Ectopic parathyroid adenomas (PAs) can occur in numerous locations and are thought to be the cause of a significant portion of failed primary surgery for hyperparathyroidism. PA is a rare cause of hoarseness, which may be harbingers of a malignant process. Here, we describe an unusual case of an ectopic PA in the carotid sheath presenting as unilateral vocal cord paralysis (VCP). A 49-year-old lady presented with a 1-week history of hoarseness, irritating cough and shortness of breath. Fibreoptic laryngoscopy revealed left VCP. Ultrasound and computed tomography of the neck demonstrated a mass in the carotid sheath. Laboratory investigations revealed hypercalcemia (3.10 mmol/L), hypophosphatemia (0.81 mmol/L) and elevated intact parathyroid hormone OPTED level (381.6 pg/mL), despite of a negative Tc-99m-sestamibi scan. After more rigorous tests, the ectopic tumor adjacent to the left vagus nerve was successfully resected, with subsequent histopathological confirmation of PA. The patient eventually got a normal iPTH level and serum calcium postoperatively, and regular voice function was also regained 4 months after surgery. This case emphasizes the importance of broad differential diagnosis and thorough workup. Although most patients with PA present with hypercalcemia, this disease entity also need to be considered in the differentials of neck masses and VCP.
Thyroglobulin measurement in the needle washout after fine-needle aspiration (FNA-Tg) served as an important measurement for suspicious recurrent or metastatic lesions. We conducted a pooled analysis to evaluate the diagnostic accuracy of FNA-Tg and searched electronic databases for original articles in English from 1993 through 2017. Finally, a total of 22 studies containing 2,670 lymph nodes (LNs) that enrolled participants with suspicious neck LNs during thyroid nodule vorkup or papillary thyroid cancer (PTC) follow-up were included. In our analysis, the overall pooled sensitivity for FNA-Tg was 0.91 (95%CI: 0.87-0.93), specificity was 0.94 (95% CI: 0.91-0.96). Meta regression revealed that the cutoff value and status of serum Tg were sources of heterogeneity for sensitivity, and the cutoff value was source of heterogeneity for specificity. Additionally, the cutoff value and status of serum Tg were sources of heterogeneity in the joint model. Subgroup analysis about cut-off value showed that the choice of 1 ng/mL had highest sensitivity, 40 ng/mL had highest specificity. At last, we arrived at the conclusion that FNA-Tg measurement had high specificity and sensitivity in the early detection of LNs metastases from PTC by our meta-analysis. The technique was simple and could be recommended to apply in any FNA facility, especially when LN were small-sized. Significantly, a better standardization of criteria for FNA-Tg detection and cutoff value was required to provide useful data and to improve management of PTC patients in the future.
Autoimmune thyroid disease (AITD) is characterized by a loss of self-tolerance to thyroid antigen. Tregs, whose proportions are controversial among CD4+ T cell from AITD patients (AITDs), are crucial in immune tolerance. Considering that drugs might affect Treg levels, we assumed that the differences originated from different treatment statuses. Thus, we performed a meta-analysis to explore proportions of Tregs in untreated and treated AITDs. PubMed, Embase and ISI Web of Knowledge were searched for relevant studies. Review Manager 5.3 and Stata 14.0 were used to conduct the meta-analysis. Subgroup analysis based on different diseases and cell surface markers was performed. Egger linear regression analysis was used to assess publication bias. Approximately 1,100 AITDs and healthy controls (HCs) from fourteen studies were included. Proportions of Tregs among CD4+ T cells of untreated AITDs were significantly lower than those in HCs (p = 0.002), but were not in treated patients (p = 0.40). Subgroup analysis revealed lower proportions of Tregs in untreated Graves' disease patients (GDs) (p = 0.001) but did not show obvious differences in untreated Hashimoto's thyroiditis patients (ITTs) (p = 0.62). Furthermore, proportions of circulating FoxP3+ Tregs were reduced in untreated GDs (p < 0.00001) and FITs (p = 0.04). No publication bias was found. In this first meta-analysis exploring proportions of circulating Tregs among CD4+ T cells of AITDs with different treatment statuses, we found that Tregs potentially contribute to the pathogenesis of MID but function differently in GD and LIT. Remarkably, FoxP3+ Tregs, which were decreased in both diseases, might be promising targets for novel therapies.
Little is known about the association between equol and bioavailable testosterone (BT) in adults. In this study, we examined the associations of urinary equol concentrations with serum concentrations of total, bioavailable and free testosterone (FT), dehydmepiandrostemne sulfide (DHEAS), free androgen index (FAT) and sex hormone-binding globulin (SHBG). This cross-sectional study included 1,904 women with a mean age of 59.7 years. Urinary equol concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The serum androgenic indices and SHBG were also determined. Overall, urinary equol tended to be inversely associated with bioactive forms of androgenic indices (BT, FT or FAI) but not with total testosterone (TT) or DHEAS. Urinary equol was also positively associated with SHBG. In multi-covariate-adjusted analyses stratified by menopausal status, graded and inverse associations between urinary equol and bioactive forms of androgenic indices (BT, FT and FAI) were observed in postmenopausal women (all p-trends < 0.05), but not in premenopausal women. A significant positive association between urinary equol and SHBG was observed only in postmenopausal women. No significant associations were observed between urinary equol and TT or DHEAS in either group. A path analysis indicated that these associations of equol with androgens in postmenopausal women might be mediated by SHBG. In conclusion, urinary equol exhibited graded and inverse associations with BT or FT, but not TT in women. However, further longitudinal studies of human patients are needed to confirm these results and overcome the limitations of cross-sectional studies.
Polycystic ovary syndrome (PCOS) diagnosis combines various clinical phenotypes. The definition of PCOS is still controversial because insulin resistance (IR) and dysmetabolism do not constitute PCOS diagnostic criteria. We analyzed whether a circulating biomarker zinc-alpha 2-glycoprotein (ZAG) related to IR and metabolic dysfunction can predict PCOS phenotypes. We then recruited 100 PCOS patients and 99 healthy women as the control group to assess the relationship between ZAG and metabolic characteristics. The euglycemic-hyperinsulinemic clamp helped assess insulin sensitivity, and the enzyme immunometric assay was deployed for ZAG levels. Our PCOS cohort presented sixty-nine patients with hyperandrogenism, eighty-six patients with chronic oligoanovulation, and eighty-one patients with polycystic ovaries by ultrasonographic evaluation. Additionally, the circulating ZAG levels were considerably reduced in all PCOS patients compared with healthy women (p < 0.05 or p < 0.01). Additionally, sixty-nine PCOS patients had IR, and circulating ZAG levels were also different among the phenotypes. Furthermore, the nonnoandrogenic type specifically exhibited the highest circulating ZAG levels among all PCOS phenotypes (p < 0.05 or p < 0.01). Additionally, nonnoandrogenic phenotype patients had reduced HOMA-IR scores and greater M-values than those in the classic phenotypes (p < 0.05). The circulating ZAG levels, however, were not associated with oligoanovulation but were correlated with hyperandrogenism and PCO morphology. In summary, circulating ZAG levels serve as suitable PCOS phenotype biomarkers, aiding physicians to identify women who merit screening.
The efficacy of liraglutide in the treatment of glycemic variability in type 2 diabetic patients remains to be fully elucidated. Some studies evaluated the efficacy and safety of liraglutide in glycemic variability, and this meta-analysis was performed to evaluate the accuracy of the results of existing studies on the efficacy of liraglutide. We conducted a comprehensive search for all relevant studies published in PubMed, EMBASE, Cochrane Library, and China Academic Journal Full-Text Database from the beginning of 2011 to October 31, 2019. The mean +/- SD and 95% confidence interval were used for evaluation, and subgroup and sensitivity analysis were carried out. Publication bias was estimated by funnel plots and Egger's tests. A total of 16 studies were included in the meta-analysis involving 492 participants. MAGE (mean amplitude of glycemic excursion), LAGE (largest amplitude of glycemic excursions), SD (standard deviation of blood glucose), and MODD (mean of daily differences) were collected to reflect the variability of blood glucose. The glycemic variability indexes of patients before and after treatment with liraglutide were compared. Patients with treatment had lower glycemic variability compared with patients receiving treatment of liraglutide. Compared with the patients before the treatment, the patients after the treatment had a smaller glycemic variability (MAGE: I-2 = 92%, p < 0.01, Z = 11.91, p < 0.01, MD = -2.78, 95%CI: -3.24 - -2.32; LAGE: I-2 = 76%, p = 0.08, Z = 9.94, p < 0.01, MD = -2.20, 95%CI: -2.59 - -1.81; MODD: I-2 = 74%, p = 0.002, Z = 14.03, p < 0.01, MD = -0.90, 95%CI: -1.02 - -0.77; SD: I-2 = 93%, p < 0.01, Z = 3.62, p < 0.01, SMD = -1.77, 95%CI: -2.73 - -0.81). Sensitivity analysis showed that our results were reliable and no evidence of significant publication bias was detected. The results of this study suggest that patients with type 2 diabetes treated with liraglutide are associated with lower glycemic variability.
It has been shown that circular RNAs, a class of non-coding RNA molecules, play an important role in the regulation of glucose and lipid homeostasis. In the present study, we sought to investigate the function of circular RNA HIPK3 (circHIPK3) in diabetes-associated metabolic disorders, including hyperglycemia and insulin resistance. Results show that oleate stimulated circHIPK3 increase, and that circHIPK3 enhanced the stimulatory effect of oleate on adipose deposition, triglyceride (TG) content, and cellular glucose content in HepG2 cells. MiR-192-5p was the potential target of circHIPK3, since circHIPK3 significantly decreased miR-192-5p mRNA level, whereas anti-circHIPK3 significantly increased miR-192-5p mRNA level. Further study shows that transcription factor forkhead box O1 (FOXO1) was a downstream regulator of miR-192-5p, since miR-192-5p significantly decreased FOXO1 expression, whereas circHIPK3 significantly increased FOXO1 expression. Notably, the inhibitory effect of miR-192-5p was significantly reversed by circHIPK3. In vivo study shows that anti-miR-192-5p significantly increased blood glucose content, which was significantly inhibited by FOXO1 shRNA. MiR-192-5p significantly decreased adipose deposition and TG content in HepG2 cells, which was significantly reversed by the co-treatment with circHIPK3. Forskolin/dexamethasone (FSK/DEX) significantly increased cellular glucose, mRNA level of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), and this stimulatory effect of FSK/DEX was significantly inhibited by miR-192-5p. In the presence of circHIPK3, however, the inhibitory effect of miR-192-5p was totally lost. In summary, the present study demonstrated that circHIPK3 contributes to hyperglycemia and insulin resistance by sponging miR-192-5p and up-regulating FOXO1.
Primary contents of dietary fat are three or four types of fatty acids, namely saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n6-polyunsaturated fatty acid (n6PUFA) and, to less extent, n3-polyunsaturated fatty acid (n3PUFA). Previous studies suggest that increased SFA, MUFA, and n6PUFA in high fat diets (HFDs) stimulate the origination, growth, and liver metastasis of pancreatic cancer cells, whereas increased n3PUFA has the opposite effects. It is unclear whether the fatty acid-induced effects are based on changed fatty-acid composition of involved cells. Here, we investigated whether increased SFA, MUFA, n6PUFA, and n3PUFA in different HFDs determine the FA profiles of pancreatic cancer cells and their carrier's plasma, pancreas, and liver. We transplanted MiaPaCa2 human pancreatic cancer cells in athymic mice and fed them normal diet or four HFDs enriched with SFA, MUFA, n6PUFA, and n3PUFA, respectively. After 7 weeks, fatty acids were profiled in tumor, plasma, pancreas, and liver, using gas chromatography. When tumor carriers were fed four HFDs, the fatty acids that were increased dietarily were also increased in the plasma. When tumor carriers were fed MUFA-, n6PUFA-, and n3PUFA-enriched HFDs, the dietarily increased fatty acids were also increased in tumor, pancreas, and liver. When tumor-carriers were fed the SFA-enriched HFD featuring lauric and myristic acids (C12:0 and C14:0), tumor, pancreas, and liver showed an increase not in the same SFAs but palmitic acid (C16:0) and/or stearic acid (C18:0). In conclusion, predominant fatty acids in HFDs determine the fatty-acid profiles of pancreatic cancer cells and their murine carriers.
The results of studies on the relationship between cytokine polymorphisms and polycystic ovary syndrome (PCOS) have been controversial. This meta-analysis was thus designed to more precisely assess the relationship between TNF-alpha/IL-1/ IL-6/IL-10 polymorphisms and PCOS by pooling the results of published studies. A search of PubMed, Embase, Web of Science, and CNKI databases turned up 23 studies that were pooled and analyzed in this meta-analysis. The overall results showed that the distributions of TNF-alpha -238 G/A, TNF-alpha -857 C/T, and IL-1B -51 C/T polymorphisms among patients and controls differed significantly. Additionally, the distributions of TNF-alpha -308 G/A and IL-1B -51 C/T polymorphisms among patients and controls from Asian populations differed significantly, whereas the distributions of IL-6 -174 G/C and IL-1A -889 C/T polymorphisms among patients and controls from Caucasian populations also differed significantly. In conclusion, our meta-analysis demonstrated that TNF-alpha -238 G/A, TNF-alpha -857 C/T, and IL-1B -51 C/T polymorphisms might influence susceptibility to PCOS in the overall pooled population. Moreover, TNF-alpha -308 G/A and IL-1B -51 C/T polymorphisms might influence susceptibility to PCOS in Asians, whereas IL-6 -174 G/C and IL-1A -889 C/T polymorphisms might influence to PCOS in Caucasians.
This study aimed to analyze the effect of the severity of obstructive sleep apnea-hypopnea syndrome (OSAHS) on diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). A total of 322 patients with T2DM participated in this cross-sectional study. OSAHS was diagnosed according to the apnea-hypopnea index (AHI) and it was categorized as follows: normal, mild, moderate, and severe. Relevant clinical data retrieved from medical charts were cross-analyzed between different groups. The relationship between urinary albumin/creatinine ratio(UACR) and OSAHS parameters, which included AHI, lowest oxygen saturation (L-SaO(2)), and mean oxygen saturation (M-SaO(2)), was evaluated by partial correlation analysis. DN stages were classified into a non-DN group, a microalbuminuria group, and a macroalbuminuria group. Multiple factor logistic regression analysis was employed to analyze factors influencing DN. The results showed that mild OSAHS, moderate OSAHS, and severe OSAHS patients had a higher Body mass index (BMI), creatinine (CR) level, UACR, and a longer duration of T2DM (p < 0.05) than the non-OSAHS group. The prevalence of DN in the non-OSAHS, mild OSAHS, moderate OSAHS, and severe OSAHS groups was 18.4%, 19.2%, 34.6%, and 49.4%, respectively (p < 0.05). Multiple factor logistic regression analysis revealed that systolic blood pressure (SBP) (OR = 1.03), AHI (OR = 1.02), and duration of T2DM (OR = 1.04) were correlated with DN (p < 0.05). These findings revealed that OSAHS is highly prevalent in T2DM and AHI is independently associated with the presence of DN.
Obstructive sleep apnea (OSA), characterized by recurrent episodes of apnea during sleep and daytime sleepiness, seriously affects human health and may lead to systemic organ dysfunction. The pathogenesis of OSA is complex and still uncertain, but multiple surveys have shown that obesity is an important factor, and the incidence of OSA in people with obesity is as high as 30%. Adipokines are a group of proteins secreted from adipocytes, which are dysregulated in obesity and may contribute to OSA. Here, we review the most important and representative research results regarding the correlation between obesity-related adipokines including leptin, adiponectin, omentin-1, chemerin, and resistin and OSA in the past 5 years, provide an overview of these key adipokines, and analyze possible intrinsic mechanisms and influencing factors. The existing research shows that OSA is associated with an increase in the serum levels of leptin, chemerin, and resistin and a decrease in the levels of adiponectin and omentin-1; the findings presented here can be used to monitor the development of OSA and obesity, prevent future comorbidities, and identify risk factors for cardiovascular and other diseases, while different adipokines can be linked to OSA through different pathways such as insulin resistance, intermittent hypoxia, and inflammation, among others. We hope our review leads to a deeper and more comprehensive understanding of OSA based on the relevant literature, which will also provide directions for future clinical research.
Obesity is strongly correlated with the pathogenesis of obstructive sleep apnea (OSA); myokines may play important roles in this condition. We performed a body mass index-(BMI) and physical activity-(PA) matched study to explore the relationship between the irisin level and OSA. Ninety-six consecutive participants were recruited. After matching in terms of BMI and PA, 28 OSA patients and 28 healthy controls were finally included. Whole-night laboratory-based polysomnography was used to identify OSA. The Recent Physical Activity Questionnaire and Epworth Sleepiness Scale Questionnaire were employed to assess PA over the past 4 weeks, and daytime sleepiness. We measured serum irisin, fasting blood glucose, and insulin levels in blood samples. The serum irisin concentrations differed significantly between the control, mild OSA, moderate OSA, and severe OSA groups (p < 0.001) and correlated significantly with the apnea/hypopnea index (AHI) (r = -0.787, p < 0.001). All of age, BMI, neck, waist and hip circumferences, fasting blood glucose level, and the Epworth Sleepiness Scale and PA scores were associated with irisin levels (p < 0.05). After adjustment for these factors, the serum irisin level was independently correlated with the AHI (r = -0.428, p = 0.002). On forward logistic regression analysis, the association remained significant in the final multiple regression model (beta = -0.107, p < 0.001). The serum irisin concentration was significantly correlated with OSA severity, independently of BMI and PA. Further studies are needed to determine the molecular mechanisms in play.
Thyroid hormone is crucial for regulating lipid and glucose metabolism, which plays essential role in maintaining the health of pregnant women and their offspring. However, the current literature is just focusing on the development of offspring born to the untreated mothers with hypothyroidism, rather than mothers themselves. Additionally, the interaction between hypothyroidism and pregnancy, and its impact on the women's health are still elusive. Therefore, this study was designed to compare the metabolic differences in dams with hypothyroidism starting before pregnancy and after pregnancy. Pre-pregnant hypothyroidism was generated in 5-week-old female C57/BL/6J mice using iodine-deficient diet containing 0.15% propylthiouracil for 4 weeks, and the hypothyroidism was maintained until delivery. Gestational hypothyroidism was induced in dams after mating, using the same diet intervention until delivery. Compared with normal control, gestational hypothyroidism exhibited more prominent increase than pre-pregnant hypothyroidism in plasma total cholesterol and low -density lipoprotein cholesterol, and caused hepatic triglycerides accumulation. Similarly, more significant elevations of protein expressions of SREBP1c andp-ACL, while more dramatic inhibition of CPT1A and LDL-R levels were also observed in murine livers with gestational hypothyroidism than those with pre-pregnant hypothyroidism. Moreover, the murine hepatic levels of total cholesterol and gluconeogenesis were dramatically and equally enhanced in two hypothyroid groups, while plasma triglycerides and protein expressions of p-AKT, p-FoxO1 and APOC3 were reduced substantially in two hypothyroid groups. Taken together, our current study illuminated that gestational hypothyroidism may elicit more pronounced lipid dysregulation in dams than dose the pre-pregnant hypothyroidism.
Stem cells (SCs) therapy is a new promising therapeutic modality for type 1 diabetes (T1DM). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of stem cells transplantation (SCT) in patients with T1DM. We searched five literature databases (MEDLINE, EMBASE, Web of Science, WanFang and CENTRAL) up to 31 October 2019. 29 studies (487 patients with T1DM) were included in our meta-analysis. There was no substantial publication bias. Meta-analysis showed the SCT had significant effect to decrease HbA1c (SMD, 1.40; 95% CI, 0.93 to 1.86; p < 0.00001; I-2 = 89%) and to improve C-peptide levels (SMD, -0.62; 95% CI, -1.22 to -0.02; p = 0.04; I-2 = 92%) at 1 year follow-up. Subgroup analyses showed the heterogeneity level of the results was high. Significant improvement of metabolic outcomes was observed in the subgroups of mesenchymal stem cells (MSCs) combined with hematopoietic stem cells (HSCs) and HSCs. The older age showed significant association with the efficacy in HSCs subgroup. The higher GADA positive rate before treatment also significantly associated with the decrease of daily insulin requirement. The transient insulin independence rate at last follow-up was 9.6 per 100 person-years (95% CI: 5.8-13.5%). The mean length of insulin independence was 15.6 months (95% CI: 12.3-18.9). The mortality of SCT was 3.4% (95% CI: 2.1-5.5%). Therefore, SCT is an efficacious and safe method for treating patients with T1DM especially in the subgroups of MSCs + HSCs and HSCs. Well designed, double blind and randomized controlled trails with large sample size and long-term follow-up are needed for further evaluation.
This study aims to investigate the prevalence of islet autoantibodies and other organ-specific autoantibodies in type 1 diabetes mellitus (T1DM) patients and characterize their clinical features. Glutamic acid decarboxylase antibody (GADA), insulinoma antigen 2 antibody (IA-2A), zinc transporter 8 antibody (ZnT8A) and tetraspanin7 antibody (TSPAN7A) were assayed by radioligand or luciferase immunoprecipitation system assays in 205 newly diagnosed acute-onset T1DM patients and 170 healthy controls. Other organ-specific autoantibodies, including thyroid peroxidase antibody (TPOA), thyroglobulin antibody (TGA), tissue transglutaminase antibody (tTGA) and 21-hydroxylase antibody (21-OHA), were also measured. The prevalence of GADA, IA-2A, ZnT8A, TSPAN7A, TPOA, TGA and 21-OHA was higher in T1DM patients than in healthy controls. The combinational assay of various islet autoantibodies could increase the frequency of autoantibody positivity in T1DM to 85.4%. GADA+ IA-2A+ T1DM patients preferentially had TPOA and TGA, while IA-2A+ patients often had tTGA. Patients positive for two or more islet autoantibodies often had TPOA and TGA. BMI of multiple islet autoantibody-positive patients was lower than that of patients with single or no islet autoantibodies, and there were no significant differences in C-peptide and glycated hemoglobin between patients positive for islet autoantibodies combined with other organ-specific antibodies and noncombined patients. Younger female patients who were islet autoantibody positive were more likely to have TPOA and TGA. The frequency of Graves' disease was much higher in T1DM patients than in healthy controls. T1DM usually occurs together with other organ-specific autoantibodies. Measuring of other organ-specific autoantibodies will be beneficial for T1DM patients.