNECLGTTR corresponding to the amino terminus of the enzyme peptidylglycine alpha-amidating monooxygenase (PAM). Control experiments were performed to determine the specificity of the antiserum and its suitability for the immunohistochemical identification of PAM-containing cells. An immunoaffinity column made with the antibody coupled to Sepharose permitted the isolation of the active enzyme. Peptide-agarose immunoadsorbant removed the antibodies responsible for the characteristic staining patterns in immunohistochemical experiments. As expected from the widespread distribution of amidated peptides in the nervous system, PAM immunoreactivity was detected in perikarya in a variety of locations, including the pituitary, the hypothalamic periventricular and supraoptic nuclei, neocortex, and sensory ganglia. Punctate immunostained fibers, especially around neuronal perikarya, were observed in regions known to receive amidated peptidergic afferents. In addition, PAM immunoreactivity was observed in some neurons not known to produce amidated peptides (e.g., pyramidal cells of the hippocampus). This result suggests that these neurons also produce an amidated peptide. PAM immunoreactivity was also detected in several unexpected cell types, including ependyma, choroid plexus, oligodendroglia, and Schwann cells. The presence of enzymatically active PAM in Schwann cells was confirmed by measurements of amidating activity in ligated and control sciatic nerve. These results suggest that these non-neuronal cells may produce amidated peptides.

Identification of a novel protein (G210) specific to the Golgi apparatus.

A monoclonal antibody, 3C9, has enabled the detection of a novel Golgi-specific protein in bovine tissues. Immunohistochemical studies at the light microscopic level have detected the 3C9 antigen only in certain cells: exocrine pancreas, gut epithelium, and thymus epithelium. Examination of gut and pancreas by immunoelectron microscopy showed a localization exclusive to the Golgi apparatus. The relative molecular weight of the antigen detected by immunoblotting is 210,000 daltons. The antigen is not extracted from microsomal membranes of bovine gut epithelium by sodium carbonate solutions. Furthermore, the 3C9 antigen enters into the detergent phase when Triton X-114 partitioning methods are used. These data strongly suggest that this novel antigen is an intrinsic membrane protein, resident in the Golgi apparatus of certain cells. Moreover, they enhance the hypothesis that the distribution of enzymes and polypeptides in the Golgi apparatus is cell specific.

Spermicidal effect in vitro by the active principle of garlic.

The in vitro spermicidal effect of Allitridum, an active principle of garlic, was investigated. The data showed that sperm motility was inhibited with various concentrations of Allitridum at different intervals ranging from 20 seconds-200 minutes as compared to control. An obvious immobilization of spermatozoa occurred at 7.5 mg/ml of Allitridum. The effects on sperm motility appeared to be dose-dependent.

PIP: The in vitro spermicidal effect of Allitridum, an active principle of garlic, was investigated. The data showed that sperm motility was inhibited with various concentrations of Allitridum at different intervals ranging from 20 seconds-200 minutes as compared to control. An obvious immobilization of spermatozoa occurred at 7.5 mg/ml of Allitridum. The effects on sperm motility appeared to be dose-dependent. Male rats and hamsters were used for the study as well as human spermatozoa.

Inhibition of glial cell line-derived neurotrophic factor induced intracellular activity by K-252b on dopaminergic neurons.

The c-ret protooncogene encodes Ret, the functional tyrosine kinase receptor for glial cell line-derived neurotrophic factor (GDNF). K-252b, a known protein tyrosine kinase inhibitor, has been shown earlier to inhibit the trophic activity of brain-derived neurotrophic factor on dopaminergic (DAergic) neurons and nerve growth factor on basal forebrain cholinergic neurons while potentiating neurotrophin-3 activity on central cholinergic and peripheral sensory neurons and PC12 cells. We tested whether K-252b would modulate GDNF-induced differentiation in DAergic neuron cultures. Exposure to 1 ng/ml GDNF increased dopamine (DA) uptake 80% above control, whereas treatment with 5 microM K-252b decreased the efficacy of GDNF by 60%. Concentrations of GDNF of <100 pg/ml were completely inhibited, whereas concentrations of >100 pg/ml were moderately active, between 10 and 20% above control. In addition, K-252b shifted the ED50 from 20 to 200 pg/ml. GDNF treatment increased soma size and neurite outgrowth in tyrosine hydroxylase-immunoreactive neurons. K-252b inhibited differentiation of these morphological parameters induced by GDNF. Furthermore, GDNF stimulated Ret autophosphorylation at maximal levels, whereas the inhibition of DA uptake and morphological differentiation by K-252b correlated with a significantly decreased level of Ret autophosphorylation. Therefore, K-252b is able to inhibit intracellular activities induced by GDNF on mesencephalic DAergic neurons.

Expression and distribution of GAP-43 in human astrocytes in culture.

By combining mRNA analysis and immunocytochemistry, we investigated the expression of the growth associated protein 43 (GAP-43) in enriched populations of astrocytes, obtained from mixed cultures of human fetal brains. Total cellular RNA was extracted from cell pellets and reverse transcribed into cDNA; cDNA was subjected to PCR amplification using primers specific for GAP-43 and PCR products were separated through polyacrylamide gels. Double immunofluorescence staining was performed on dissociated cell cultures using antibodies to glial fibrillary acidic protein (GFAP) and to GAP-43. Results showed that both transcription and translation for GAP-43 occur in cultured astrocytes. GAP-43 immunoreacting material was detected in the cell processes and diffusely in the cytoplasm of GFAP-positive astrocytes, during early stages of maintenance in vitro. In older cultures, GAP-43 immunoreactivity persisted in a large percentage of cells, with a tendency to accumulate in perinuclear areas. These observations provide evidence that GAP-43 is not restricted to neuronal cells. The close spatial association with cytoskeletal constituents, as observed in astrocytes, suggests a role for this protein in the control of cell shape, motility and adhesion processes.

Inhibition of phosphatidylinositol 3-kinase activity blocks cellular differentiation mediated by glial cell line-derived neurotrophic factor in dopaminergic neurons.

Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for midbrain dopaminergic neurons. To begin to understand the intracellular signaling pathways used by GDNF, we investigated the role of phosphatidylinositol 3-kinase activity in GDNF-stimulated cellular function and differentiation of dopaminergic neurons. We found that treatment of dopaminergic neuron cultures with 10 ng/ml GDNF induced maximal levels of Ret phosphorylation and produced a profound increase in phosphatidylinositol 3-kinase activity, as measured by western blot analysis and lipid kinase assays. Treatment with 1 microM 2-(4-morpholinyl)-8-phenylchromone (LY294002) or 100 nM wortmannin, two distinct and potent inhibitors of phosphatidylinositol 3-kinase activity, completely inhibited GDNF-induced phosphatidylinositol 3-kinase activation, but did not affect Ret phosphorylation. Furthermore, we examined specific biological functions of dopaminergic neurons: dopamine uptake activity and morphological differentiation of tyrosine hydroxylase-immunoreactive neurons. GDNF significantly increased dopamine uptake activity and promoted robust morphological differentiation. Treatment with LY294002 completely abolished the GDNF-induced increases of dopamine uptake and morphological differentiation of tyrosine hydroxylase-immunoreactive neurons. Our findings show that GDNF-induced differentiation of dopaminergic neurons requires phosphatidylinositol 3-kinase activation.

Midkine is a mediator of retinoic acid induced neuronal differentiation of embryonal carcinoma cells.

Midkine (MK) is a novel growth factor and is the product of a retinoic acid responsive gene. When P19 murine embryonal carcinoma (EC) cells were exposed to MK, they differentiated into neurons, and the neuronal differentiation was accompanied by expression of choline acetyltransferase activity. Synthesis and release of MK in the EC cells treated with retinoic acid were shown by Western blot analysis, and rabbit anti-MK antibody attenuated the action of retinoic acid to induce the neuronal differentiation. These results indicate that MK is one of the mediators of retinoic acid action to induce the neuronal differentiation in EC cells.

[Antifertility effects of RU-486 in combination with anordrin in rats].

RU-486 and anordrin suspended or dissolved in tea seed oil, alone or in combination, were given orally to rats on d 6-8 or d 11-13 of pregnancy, respectively. Complete interruption of early pregnancy was obtained after RU-486 at 8 mg/kg alone or 2.5 mg/kg combined with anordrin 2 mg/kg when given on d 6-8 of pregnancy. A complete mid-trimester abortion was obtained after RU-486 10 mg/kg alone or 4 mg/kg combined with anordrin 3 mg/kg when given on d 11-13 of pregnancy. Results obtained from the endometrial transformation test, the uteri cytoplasmic progesterone receptor estimation in immature rabbits, the deciduoma-inhibited test in pseudopregnant rats and the serum progesterone level in pregnant rats showed that RU-486 in combination with anordrin did not possess progestational, but rather marked antiprogestational activities. Since anordrin is relatively easy to obtain in China, RU-486 combined with anordrin may be ready to be used clinically as an effective oral antifertility agent.