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Background: Cholesterol (CHO) is an essential component of the body. However, high CHO levels in the body can damage bone mass and promote osteoporosis. CHO accumulation can cause osteoblast apoptosis, which has a negative effect on bone formation. The pathogenesis of osteoporosis is a complicate process that includes oxidative stress, endoplasmic reticulum (ER) stress, and inflammation. Geniposide (GEN) is a natural compound with anti-osteoporotic effect. However, the roles of GEN in osteopathogenesis are still unclear. Our previous studies demonstrated that GEN could reduce the accumulation of CHO in osteoblasts and the activation of ER stress in osteoblasts. However, the molecular mechanism of GEN in inhibiting CHO-induced apoptosis in osteoblasts needs to be further investigated. Methods: MC3T3-E1 cells were treated with osteogenic induction medium (OIM). Ethanol-solubilized cholesterol (100 µM) was used as a stimulator, and 10 µM and 25 µM geniposide was added for treatment. The alterations of protein expression were detected by western blot, and the cell apoptosis was analyzed by a flow cytometer. Results: CHO promoted osteoblast apoptosis by activating ER stress in osteoblasts, while GEN alleviated the activation of ER stress and reduced osteoblast apoptosis by activating the GLP-1R/ABCA1 pathway. Inhibition of ABCA1 or GLP-1R could eliminate the protective activity of GEN against CHO-induced ER stress and osteoblast apoptosis. Conclusion: GEN alleviated CHO-induced ER stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin glycation index (HGI), which is calculated by blood glucose and hemoglobin A1c(HbA1c), reflects the individual discrepancy in HbA1c. This study aimed to investigate the association between HGI/HbA1c and serum uric acid(SUA) stratified by sex and diabetes. Methods: The study recruited 33772 participants who underwent physical examinations between April 2016 and August 2021 in Beijing Chao-Yang Hospital. A random subsample of 3000 subjects was utilized to calculate the formula of HGI and data of the remaining 30772 participants were used for analysis. HGI and HbA1c were categorized according to quartiles (Q1, Q2, Q3, Q4), using Q1 as the reference. We used multiple linear regression and restricted cubic splines for data analysis. Results: 30772 participants with a mean age of 44.4 years old were included in the analysis, 48.6% (N = 14944) of which were female and 7.7% (N = 2363) with diabetes. Associations of HGI, HbA1c and SUA were modified by sex and diabetes. The relationship between SUA levels and HGI was positive in women without diabetes, with one unit increase in HGI associating with an 11.3 μmol/L increase in SUA (P < 0.001) after adjusting for other confounders. On average, each one-unit increase in HbA1c was associated with a 14.3 μmol/L decrease in SUA in women with diabetes, a 14.9 μmol/L decrease in SUA in men with diabetes, and a 16.5 μmol/L increase in SUA in women without diabetes (all P < 0.001). The SUA levels in men without diabetes showed a bell-shaped relation with HbA1c, increasing as the HbA1c rose to around 5.7% and then falling with a further increase of HbA1c (P < 0.001). Conclusions: SUA levels were inversely correlated with HbA1c in diabetic patients, also in men with prediabetes (HbA1c ≥ 5.7%), but positively correlated with HbA1c and HGI in women without diabetes. Glycemic control may help to reduce the risk of hyperuricemia in non-diabetes women. [ABSTRACT FROM AUTHOR]

Background: The lymphocytes played an important role in the natural history of cancer. The aim of this study was to explore the prognostic value of lymphocyte count and percentage for survival in advanced cancer patients receiving palliative care.Methods: A retrospective review of clinicopathological data from 378 consecutive advanced cancer patients and 106 extended follow-up patients treated with palliative care was conducted. Kaplan-Meier curves and multivariate cox regression analyses were used to evaluate the relationships of peripheral lymphocyte count (LC) and lymphocyte to white blood cell ratio (LWR) with overall survival (OS).Results: The median values for pretreatment LC and LWR were 1.1 (IQR, 0.8 ~ 1.5 × 109/L) and 0.138 (IQR, 0.086 ~ 0.208). The median survival times across LWR quartiles were 19, 47, 79, and 101 days (P < 0.001). Multivariate analysis indicated that patients in the highest quartiles of LC and LWR had an HR of 1.082 (95% CI 0.777 ~ 1.506, P = 0.642) and 0.466 (95% CI 0.328 ~ 0.661, P < 0.001), respectively, compared with patients in the lowest quartiles. Furthermore, only the dynamic changes of LWR were confirmed as an independent prognostic factor for overall survival during the follow-up (HR = 0.396, 95% CI 0.243 ~ 0.668; P = 0.001), as were primary tumor site and ECOG. No effect was observed for the dynamic changes of LC.Conclusions: Our findings demonstrate that measurement of the dynamic changes of LWR prior to treatment and during follow-up may represent a simple and new powerful prognostic factor for patients with advanced cancer, unlike measurement of LC. As a bedside marker of immune status, the prognostic role of LWR should be further evaluated in prospective studies. [ABSTRACT FROM AUTHOR]

Background: According to the current official guidelines, at least 12 lymph nodes (LNs) are qualified as an adequate sampling for colon cancer patients. However, patients evaluated with less nodes were still common in the United States, and the prevalence of positive nodal disease may be under-estimated because of the false-negative assessment. In this study, we present a statistical model that allows preoperative determination of the minimum number of lymph nodes needed to confirm a node-negative disease with certain confidence.Methods: Adenocarcinoma colon cancer patients with stage T1-T3, diagnosed between 2004 and 2013, who did not receive neoadjuvant therapies and had at least one lymph node pathologically examined, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. A beta binomial distribution was used to estimate the probability of an occult nodal disease is truly node-negative as a function of total number of LNs examined and T stage.Results: A total of 125,306 patients met study criteria; and 47,788 of those were node-positive. The probability of falsely identifying a patient as node-negative decreased with an increasing number of nodes examined for each stage, and was estimated to be 72% for T1 and T2 patients with a single node examined and 57% for T3 patients with a single node examined. To confirm an occult nodal disease with 90% confidence, 3, 8, and 24 nodes need to be examined for patients from stage T1, T2, and T3, respectively.Conclusions: The false-negative rate of diagnosed node negative, together with the minimum number of examined nodes for adequate staging, depend preoperatively on the clinical T stage. Predictive tools can recommend a threshold on the minimum number of examined nodes regarding to the favored level of confidence for each T stage. [ABSTRACT FROM AUTHOR]

Background: Little is known about the long-term shifts in distributions of three abdominal-obesity-related indicators, waist circumference (WC), waist-to-hip ratio (WHpR) and waist-to-height ratio (WHtR) among Chinese adults. Traditional mean regression models used in the previous analyses were limited in their ability to capture cross-distribution among effects. The current study aims to describe the shift in distribution of WC, WHpR, and WHtR over a period of 18 years (1993-2011) in China, and to reveal quantile-specific associations of the three indicators with key covariates.Methods: Longitudinal data from seven waves of the China Health and Nutrition Surveys (CHNS) in 1993, 1997, 2000, 2004, 2006, 2009 and 2011 were analyzed. The LMS method was used to illustrate the gender-specific quantile curves of WC, WHtR and WHpR over age. Separate gender-stratified longitudinal quantile regressions were employed to investigate the effect of important factors on the trends of the three indicators.Results: A total of 11,923 participants aged 18-65 years with 49,507 observations were included in the analysis. The density curves of WC, WHtR and WHpR shifted to right and became wider. The three outcomes all increased with age and increased more at upper percentiles. From the multivariate quantile regression, physical activity was negatively associated in both genders; smoking only had a negative effect on male indicators. Education and drinking behavior both had opposite effects on the three indicators between men and women. Marital status and income were positively associated with the shifts in WC, WHtR and WHpR in male and female WC, while urbanicity index had a positive effect on three outcomes in men but inconsistent effect among female outcomes.Conclusions: The abdominal-obesity related indicators of the Chinese adults experienced rapid growth according to our population-based, age- and gender-specific analyses. Over the 18-year study period, major increases in WC, WHtR and WHpR were observed among Chinese adults. Specifically, these increases were greater at upper percentiles and in men. Age, physical activity, energy intake, drinking, smoking, education, income and urbanicity index were associated with elevated abdominal obesity indicators, and the effects differed among percentiles and between genders. [ABSTRACT FROM AUTHOR]

Background: Although palliative care has been accepted throughout the cancer trajectory, accurate survival prediction for advanced cancer patients is still a challenge. The aim of this study is to identify pre-palliative care predictors and develop a prognostic nomogram for overall survival (OS) in mixed advanced cancer patients. Methods: A total of 378 consecutive advanced cancer patients were retrospectively recruited from July 2013 to October 2015 in one palliative care unit in China. Twenty-three clinical and laboratory characters were collected for analysis. Prognostic factors were identified to construct a nomogram in a training cohort (n = 247) and validated in a testing cohort (n = 131) from the setting. Results: The median survival time was 48.0 (95% CI: 38.1–57.9) days for the training cohort and 52.0 (95% CI: 34.6–69.3) days for the validation cohort. Among pre-palliative care factors, sex, age, tumor stage, Karnofsky performance status, neutrophil count, hemoglobin, lactate dehydrogenase, albumin, uric acid, and cystatin-C were identified as independent prognostic factors for OS. Based on the 10 factors, an easily obtained nomogram predicting 90-day probability of mortality was developed. The predictive nomogram had good discrimination and calibration, with a high C-index of 0.76 (95% CI: 0.73–0.80) in the development set. The strong discriminative ability was externally conformed in the validation cohort with a C-index of 0.75. Conclusions: A validated prognostic nomogram has been developed to quantify the risk of mortality for advanced cancer patients undergoing palliative care. This tool may be useful in optimizing therapeutic approaches and preparing for clinical courses individually. [ABSTRACT FROM AUTHOR]

Background: Gold nanoparticles (AuNPs) have been widely studied for biomedical applications, although their safety and potential toxicity in pregnancy remains unknown. The aim of this study is to explore the effect of AuNPs maternal exposure at different gestational ages on fetal survival and development, as well as the potential mechanism of AuNPs affecting embryos and fetuses. Methods: Thirty nm polyethylene glycol (PEG)-coated AuNPs (A30) were administered to pregnant mice via intravenous injection (5 μg Au/g body weight) over three days at either early or late pregnancy. Fetal abortion rate and morphological development in E16.5 were then detected in detail. The pregnant mice physiological states with A30 exposure were examined by biochemical, histological or imaging methods; and materno-fetal distribution of gold elements was assayed by electron microscopy and mass spectrometry. Murine embryonic stem cells derived embryoid-bodies or neuroectodermal cells were treated with A30 (0.0025 to 0.25 μg Au/mL) to examine A30 effects on expression levels of the germ differentiation marker genes. Tukey's method was used for statistical analysis. Results: Exposure to A30 during early (A30E) but not late (A30L) pregnancy caused a high abortion rate (53.5%), lower fetal survival rate and abnormal decidualization compared with non-exposed counterparts. The developmental damage caused by A30 followed an "all-or-nothing" pattern, as the non-aborted fetuses developed normally and pregnancies maintained normal endocrine values. A30 caused minor impairment of liver and kidney function of A30E but not A30L mice. TEM imaging of fetal tissue sections confirmed the transfer of A30 into fetal brain and live as aggregates. qPCR assays showed A30 suppressed the expression of ectodermal, but not mesodermal and endodermal differentiation markers. Conclusions: These results illustrate that maternal A30 exposure in early pregnant results in A30 transfer into embryonic tissues, inhibiting ectodermal differentiation of embryonic stem cells, leading to abnormal embryonic development and abortion. While exposure to A30 during late pregnancy had little or no impact on dams and fetuses. These findings suggest the safety of biomedical applications employing AuNPs during pregnancy is strongly influenced by fetal maturity and gestational age at exposure and provide the clues for AuNPs safe application period in pregnancy. [ABSTRACT FROM AUTHOR]