The association between frailty and osteoarthritis based on the NHANES and Mendelian randomization study.

Introduction: The aim of the study was to examine the association between frailty and osteoarthritis. Methods: We conducted a cross-sectional study in the National Health and Nutrition Examination Survey, while logistic regression was used to explore the association of the two. Mendelian randomization (MR) study was used to explore the causal relationship between the two. Results: In the cross-sectional study, logistic regression analysis showed that odds ratio (OR) (95% CI) value was 1.07 (1.05, 1.08). In the MR study, the inverse-variance weighting (IVW) results showed OR (95% CI) value of 1.69 (1.01-2.83). Conclusions: There is both a correlation and a causal relationship between frailty and osteoarthritis, and frailty may be a potentially better response than age to osteoarthritis.

A comprehensive analysis of systematically screened laboratory tests: based on a COVID-19 cohort.

INTRODUCTION: The study aimed at screening indicators with differential diagnosis values and investigating the characteristics of laboratory tests in COVID-19 patients. METHODOLOGY: All the laboratory tests from COVID-19 patients and non-COVID-19 patients in this cohort were included. Test values from the groups during the course, days 1-7, and days 8-14 were analyzed. Mann-Whitney U test, univariate logistic regression analysis, and multivariate regression analysis were performed. Regression models were established to verify the diagnostic performance of indicators. RESULTS: 302 laboratory tests were included in this cohort, and 115 indicators were analyzed; the values of 61 indicators had significant differences (p < 0.05) between groups, and 23 indicators were independent risk factors of COVID-19. During days 1-7, the values of 40 indicators had significant differences (p < 0.05) between groups, while 20 indicators were independent risk factors of COVID-19. During days 8-14, the values of 45 indicators had significant differences (p < 0.05) between groups, and 23 indicators were independent risk factors of COVID-19. About 10, 12, and 12 indicators showed significant differences (p < 0.05) in multivariate regression analysis in different courses respectively, and the diagnostic performance of the model from them was 74.9%, 80.3%, and 80.8% separately. CONCLUSIONS: The indicators obtained through systematic screening have preferable differential diagnosis values. Compared with non-COVID-19 patients, the screened indicators indicated that COVID-19 patients had more severe inflammatory responses, organ damage, electrolyte and metabolism disturbance, and coagulation disorders. This screening approach could find valuable indicators from a large number of laboratory test indicators.

A quantitative exploration of symptoms in COVID-19 patients: an observational cohort study.

Background: As the spreading of the COVID-19 around the global, we investigated the characteristics and changes of symptoms in COVID-19 patients. Methods: This was an ambispective observational cohort study, and 133 confirmed COVID-19 patients were included and all symptoms over the course were analyzed qualitatively. The symptoms, their changes over the course in the cohort and in the different clinical types, etc. were illustrated. Differences in different periods and severities were analyzed through Chi square test, association with severity was analyzed through LASSO binomial logistic regression analysis. Inter-correlation and classification of symptoms were completed. Major symptoms were screened and their changes were illustrated. Results: A total of 43 symptoms with frequencies as 6067 in this cohort. Differences of symptoms in different stages and clinical types were significant. Expectoration, shortness of breath, dyspnea, diarrhea, poor appetite were positively but vomiting, waist discomfort, pharyngeal discomfort, acid reflux were negatively correlated with the combined-severe and critical type; dyspnea was correlated with the critical type. The 17 major symptoms were identified. The average daily frequency of symptoms per case was decreased continuously before the transition into the severe type and increased immediately one day before the transition and then decreased. It was decreased continuously before the transition date of the critical type and increased from the transition into the critical type to the next day and decreased thereafter. Dyspnea (P<0.001), shortness of breath (P<0.01) and chest distress (P<0.05) were correlated with death and their corresponding coefficient was 0.393, 0.258, 0.214, respectively. Conclusion: The symptoms of COVID-19 patients mainly related to upper respiratory tract infection, cardiopulmonary function, and digestive system. The mild type and the early stage in other types mainly related to upper respiratory tract infection. The cardiopulmonary function and digestive system associated symptoms were found in all other types and stages. Dyspnea was correlated with critical type, and dyspnea, shortness of breath and chest distress were correlated with death. Respiratory dysfunction (or incompleteness) associated symptoms were the characteristic symptoms. The changes of symptoms did not synchronously with the changes of severity before the transition into the severe or critical type.

Hypoxic Preconditioning Enhances the Efficacy of Mesenchymal Stem Cells-Derived Conditioned Medium in Switching Microglia toward Anti-inflammatory Polarization in Ischemia/Reperfusion.

Activation of pro-inflammatory microglia is an important mechanism of the cerebral ischemia-reperfusion (I/R)-induced neuronal injury and dysfunction. Mesenchymal stem cells (MSCs) together with their paracrine factors demonstrated curative potential in immune disorders and inflammatory diseases, as well as in ischemic diseases. However, it remains unclear whether conditioned medium from MSCs could effectively regulate the activation and polarization of microglia exposed to I/R stimulation. In this study, we investigated the effects of conditioned medium from bone marrow MSCs (BMSCs-CM) on I/R-stimulated microglia and the potential mechanism involved, as well as the way to obtain more effective BMSCs-CM. First, cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) was established in microglia to mimic the I/R. BMSCs-CM from different culture conditions (normoxic: 21% O2; hypoxic: 1% O2; hypoxia preconditioning: preconditioning with 1% O2 for 24 h) was used to treat the microglia. Our results showed that BMSCs-CM effectively promoted the survival and alleviated the injury of microglia. Moreover, in microglia exposed to OGD/R, BMSCs-CM inhibited significantly the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), CD86 and inducible nitric oxide synthase, whereas upregulated the levels of anti-inflammatory cytokine (IL-10), CD206 and Arginase-1. These results suggested that BMSCs-CM promoted the polarization of anti-inflammatory microglia. In particular, BMSCs-CM from cultures with hypoxia preconditioning was more effective in alleviating cell injury and promoting anti-inflammatory microglia polarization than BMSCs-CM from normoxic cultures and from hypoxic cultures. Furthermore, inhibition of exosomes secretion could largely mitigate these effects of BMSCs-CM. In conclusion, our results suggested that hypoxia preconditioning of BMSCs could enhance the efficacy of BMSCs-CM in alleviating OGD/R-induced injury and in promoting the anti-inflammatory polarization of microglia, and these beneficial effects of BMSCs-CM owed substantially to exosomes.

Features of α-HBDH in COVID-19 patients: A cohort study.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has spread all over the world and brought extremely huge losses. At present, there is a lack of study to systematically analyze the features of hydroxybutyrate dehydrogenase (α-HBDH) in COVID-19 patients. METHODS: Electronic medical records including demographics, clinical manifestation, α-HBDH results and outcomes of all included patients were extracted. RESULTS: α-HBDH in COVID-19 group was higher than that in excluded group (p < 0.001), and there was no significant difference in α-HBDH before and after the exclusion of 5 patients with comorbidity in heart or kidney (p = 0.671). In COVID-19 group, the α-HBDH value in ≥61 years old group, severe group, and critical group, death group all increased at first and then decreased, while no obvious changes were observed in other groups. And there were significant differences of the α-HBDH value among different age groups (p < 0.001), clinical type groups (p < 0.001), and outcome groups (p < 0.001). The optimal scale regression model showed that α-HBDH value (p < 0.001) and age (p < 0.001) were related to clinical type. CONCLUSIONS: α-HBDH was increased in COVID-19 patients, obviously in ≥61 years old, death and critical group, indicating that patients in these three groups suffer from more serious heart and kidney and other tissues and organs damage, higher α-HBDH value, and risk of death. The difference between death and survival group in early stage might provide a approach to judge the prognosis. The accuracy of the model to distinguish severe/critical type and other types was 85.84%, suggesting that α-HBDH could judge the clinical type accurately.

Bone marrow mesenchymal stem cells-derived conditioned medium protects cardiomyocytes from hypoxia/reoxygenation-induced injury through Notch2/mTOR/autophagy signaling.

Bone marrow mesenchymal stem cells (BMSC) can ameliorate ischemic injury of various tissues. However, the molecular mechanisms involved remain to be clarified. In this study, we intend to investigate the effects of BMSC-derived conditioned medium (BMSC-CM) on hypoxia/reoxygenation (H/R)-induced injury of H9c2 myocardial cells, and the potential mechanisms. Cell injury was determined through level of cell viability, lactate dehydrogenase (LDH) release, total intracellular reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), and cell apoptosis. Autophagic activity of cells was detected through levels of the autophagy-associated proteins and autophagic flux. Results showed that BMSC-CM alleviated H/R-induced injury in H9c2 cells, as demonstrated by increased cell viability and Δψm, decreased ROS production, LDH release, and cell apoptosis. Furthermore, the H/R treatment induced a decrease in autophagic activity and an increase in Notch2 signaling activation in H9c2 cells. In the presence of BMSC-CM, the autophagic activity impaired by the H/R treatment was upregulated with decreased phosphorylation of mTOR, and the activation of Notch2 signaling was downregulated. These effects of BMSC-CM could be replicated by Notch signaling inhibitor. In contrast, inhibitors of cell autophagy including chloroquine (CQ) and 3-methyladenine, diminished the protective effects of BMSC-CM. Taken together results, our study showed that BMSC-CM could protect H9c2 cells from H/R-induced injury potentially through regulating Notch2/mTOR/autophagy signaling. These findings may provide a novel insight into the mechanisms of BMSC-CM in therapy of myocardial ischemia/reperfusion injury as well as other ischemic diseases.