Mesophilic Argonaute-Based Single Polystyrene Sphere Aptamer Fluorescence Platform for the Multiplexed and Ultrasensitive Detection of Non-Nucleic Acid Targets.

The rapid, simultaneous, and accurate identification of multiple non-nucleic acid targets in clinical or food samples at room temperature is essential for public health. Argonautes (Agos) are guided, programmable, target-activated, next-generation nucleic acid endonucleases that could realize one-pot and multiplexed detection using a single enzyme, which cannot be achieved with CRISPR/Cas. However, currently reported thermophilic Ago-based multi-detection sensors are mainly employed in the detection of nucleic acids. Herein, this work proposes a Mesophilic Argonaute Report-based single millimeter Polystyrene Sphere (MARPS) multiplex detection platform for the simultaneous analysis of non-nucleic acid targets. The aptamer is utilized as the recognition element, and a single millimeter-sized polystyrene sphere (PSmm ) with a large concentration of guide DNA on the surface served as the microreactor. These are combined with precise Clostridium butyricum Ago (CbAgo) cleavage and exonuclease I (Exo I) signal amplification to achieve the efficient and sensitive recognition of non-nucleic acid targets, such as mycotoxins (<60 pg mL-1 ) and pathogenic bacteria (<102 cfu mL-1 ). The novel MARPS platform is the first to use mesophilic Agos for the multiplex detection of non-nucleic acid targets, overcoming the limitations of CRISPR/Cas in this regard and representing a major advancement in non-nucleic acid target detection using a gene-editing-based system.

Machine learning algorithms are comparable to conventional regression models in predicting distant metastasis of follicular thyroid carcinoma.

OBJECTIVE: Distant metastasis often indicates a poor prognosis, so early screening and diagnosis play a significant role. Our study aims to construct and verify a predictive model based on machine learning (ML) algorithms that can estimate the risk of distant metastasis of newly diagnosed follicular thyroid carcinoma (FTC). DESIGN: This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. PATIENTS: A total of 5809 FTC patients were included in the data analysis. Among them, there were 214 (3.68%) cases with distant metastasis. METHOD: Univariate and multivariate logistic regression (LR) analyses were used to determine independent risk factors. Seven commonly used ML algorithms were applied for predictive model construction. We used the area under the receiver-operating characteristic (AUROC) curve to select the best ML algorithm. The optimal model was trained through 10-fold cross-validation and visualized by SHapley Additive exPlanations (SHAP). Finally, we compared it with the traditional LR method. RESULTS: In terms of predicting distant metastasis, the AUROCs of the seven ML algorithms were 0.746-0.836 in the test set. Among them, the Extreme Gradient Boosting (XGBoost) had the best prediction performance, with an AUROC of 0.836 (95% confidence interval [CI]: 0.775-0.897). After 10-fold cross-validation, its predictive power could reach the best [AUROC: 0.855 (95% CI: 0.803-0.906)], which was slightly higher than the classic binary LR model [AUROC: 0.845 (95% CI: 0.818-0.873)]. CONCLUSIONS: The XGBoost approach was comparable to the conventional LR method for predicting the risk of distant metastasis for FTC.

Klotho reduces the risk of osteoporosis in postmenopausal women: a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Osteoporosis (OP) is one of the diseases that endanger the health of the elderly population. Klotho protein is a hormone with anti-aging effects. A few studies have discussed the relationship between Klotho and OP. However, there is still a lack of research on larger populations. This study aims to evaluate the association between OP and Klotho in American postmenopausal women. METHODS: This is a retrospective study. We searched the National Health and Nutrition Examination Survey (NHANES) database and collected data of 3 survey cycles, finally involving 871 postmenopausal women over 50 years old in the present study. All participants took dual-energy X-ray absorptiometry examination and serum Klotho testing at the time of investigation. After adjusting the possible confounding variables, a multivariate regression model was employed to estimate the relationship between OP and Klotho proteins. Besides, the P for trend and restricted cubic spline (RCS) were applied to examine the threshold effect and calculate the inflection point. RESULTS: Factors influencing the occurrence of OP included age, ethnicity, body mass index and Klotho levels. Multivariate regression analysis indicated that the serum Klotho concentration was lower in OP patients than that in participants without OP (OR[log2Klotho] = 0.568, P = 0.027). The C-index of the prediction model built was 0.765, indicating good prediction performance. After adjusting the above-mentioned four variables, P values for trend showed significant differences between groups. RCSs revealed that when the Klotho concentration reached 824.09 pg/ml, the risk of OP decreased drastically. CONCLUSION: Based on the analysis of the data collected from the NHANES database, we propose a correlation between Klotho and postmenopausal OP. A higher serum Klotho level is related to a lower incidence of OP. The findings of the present study can provide guidance for research on diagnosis and risk assessment of OP.

Combined T4 + T3 therapy versus T4 monotherapy effect on psychological health in hypothyroidism: A systematic review and meta-analysis.

PURPOSE: To evaluate whether T4 + T3 combination therapy had advantages in improving psychological health compared with T4 monotherapy. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science from January 2000 to March 2021, and updated in September 2021. The inclusion criteria (prospective study, published in English, had a T4 + T3 combination therapy test group and a T4 monotherapy control group, patients aged ≥18 years and with overt primary hypothyroidism, and published after January 2000) were applied by two reviewers; any disagreement was resolved by a third reviewer. The two reviewers independently extracted data using a standard data form and assessed the risk of bias using the Cochrane risk of bias tool. Coprimary outcomes included the psychological health measures of depression, fatigue, pain, anxiety and anger, measured using validated and reliable instruments. RESULTS: Eighteen of 2029 studies (883 patients) were included in the meta-analysis. No significant difference was found between T4 + T3 combination therapy and T4 monotherapy with regard to depression (standardized mean difference [SMD]: -0.06, 95% confidence interval [CI]: -0.18; 0.07), fatigue (SMD: 0.06, 95% CI: -0.13; 0.26), pain (SMD: -0.01, 95% CI: -0.24; 0.22), anxiety (SMD: 0.01, 95% CI: -0.15; 0.17) and anger (SMD: 0.05, 95% CI: -0.15; 0.24). Methodological heterogeneity had no influence on the results. The patients preferred combination therapy significantly. CONCLUSIONS: Compared with T4 monotherapy, T4 + T3 combination therapy had no significant advantage in improving psychological health. For patients who are unsatisfied with LT4 monotherapy, the patient and the physician should make a joint decision concerning therapy.

Association of soy food with cardiovascular outcomes and all-cause mortality in a Chinese population: a nationwide prospective cohort study.

PURPOSE: This study aimed to clarify the association of soy intake with cardiovascular disease (CVD) and all-cause mortality. METHODS: We conducted a prospective cohort study in a Chinese population composed of 97,930 participants aged ≥ 40 years old without CVD at baseline in 2011. Habitual soy intake over a period of 12 months was evaluated using a food frequency questionnaire. All participants were classified into four groups based on their soy food consumption levels: < 15, 15-29, 30-59, and ≥ 60 g/day, with the lowest category as the reference group. Follow-up was conducted between 2014 and 2016 to assess CVD incidence and all-cause mortality since baseline, which was collected from the local mortality and disease registers of the National Disease Surveillance Point System and National Health Insurance System. The Cox proportional hazards regression models were used to analyze the relationship of soy intake with later CVD events and all-cause mortality. RESULTS: During 350,604 person-years of follow-up (median [interquartile range]: 3.16 [2.98, 4.77] years), 2523 total CVD events and 1473 all-cause mortalities were documented. After controlling for covariates, the hazard ratios (95% confidence intervals) for total CVD events across increasing soy intake levels were 1.03 (0.93-1.14); 0.96 (0.86-1.07); and 0.86 (0.75-0.98; p for trend = 0.0434), while those for all-cause mortality were 0.88 (0.77-1.02); 0.86 (0.74-1.00); and 0.83 (0.69-0.99; p for trend = 0.0084). CONCLUSION: High soy intake was associated with a reduced risk of total CVD events and all-cause mortality among a Chinese population.

Exploring risk factors for cervical lymph node metastasis in papillary thyroid microcarcinoma: construction of a novel population-based predictive model.

BACKGROUND: Machine learning was a highly effective tool in model construction. We aim to establish a machine learning-based predictive model for predicting the cervical lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC). METHODS: We obtained data on PTMC from the SEER database, including 10 demographic and clinicopathological characteristics. Univariate and multivariate logistic regression (LR) analyses were applied to screen the risk factors for cervical LNM in PTMC. Risk factors with P < 0.05 in multivariate LR analysis were used as modeling variables. Five different machine learning (ML) algorithms including extreme gradient boosting (XGBoost), random forest (RF), adaptive boosting (AdaBoost), gaussian naive bayes (GNB) and multi-layer perceptron (MLP) and traditional regression analysis were used to construct the prediction model. Finally, the area under the receiver operating characteristic (AUROC) curve was used to compare the model performance. RESULTS: Through univariate and multivariate LR analysis, we screened out 9 independent risk factors most closely associated with cervical LNM in PTMC, including age, sex, race, marital status, region, histology, tumor size, and extrathyroidal extension (ETE) and multifocality. We used these risk factors to build an ML prediction model, in which the AUROC value of the XGBoost algorithm was higher than the other 4 ML algorithms and was the best ML model. We optimized the XGBoost algorithm through 10-fold cross-validation, and its best performance on the training set (AUROC: 0.809, 95%CI 0.800-0.818) was better than traditional LR analysis (AUROC: 0.780, 95%CI 0.772-0.787). CONCLUSIONS: ML algorithms have good predictive performance, especially the XGBoost algorithm. With the continuous development of artificial intelligence, ML algorithms have broad prospects in clinical prognosis prediction.

Associations of early-life exposure to famine with abdominal fat accumulation are independent of family history of diabetes and physical activity.

The present study aimed to investigate the association of early-life exposure to famine with abdominal fat accumulation and function and further evaluate the influence of first-degree family history of diabetes and physical activity on this association. The present work analysed parts of the REACTION study. A total of 3033 women were enrolled. Central obesity was defined as waist circumferences (W) ≥ 85 cm. Chinese visceral adiposity index (CVAI) was used to evaluate visceral adipose distribution and function. Partial correlation analysis showed BMI, W, glycated Hb and CVAI were associated with early-life exposure to famine (both P < 0·05). Logistic regression showed that the risks of overall overweight/obesity and central obesity in fetal, early-childhood, mid-childhood and late-childhood exposed subgroups were increased significantly (all P < 0·05). Compared with the non-exposed group, the BMI, W and CVAI of fetal, early- to late-childhood exposed subgroups were significantly increased both in those with or without first-degree family history of diabetes and in those classified as physically active or inactive, respectively (all P < 0·05). The associations of BMI, W and CVAI with early-life exposure to famine were independent of their associations with first-degree family history of diabetes (all P < 0·01) or physical activity status (all P < 0·001). Early-life exposure to famine contributed to abdominal fat accumulation and dysfunction, which was independent of the influence of genetic background and exercise habits. Physical activity could serve as a supplementary intervention for women with high risk of central obesity.

Dietary inflammatory index and cardiorenal function in women with diabetes and prediabetes.

BACKGROUND AND AIMS: Previous studies had shed a new light on the importance of multiple inflammatory mechanisms in the pathogenesis of arterial stiffness. The dietary inflammatory index (DII®) is a new tool for estimating the overall inflammatory potential of the diet. The aim of this study is to assess the association of the inflammatory potential of diet with peripheral arterial stiffness and renal function in women with diabetes and prediabetes. METHODS AND RESULTS: This is an observational cross-sectional study. A total of 2644 females aged 45-75 years were included for the study. Dietary intake in the past 12 months was assessed by a validated China National Nutrition and Health Survey 2002 (CNHS2002) food-frequency questionnaire. Energy-adjusted DII (E-DII) scores were calculated from daily dietary information. In a multivariable linear regression analysis adjusted for potential confounders, E-DII was positively associated with brachial ankle pulse wave velocity (baPWV) in participants with diabetes (ß = 12.820; 95% CI = 2.565, 23.076; P = 0.014) and prediabetes (ß = 29.025; 95% CI = 1.110, 56.940; P = 0.042), but not in females with normal glucose homeostasis. In addition, per unit increase of E-DII was significantly associated with lower eGFR (ß = -1.363; 95% CI = -2.335, -0.392; P = 0.006) in patients with diabetes. CONCLUSION: We identified a direct association between E-DII and arterial stiffness, decreasedeGFR in middle-aged and elderly women with diabetes or prediabetes. Future studies are needed to verify and clarify the role of E-DII as an intervention target for cardiorenal complications of chronic hyperglycemia.

Efficacy and safety of prenatal dexamethasone treatment in offspring at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of prenatal dexamethasone treatment in offspring at risk for congenital adrenal hyperplasia. METHODS: MEDLINE, EMBASE, the Cochrane Library, the clinicaltrials.gov website databases were systematically searched from inception through March 2019. WMD and SMD with 95%CIs were calculated using random or fixed effects models. RESULTS: There was a significant reduction in virilization in the DEX-treated group (WMD: -2.39, 95%CI: -3.31,-1.47). No significant differences were found in newborn physical outcomes for birth weight (WMD: 0.09, 95%CI: -0.09, 0.27) and birth length (WMD = 0.27, 95%CI: -0.68, 1.21). Concerning cognitive functions, no significant differences in the domains of psychometric intelligence (SMD: 0.05, 95%CI: -0.74, 0.83), verbal memory (SMD: -0.17, 95%CI: -0.58, 0.23), visual memory (SMD: 0.10, 95%CI: -0.14, 0.34), learning (SMD: -0.02, 95%CI: -0.27, 0.22) and verbal processing (SMD: -0.38, 95%CI: -0.93, 0.17). Regarding behavioural problems, no significant differences in the domains of internalizing problems (SMD: 0.16, 95%CI: -0.49, 0.81), externalizing problems (SMD: 0.07, 95%CI: -0.30, 0.43) and total problems (SMD: 0.14, 95%CI: -0.23, 0.51). With respect to temperament, no significant differences in the domains of emotionality (SMD: 0.13, 95%CI: -0.79, 1.05), activity (SMD: 0.04, 95%CI: -0.32, 0.39), shyness (SMD: 0.25, 95%CI: -0.70, 1.20) and sociability (SMD: -0.23, 95%CI: -0.90, 0.44). CONCLUSIONS: Prenatal DEX treatment reduced virilization with no significant differences in newborn physical outcomes, cognitive functions, behavioural problems and temperament. The results need to be interpreted cautiously due to the existence of limitations.

Opposite effects of high- and low-dose di-(2-ethylhexyl) phthalate (DEHP) exposure on puberty onset, oestrous cycle regularity and hypothalamic kisspeptin expression in female rats.

Di-(2-ethylhexyl) phthalate (DEHP) is ubiquitous in the environment and has been proposed to lead to reproductive disruption. In this study, we systematically investigated the effects of different doses of DEHP exposure on female hypothalamic-pituitary-gonadal axis development. Female Sprague-Dawley rats were gavaged with vehicle (corn oil) or DEHP (5 or 500mgkg-1 day-1) during postnatal Days (PNDs) 22-28 or PNDs 22-70. Results demonstrated that the low and high doses of DEHP exerted opposite effects on puberty onset, circulating luteinising hormone, serum oestradiol and progesterone levels, with the low dose (5mgkg-1) promoting and the high dose (500mgkg-1) inhibiting these parameters. Significant dose-related differences were also found in the D500 group with longer oestrous cycle duration, lower ovarian/bodyweight ratio, fewer corpus lutea and more abnormal ovarian stromal tissue in comparison with the oil or D5 groups. Molecular data showed that the hypothalamic Kiss1 mRNA expression in the anteroventral periventricular but not in the arcuate nucleus significantly decreased in the D500 rats and increased in the D5 rats relative to the rats in the oil group. These findings suggested that the kisspeptin system is a potential target for DEHP to disrupt reproductive development and function.

Comparing Stereotactic Radiosurgery and Fractionated Stereotactic Radiotherapy in Treating patients with Growth Hormone-Secreting Adenomas: A Systematic Review and Meta-analysis.

Context: Radiotherapy for patients with acromegaly was considered when patients have residual disease or tumor recurrence after surgery, or when surgery can't be carried out. There are two main modes of radiotherapy, including stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). Objective: We conducted a systematic review and meta-analysis to present the effectiveness and safety of SRS and FSRT for GH secreting pituitary adenoma in clinical practice. Methods: We searched the published literature using following databases: Pub Med, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and EMBASE up to March 22, 2020, for studies in which SRS or FSRT were used in patients with GH secreting pituitary. Results: A total of 33 studies were eligible, involving 2016 participants. No significant differences were observed in tumor shrinkage rate, local tumor control rate and adverse effect rate between SRS and FSRT. Compared to FSRT, SRS showed significant increase in biochemical remission rate (43% vs. 28%; p=0.023) and significant lower follow-up GH level (SMD: -1.20 vs. -0.37, p=0.006). Conclusions: SRS and FSRT showed comparable effectiveness and safety in the management of GH secreting pituitary adenoma patients. SRS might be associated with better biochemical remission.

The predictive value of procalcitonin for early detection of infection in elderly type 2 diabetes mellitus.

OBJECTIVE: Aimed to investigate the predictive value of procalcitonin (PCT) in early detection of infections in elderly patients with type 2 diabetes, and to discover the optimum cut-off points of PCT. METHODS: A retrospective study was conducted with type 2 diabetic patients (≥65 years) with lung infection (LI), urinary tract infection (UTI) or skin and soft tissue infection (SSTI). The receiver operating characteristic (ROC) curves of the 3 markers (PCT, WBC count, and CRP) were constructed and compared to assess their accuracies in diagnosing. RESULTS: Among the three different groups with LI, UTI or SSTI, the area under the ROC curve (AUC) of PCT was 0.98 (95% confidence interval (CI): 0.96-0.99, p < 0.05) for the LI group, 0.98 (95% CI: 0.96-0.99, p < 0.05) for the UTI group, and 0.97 (95% CI: 0.94-1.00, p < 0.05) for the SSTI group. The optimum cut-off point of PCT level was 0.73 ng/mL (Sn 89.7%, Sp 97.7%) for the LI group, 1.48 ng/mL (Sn 88.9%, Sp 100%) for the UTI group, and 0.73 ng/mL (Sn 85.7%, Sp 97.7%) for the SSTI group. CONCLUSION: PCT demonstrated the strongest correlation with each of the infection types, indicating significant diagnostic value. Optimum cut-off points of PCT levels in elderly diabetes were higher.

Association between lifestyle and thyroid dysfunction: a cross-sectional epidemiologic study in the She ethnic minority group of Fujian Province in China.

BACKGROUND: Thyroid dysfunction is one of the prevalent endocrine disorders. The relationship between lifestyle factors and thyroid dysfunction was not clear and some of the factors seemed paradoxical. METHODS: We conducted this population-based study using data from 5154 She ethnic minority people who had entered into the epidemic survey of diabetes between July 2007 to September 2009. Life style information was collected using a standard questionnaire. Body mass index (BMI), Blood pressure and serum TSH, TPOAb, triglycerides (TG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL) were collected. RESULTS: The study showed that people who drank, had higher education or suffered from insomnia have lower incidence of hyperthyroidism. On the other hand, smoking, alcohol consumption, exercise, undergoing weight watch and chronic headache were associated with decreased incidence of hypothyroidism. Using multivariable logistic regression analysis, we found that alcohol consumption was associated with decreased probability of hyperthyroidism, hypothyroidism, as well as positive TPOAb. The amounts of cigarettes smoked daily displayed a positive correlation with hyperthyroidism among smokers. Accordingly, smoking seemed to be associated with decreased risk for hypothyroidism and positive TPOAb. Exercise and maintaining a healthy weight might have a beneficial effect on thyroid health. Interestingly, daily staple amount showed an inverse correlation with incidence of positive TPOAb. CONCLUSIONS: Within the Chinese She ethnic minority, we found associations between different lifestyle factors and the incidence of different thyroid diseases. Understanding the nature of these associations requires further investigations.

Association between Depression and Renal Hyperfiltration in a General Chinese Population.

BACKGROUND: Depression is prevalent in patients with all stages of CKD and is associated with adverse outcome. Abnormally elevated GFR, or hyperfiltration, may play a crucial role in the initiation and progression of CKD. However, the association between depression and hyperfiltration is not known. The aim of this study is to investigate the relationship between depression and hyperfiltration. METHODS: This was an observational cross-sectional study. A total of 3,716 volunteers (1,303 males and 2,413 females) aged 40-75 years without CKD from a community in China were included for the study. Depressive symptoms and the presence of a minor or major depressive episode were assessed with the 9-item Patient Health Questionnaire (PHQ-9) and Diagnostic and Statistical Manual of Mental Disorders (4th edition)-based structured interview, respectively. RESULTS: The mean age of the participants in the present study was 53.8 ± 9.0 years. 115 participants had clinically relevant depression, and 122 participants had a minor or major depressive episode. In a multivariable logistic regression analysis adjusted for potential confounders, the association between clinically relevant depression and renal hyperfiltration remained significant in men but not in women. As compared with men without depression (PHQ <5) or depressive episodes, those with clinically relevant depression (PHQ ≥10) had a significantly higher risk of renal hyperfiltration. The fully adjusted OR (95% CI) was 4.81 (1.62-14.30, p = 0.005), those with a major depressive episode had a higher risk of renal hyperfiltration (OR 7.45; 95% CI 2.04-27.21, p = 0.002). CONCLUSION: Depressive symptoms and major depressive episodes are associated with renal hyperfiltration in middle-aged and elderly Chinese men without CKD. Future studies are needed to verify and clarify the role of depression in the development of abnormally high eGFR and CKD.

EXPOSURE TO FAMINE IN EARLY LIFE AND THE RISK OF OSTEOPOROSIS IN ADULTHOOD: A PROSPECTIVE STUDY.

Objective: To assess the association between famine exposure in early life and osteoporosis in adulthood. Methods: A total of 2,292 participants born between 1955 and 1965 in Fujian Province were selected; after 3 years, 1,378 participants attended a follow-up research visit. Calcaneus bone mineral density and bone quality were measured by quantitative ultrasound. The T-score was used to assess bone mineral density, and the parameters quantitative ultrasound index (QUI), speed of sound (SOS), and broadband ultrasonic attenuation (BUA) were used to assess bone quality. A T-score threshold of -1.8 was defined as osteoporosis, and a possible vertebral fracture was considered as a prospective height loss of 0.8 inches or more. Results: Compared with the nonexposed cohort, risks of osteoporosis for fetal-, early childhood, and mid-childhood famine-exposed cohorts in postmenopausal women were adjusted odds ratio (OR), 3.741 (95% confidence interval [CI], 1.233, 11.44) versus OR 2.894 (95% CI, 0.997, 8.571) versus OR 4.699 (95% CI, 1.622, 13.612) by logistic regression but not significant in men. Moreover, the fetal-exposed cohort had a weak negative relation with QUI (ß, -5.07 [-10.226, 0.127]) and BUA (ß, -4.321 [-0.88, 0.238]). The early- and mid-childhood-exposed cohorts had significantly lower QUI (ß, -7.085 [-11.799, -2.372] versus ß, -10.845 [-15.68, -6.01]) and BUA (ß, -6.381 [-10.515, -2.246] versus ß, -8.573 [-12.815, -4.331]) than the nonexposed cohort by linear regression. None of the famine-exposed cohorts had a significant relationship with SOS. Conclusion: Famine exposure during early life is associated with higher risk of osteoporosis in adulthood, which is most obvious in postmenopausal women. Furthermore, famine exposure in early life has adverse effects on bone quality. Abbreviations: BMD = bone mineral density; BUA = broadband ultrasonic attenuation; CI = confidence interval; OR = odds ratio; QUI = quantitative ultrasound index; QUS = quantitative ultrasound; SOS = speed of sound.

RAGE Gly82Ser polymorphism in patients with type 2 diabetes with comorbid Depression.

OBJECTIVE: To examine receptors for advanced glycation end-products Gly82Ser polymorphism in patients of type 2 diabetes with comorbid depression. METHODS: The case-control study was conducted at Fujian Provincial Hospital, Fuzhou, China, between December 2011 and December 2012, and comprised unrelated Chinese Han patients of type 2 diabetes, and diabetics with diagnosed clinical depression. Gly82Ser polymorphism polymorphism was determined using polymerase chain reaction amplification-high resolution melting curve protocol. Serum levels of endogenous secretory receptor for advanced glycation end products were measured using enzyme-linked immunosorbent assay. SPSS 16 was used for data analysis. RESULTS: Of the 114 subjects, 72(63.15%) were clinically depressed. Lower levels of endogenous secretory receptor were found in the depression group compared with the other group (p=0.049). No difference in genotypes or allele frequencies existed between the two groups (p>0.05). Gly82Ser carriers had significantly higher Hamilton Rating Scale scores (p<0.001) and lower serum endogenous secretory receptor (p=0.012) among the depressed diabetics. There were also significant differences in body mass index (p=0.005), abdominal circumference (p=0.038), carotid intima-media thickness (p=0.037) and high-sensitivity C-reactive protein (p=0.005) concentration between the different genotypes.. CONCLUSIONS: Receptors for advanced glycation end-products-ligands system may be involved in type 2 diabetes with comorbid depression at the genetic level.

Self-reported sleep duration and daytime napping are associated with renal hyperfiltration in general population.

STUDY OBJECTIVES: Renal hyperfiltration (RHF) has emerged as a novel marker of early renal damage in various conditions such as diabetes and metabolic syndrome. Aberrant sleep duration and excessive daytime napping may affect the development of chronic kidney disease (CKD). In this study, the association between sleep duration, daytime napping, and renal hyperfiltration was assessed. SETTING: This study was conducted in three communities in China. PARTICIPANTS: A total of 16,119 community volunteers (5735 males and 10,384 females) aged 40-65 years without CKD were included for the study. METHODS AND RESULTS: Participants with short sleep duration (<6 h/day) or long sleep duration (≥10 h/day) were at a significantly increased risk of renal hyperfiltration. The fully adjusted ORs (95% CI) were 2.112 (1.107, 4.031) and 2.071 (1.504, 2.853), respectively (P < 0.05). In addition, those who took naps longer than 1.5 h per day had a higher risk of renal hyperfiltration compared with those without napping (OR 1.400, 95% CI 1.018-1.924). Further joint analysis indicated that participants with long sleep duration (≥10 h/day) had a more than twofold increased risk of RHF regardless of nap status compared with those who slept 8-9 h per day without daytime napping. The association between sleep duration or daytime napping and RHF could not be explained by the influence of sleep quality. Additional subgroup analysis showed long sleep duration (≥9 h/day) and long daytime napping (≥1.5 h) were associated with an increased risk of RHF among individuals with good sleep quality. CONCLUSION: Sleep duration less than 6 h/day or more than 10 h/day and long daytime napping tend to be associated with an increased risk of renal hyperfiltration in middle-aged general population, and this relationship was independent of diabetes, hypertension, obesity, or poor sleep quality.

Computational Analysis of Missense Variants of G Protein-Coupled Receptors Involved in the Neuroendocrine Regulation of Reproduction.

INTRODUCTION: Many missense variants in G protein-coupled receptors (GPCRs) involved in the neuroendocrine regulation of reproduction have been identified by phenotype-driven or large-scale exome sequencing. Computational functional prediction analysis is commonly performed to evaluate their impact on receptor function. METHODS: To assess the performance and outcome of functional prediction analyses for these GPCRs, we performed a statistical analysis of the prediction performance of SIFT and PolyPhen-2 for variants with documented biological function as well as variants retrieved from Ensembl. We obtained missense variants with documented biological function testing from patients with reproductive disorders from a comprehensive literature search. Missense variants from individuals with known reproductive disorders were retrieved from the Human Gene Mutation Database. Missense variants from the general population were retrieved from the Ensembl genome database. RESULTS: The accuracies of SIFT and PolyPhen-2 were 83 and 85%, respectively. The performance of both prediction tools was greater in predicting loss-of-function variants (SIFT: 92%; PolyPhen-2: 95%) than in predicting variants that did not affect function (SIFT: 54%; PolyPhen-2: 57%). Concordance between SIFT and PolyPhen-2 did not improve accuracy. Surprisingly, approximately half of the variants retrieved from Ensembl were predicted as loss-of-function variants by SIFT (47%) and PolyPhen-2 (54%). CONCLUSION: Our findings provide new guidance for interpreting the results and limitations of computational functional prediction analyses for GPCRs and will help to determine which variants require biological function testing. In addition, our findings raise important questions regarding the link between genotype and phenotype in the general population.

Immunohistochemical identification of osteoclasts and multinucleated macrophages.

Osteoclasts are bone-resorbing multinuclear cells derived from hematopoietic stem cells which are specialised to carry out lacunar bone resorption. The immunophenotype of giant cell-containing bone lesions in a wide range of osteoclast-like giant cells was similarly assessed. Both multinucleated macrophages and osteoclasts were found to express CD68. Multinucleated macrophages, but not osteoclasts, expressed GrB and Ki67. CD13+/CD14+/CD68+/GrB-/Ki67-/CD56- all giant-cell lesions noted in giant cells of bone. Giant cells have an osteoclast phenotype in most giant cell-rich lesions of bone, which do not express the macrophage-associated antigens GrB and Ki67. Our results indicate that they are formed from osteoclast precursors of mononuclear phagocyte.