Identification of novel biomarkers for frailty diagnosis via serum amino acids metabolomic analysis using UPLC-MS/MS.

PURPOSE: This study was aimed to analyze serum amino acid metabolite profiles in frailty patients, gain a better understanding of the metabolic mechanisms in frailty, and assess the diagnostic value of metabolomics-based biomarkers of frailty. EXPERIMENTAL DESIGN: This study utilized the ultra-performance liquid chromatography tandem mass spectrometry to examine amino acids associated with frailty. Additionally, we employed multivariate statistical methods, metabolomic data analysis, receiver operating characteristic (ROC) curve analysis, and pathway enrichment analysis. RESULTS: Among the assayed amino acid metabolites, we identified biomarkers for frailty. ROC curve analysis for frailty diagnosis based on the modified Fried's frailty index showed that the areas under ROC curve of tryptophan, phenylalanine, aspartic acid, and combination were 0.775, 0.679, 0.667, and 0.807, respectively. ROC curve analysis for frailty diagnosis based on Frail Scale showed that the areas under ROC curve of cystine, phenylalanine, and combination of amino acids (cystine, L-Glutamine, citrulline, tyrosine, kynurenine, phenylalanine, glutamin acid) were 0.834, 0.708, and 0.854 respectively. CONCLUSION AND CLINICAL RELEVANCE: In this study, we explored the serum amino acid metabolite profiles in frailty patients. These present metabolic analyses may provide valuable information on the potential biomarkers and the possible pathogenic mechanisms of frailty. CLINICAL SIGNIFICANCE: Frailty is a clinical syndrome, as a consequence it is challenging to identify at early course of the disease, even based on the existing frailty scales. Early diagnosis and appropriate patient management are the key to improve the survival and limit disabilities in frailty patients. Proven by the extensive laboratory and clinical studies on frailty, comprehensive analysis of metabolic levels in frail patients, identification of biomarkers and study of pathogenic pathways of metabolites contribute to the prediction and early diagnosis of frailty. In this study, we explored the serum amino acid metabolite profiles in frailty patients. These present metabolic analyses may provide valuable information on the potential biomarkers and the possible pathogenic mechanisms of frailty.

A comparative study of virus nucleic acid re-positive and non-re-positive patients infected with SARS-CoV-2 Delta variant strain in the Ningxia Hui Autonomous Region.

Objective: This study aimed to provide a basis for epidemic prevention and control measures as well as the management of re-positive personnel by analyzing and summarizing the characteristics of re-positive patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infections discharged from a hospital in the Ningxia Hui Autonomous Region in 2021. Methods: This case-control study included a total of 45 patients with Delta variant infections diagnosed in the Fourth People's Hospital of the Ningxia Hui Autonomous Region between October 17 and November 28, 2021. Based on the nucleic acid test results post-discharge, the patients were dichotomized into re-positive and non-re-positive groups. Based on the time of the first re-positive test, the re-positive group was further divided into <7 and ≥7 days groups to compare their clinical characteristics and explore the possible influencing factors of this re-positivity. Results: Of the 45 total patients, 16 were re-positive (re-positivity rate: 35.6%), including four patients who were re-positive after 2 weeks (re-positivity rate: 8.8%). The median time of the first re-positive after discharge was 7 days (IQR: 14-3). The re-positive group was younger than the non-re-positive group (35 vs. 53, P < 0.05), had a higher proportion of patients who were not receiving antiviral therapy (56.2 vs. 17.2%, P < 0.05). The median CT value of nucleic acid in the re-positive group was considerably greater than that at admission (36.7 vs. 22.6 P < 0.05). The findings demonstrated that neutralizing antibody treatment significantly raised the average IgG antibody level in patients, particularly in those who had not received COVID-19 vaccine (P < 0.05). The median lowest nucleic acid CT value of the ≥7 days group during the re-positive period and the immunoglobulin G (IgG) antibody level at discharge were lower than those in the <7 days group (P < 0.05). When compared to the non-positive group, patients in the ≥7 days group had a higher median virus nucleic acid CT value (27.1 vs. 19.2, P < 0.05) and absolute number of lymphocytes at admission (1,360 vs. 952, P < 0.05), and a lower IgG antibody level at discharge (P < 0.05). Conclusions: In conclusion, this study found that: (1) The re-positivity rate of SARS-CoV-2 Delta variant infection in this group was 35.6%, while the re-positivity rate was the same as that of the original strain 2 weeks after discharge (8.0%). (2) Young people, patients who did not use antiviral therapy or had low IgG antibody levels at discharge were more likely to have re-positive. And the CT value of nucleic acid at the time of initial infection was higher in re-positive group. We speculated that the higher the CT value of nucleic acid at the time of initial infection, the longer the intermittent shedding time of the virus. (3) Re-positive patients were asymptomatic. The median CT value of nucleic acid was > 35 at the re-positive time, and the close contacts were not detected as positive. The overall transmission risk of re-positive patients is low.

Outpatient strategies and the changing SARS-CoV-2 epidemic.

In response to the early outbreak of SARS-CoV-2, online fever clinics were set up. Then, an online face-to-face consultation was developed to solve the extreme difficulty of getting medical services to patients with chronic diseases. http://bit.ly/3cPppai.

Association between motoric cognitive risk syndrome and frailty among older Chinese adults.

BACKGROUND: Motoric cognitive risk syndrome (MCR) is a newly proposed predementia syndrome incorporating subjective cognitive complaints and slow gait. Previous studies have reported that subjective cognitive complaints and slow gait are associated with frailty in cognitively unimpaired older adults, but little is known about the link between MCR and frailty in older adults. Therefore, the aim of the study was to explore the associations of MCR and its components with frailty in older Chinese adults. METHODS: In an observational cross-sectional study, a total of 429 older adults aged 60 years and older were admitted to the geriatric department. According to MCR criteria, all participants were classified into 4 groups: 1) the MCR group; 2) the subjective cognitive complaints only group; 3) the slow gait only group; and 4) the healthy control group. Physical frailty was assessed by the Clinical Frailty Scale (CFS). Multivariate logistic regression analysis was used to examine the association between MCR and frailty in older adults. RESULTS: The prevalence rates of subjective cognitive complaints, slow gait and MCR were 15.9, 10.0 and 4.0%, respectively. After adjusting for confounding variables, the logistic regression analysis showed that slow gait (odds ratio [OR]: 3.40, 95% confidence interval [CI]: 1.40-8.23, P = 0.007) and MCR (OR: 5.53, 95% CI: 1.46-20.89, P = 0.012) were independently associated with frailty, but subjective cognitive complaints were not. CONCLUSIONS: MCR and slow gait were significantly associated with frailty in older Chinese adults. Further studies should prospectively determine the causal relationship between MCR and frailty.

Clinical characteristics of 54 medical staff with COVID-19: A retrospective study in a single center in Wuhan, China.

In December 2019, an outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection occurred in Wuhan, and rapidly spread to worldwide, which has attracted many people's concerns about the patients. However, studies on the infection status of medical personnel is still lacking. A total of 54 cases of SARS-Cov-2 infected medical staff from Tongji Hospital between 7 January and 11 February 2020 were analyzed in this retrospective study. Clinical and epidemiological characteristics were compared between different groups by statistical method. From 7 January to 11 February 2020, 54 medical staff of Tongji Hospital were hospitalized due to coronavirus disease 2019 (COVID-19). Most of them were from other clinical departments (72.2%) rather than emergency department (3.7%) or medical technology departments (18.5%). Among the 54 patients with COVID-19, the distribution of age had a significant difference between non-severe type and severe/critical cases (median age: 47 years vs 38 years; P = .0015). However, there was no statistical difference in terms of gender distribution and the first symptoms between theses two groups. Furthermore, we observed that the lesion regions in SARS-Cov-2 infected lungs with severe-/critical-type of medical staff were more likely to exhibit lesions in the right upper lobe (31.7% vs 0%; P = .028) and right lung (61% vs 18.2%; P = .012). Based on our findings with medical staff infection data, we suggest training for all hospital staff to prevent infection and preparation of sufficient protection and disinfection materials.

Viral Infection Increases the Risk of Idiopathic Pulmonary Fibrosis: A Meta-Analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with a poor prognosis. Although many factors have been identified that possibly trigger or aggravate IPF, such as viral infection, the exact cause of IPF remains unclear. Until now, there has been no systematic review to assess the role of viral infection in IPF quantitatively. OBJECTIVE: This meta-analysis aims to present a collective view on the relationship between viral infection and IPF. METHODS: We searched studies reporting the effect of viral infection on IPF in the PubMed, Embase, Cochrane Library, Web of Science, and Wiley Online Library databases. We calculated ORs with 95% CIs to assess the risk of virus in IPF. We also estimated statistical heterogeneity by using I2 and Cochran Q tests and publication bias by using the funnel plot, Begg test, Egger test, and trim-and-fill methods. Regression, sensitivity, and subgroup analyses were performed to assess the effects of confounding factors, such as sex and age. RESULTS: We analyzed 20 case-control studies from 10 countries with 1,287 participants. The pooled OR of all viruses indicated that viral infection could increase the risk of IPF significantly (OR, 3.48; 95% CI, 1.61-7.52; P = .001), but not that of exacerbation of IPF (OR, 0.99; 95% CI, 0.47-2.12; P = .988). All analyzed viruses, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 7 (HHV-7), and human herpesvirus 8 (HHV-8), were associated with a significant elevation in the risk of IPF, except human herpesvirus 6 (HHV-6). CONCLUSIONS: The presence of persistent or chronic, but not acute, viral infections, including EBV, CMV, HHV-7, and HHV-8, significantly increases the risk of developing IPF, but not exacerbation of IPF. These findings imply that viral infection could be a potential risk factor for IPF.

Better approach for autoimmune pulmonary alveolar proteinosis treatment: inhaled or subcutaneous granulocyte-macrophage colony-stimulating factor: a meta-analyses.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare pulmonary disease caused by functional deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF therapy in aPAP has been reported effective in some studies. This meta-analyses aimed to evaluate whether GM-CSF therapy, including inhaled and subcutaneous GM-CSF have therapeutic effect in aPAP patients. METHODS: We analyzed 10 studies searched from PubMed, EmBase, Web of Science, Wiley Online Library and Cochrane Collaboration databases to evaluate the pooled effects of GM-CSF treatment in aPAP patients. RESULTS: Ten observational studies involving 115 aPAP patients were included. The pooled analyses of response rate (81%, p < 0.001), relapse rate (22%, p = 0.009), PaO2 (13.76 mmHg, p < 0.001) and P(A-a)O2 (19.44 mmHg, p < 0.001) showed that GM-CSF treatment was effective on aPAP patients. Further analyses showed that inhaled GM-CSF treatment was more effective than subcutaneous GM-CSF therapy, including a higher response rate (89% vs. 71%, p = 0.023), more improvements in PaO2 (21.02 mmHg vs. 8.28 mmHg, p < 0.001) and P(A-a)O2 (19.63 mmHg vs. 9.15 mmHg, p < 0.001). CONCLUSIONS: As two routes of exogenous GM-CSF treatment, inhaled and subcutaneous were both proven to have effect on aPAP patients. Furthermore, inhaled GM-CSF therapy showed a higher response rate, more improvements on PaO2 and P(A-a)O2 than subcutaneous GM-CSF treatment in aPAP patients, suggesting inhaled GM-CSF therapy could have more benefits on aPAP patients. Therefore, GM-CSF therapy, especially inhaled GM-CSF, might be a promising therapeutic option in treating aPAP.

Multiple diabetic complications, as well as impaired physical and mental function, are associated with declining balance function in older persons with diabetes mellitus.

OBJECTIVE: To investigate whether there is a difference in balance function between older persons with and without diabetes mellitus (DM), and to identify whether mediating factors, such as diabetic complications, Instrumental Activities of Daily Living (IADL) score, Mini-Mental State Examination (MMSE) score, as well as hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL), are associated with balance function in older persons with DM. METHODS: In this cross-sectional study, a total of 208 older persons were divided into a DM group (n=80) and a control group who did not have DM (n=128). Balance function was evaluated with the Tinetti performance-oriented mobility assessment (POMA), which includes balance and gait subscales. Activities of daily living (ADL), IADL, and the MMSE were also measured. Fall incidents in last 12 months, the use of walking aids, fear of falling, comorbidities, and polypharmacy were recorded. Diabetic complications were recorded, and HbA1c, FPG, TC, TG, and LDL were measured in the patients of the DM group. RESULTS: Fall incidents in last 12 months were higher in the DM group than in the control group (P<0.01). POMA score as well as ADL and IADL scores were lower in the diabetic group than the control group (P<0.05). Within the diabetic group, the POMA score was positively related to the ADL score (odds ratio [OR], 11.7; 95% confidence interval [CI], 3.076-44.497; P<0.01), IADL score (OR, 16.286; 95% CI, 4.793-55.333; P<0.01), and MMSE score (OR, 10.524; 95% CI, 2.764-40.074; P<0.01), but was negatively related to age (OR, 7.707; 95% CI, 2.035-29.185; P<0.01) and diabetic complication (OR, 6.667; 95% CI, 2.279-19.504; P<0.01). Also, within the DM group, the decreased POMA score was associated with multiple diabetic complications (OR, 5.977; 95% CI, 1.378-25.926; P<0.05), decreased IADL score (OR, 10.288; 95% CI, 2.410-43.915; P<0.01), and MMSE score (OR, 13.757; 95% CI, 2.556-74.048; P<0.01). CONCLUSION: Multiple diabetic complications, lower MMSE, ADL, and IADL scores were associated with declining balance function in the older persons with DM. These findings can alert physicians to detect and intervene earlier on declining balance in older persons with DM.

Effects of a nutrition plus exercise programme on physical function in sarcopenic obese elderly people: study protocol for a randomised controlled trial.

INTRODUCTION: With a rapidly ageing population, sarcopenic obesity, defined as decreased muscle mass and function combined with increased body fat, is a complex health problem. Although sarcopenic obesity contributes to a decline in physical function and exacerbates frailty in older adults, evidence from clinical trials about the effect of exercise and nutrition on this complex syndrome in Chinese older adults is lacking. METHODS AND ANALYSIS: We devised a study protocol for a single-blind randomised controlled trial. Sarcopenia is described as age-related decline in muscle mass plus low muscle strength and/or low physical performance. Obesity is defined as a percentage of body fat above the 60th centile. Ninety-two eligible participants will be randomly assigned to a control group, nutrition group, exercise group and nutrition plus exercise group to receive an 8-week intervention and 12-week follow-up. The primary outcomes will be the change in short physical performance battery scores, grip strength and 6 m usual gait speed. The secondary outcomes will include basic activities of daily living scores, instrumental activity daily living scores, body composition and body anthropometric indexes. For all main analyses, the principle of intention-to-treat will be used. ETHICS AND DISSEMINATION: This study was approved by the medical ethics committee of Zhejiang Hospital on 25 November 2015. The study will present data targeting the clinical effects of nutrition and exercise on physical function and body composition in a Chinese older population with sarcopenic obesity. The results will help to provide important clinical evidence of the role of complex non-pharmaceutical interventions for sarcopenic obese older people. The findings of this study will be submitted to peer-reviewed medical journals for publication and presented at relevant academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-15007501; Pre-results.

Relationship of serum vitamin D level on geriatric syndromes and physical performance impairment in elderly hypertensive patients.

OBJECTIVE: To investigate the relationship among serum vitamin D levels, physical performance impairment, and geriatric syndromes in elders with hypertension. METHODS: According to the concentration of vitamin D levels, a total of 143 elderly patients with hypertension were classified into vitamin D deficient group (vitamin D ≤ 20 ng/mL, n = 94) and vitamin D appropriate group (vitamin D > 20 ng/mL, n = 49). Geriatric syndromes and physical performance were assessed by using comprehensive geriatric assessment (CGA). Correlation among vitamin D levels, geriatric syndromes and physical performance was analyzed. RESULTS: No statistical differences were found in various aspects of geriatric syndromes between the two groups (P > 0.05). While correlation analysis indicated that vitamin D levels had a positive association with ADL score (r = 0.235, P < 0.01) and a negative association with Morse fall scale score (r = -0.238, P < 0.01). Patients with deficient vitamin D level had longer time both in the Five Time Sit to Stand Test (5tSTS), (15.765 ± 5.593) and the four-meter walk test [7.440 (5.620, 9.200)], a weaker hand-grip in the grip strength test (28.049 ± 9.522), and a lower Tinetti performance-oriented mobility assessment (Tinetti POMA) [26 (22, 27)] and Balance subscale of the Tinetti performance-oriented mobility assessment (B-POMA) score [14 (12, 16)], compared with appropriate vitamin D level [(13.275 ± 3.692); 5.810 (4.728, 7.325)]; (31.989 ± 10.217); [26.5 (25, 28)]; [15 (14, 16), respectively, all P < 0.05]. Furthermore, results of logistic regression indicated that vitamin D was significantly associated with 5tSTS (OR = 1.2, 95% CI = 1.050-1.331, P < 0.01), Tinetti POMA (OR = 3.7, 95% CI:1.284-10.830, P < 0.05) and B-POMA (OR = 0.8, 95% CI:0.643-0.973, P < 0.05). CONCLUSIONS: In elderly hypertensive patients, serum vitamin D deficient level is associated with physical performance impairment. However, no statistical significance was found between vitamin D and geriatric syndromes. Further study is required to investigate possible mechanisms for the association between vitamin D and physical performance.

Protein phosphatase 4 (PP4) functions as a critical regulator in tumor necrosis factor (TNF)-α-induced hepatic insulin resistance.

Protein phosphatase 4 (PP4) was shown to participate in multiple cellular processes, including DNA damage response, cell cycle and embryo development. Recent studies demonstrated a looming role of PP4 in glucose metabolism. However, whether PP4 is involved in hepatic insulin resistance remains poorly understood. The objective of this study was to estimate the role of PP4 in tumor necrosis factor (TNF)-α-induced hepatic insulin resistance. db/db mice and TNF-α-treated C57BL/6J mice were used as hepatic insulin resistance animal models. In vitro models were established in both HepG2 cells and primary hepatocytes by TNF-α treatment. We found that increased expression and activity of PP4 occurred in the livers of db/db mice and TNF-α-induced hepatic insulin resistance both in vitro and in vivo. Actually, PP4 silencing and suppression of PP4 activity ameliorated TNF-α-induced hepatic insulin resistance, whereas over-expression of PP4 caused insulin resistance. We then further investigated the prodiabetic mechanism of PP4 in TNF-α-induced insulin resistance. We found that PP4 formed a complex with IRS-1 to promote phosphorylation of IRS-1 on serine 307 via JNK activation and reduce the expression of IRS-1. Thus, PP4 is an important regulator in inflammatory related insulin resistance.

Uncontrolled hypertension and orthostatic hypotension in relation to standing balance in elderly hypertensive patients.

OBJECTIVE: To investigate the associations among uncontrolled hypertension, orthostatic hypotension (OH), and standing balance impairment in the elderly hypertensive patients referred to comprehensive geriatric assessment (CGA). METHODS: In a cross-sectional study, a total of 176 elderly hypertensive patients who underwent CGA were divided into OH group (n=36) and non-OH group (n=140) according to blood pressure measurement in the supine position, after immediate standing up, and after 1 minute and 3 minutes of standing position. Uncontrolled hypertension was defined as blood pressure of ≥140/90 mmHg if accompanied by diabetes mellitus (DM) or chronic kidney disease (CKD), or ≥150/90 mmHg if no DM and no CKD. Standing balance, including immediate standing balance and prolonged standing balance, was assessed in side-by-side and tandem stance. RESULTS: Neither uncontrolled hypertension nor OH was associated with prolonged standing balance impairment in elderly hypertensive patients (P>0.05). Blood pressure decrease after postural change was significantly associated with immediate standing balance impairment in side-by-side and tandem stance (P<0.05). Patients with OH were at greater risk of immediate standing balance impairment in both side-by-side and tandem stance than those without OH (odds ratio [OR] 3.44, 95% confidence interval [CI] 1.26-9.33, P<0.05; OR 3.14, 95% CI 1.14-8.64, P<0.01). Furthermore, uncontrolled hypertension was associated with immediate standing balance impairment in side-by-side stance (OR 2.96, 95% CI 1.31-6.68, P<0.05). CONCLUSION: Uncontrolled hypertension, OH, and blood pressure decrease after postural change were associated with immediate standing balance impairment, and therefore, a better understanding of the underlying associations might have major clinical value.

A poor performance in comprehensive geriatric assessment is associated with increased fall risk in elders with hypertension: a cross-sectional study.

BACKGROUND: Fall and serious fall injuries have become a major health concern for elders. Many factors including blood pressure and anti-hypertensive medication application were reported as hazards of fall. The purpose of this study was to determine if age related systemic functional decline related with increased fall risks in elderly patients with hypertension. METHODS: A total of 342 elderly hypertension patients (age 79.5 ± 6.7 years, male 63.8%) were recruited to the study. Comprehensive geriatric assessment (CGA), including measurements about activity of daily living (ADL), nutrition, cognition, depression, numbers of prescription medication and number of clinical diagnosis, was conducted to evaluate the physical and mental status of each participants. Fall risk was evaluated by Morse fall scale, Tinetti performance oriented mobility assessment (POMA) and history of fall in the recent year. Participants were grouped into tertiles according to CGA score. Correlation between CGA and fall risk was analyzed through SPSS 18.0. RESULTS: Participants with higher CGA score were likely to be older, had a lower body mass index (BMI), and a higher prevalence of cardiovascular disease, chronic obstructive pulmonary disease (COPD), cerebrovascular disease and osteoarthropathia. Participants in higher tertile of CGA score got increased prevalence of fall risk than those in lower tertile (P < 0.01 T3 vs. T1, P < 0.01 T3 vs. T2). Correlation analysis and regression analysis showed significant association between CGA and Morse fall scale (P < 0.001), as well as CGA and POMA (P < 0.001). Meanwhile, CGA components also showed co-relationships with increase fall risks. After adjusting age, BMI, benzodiazepine use, cardiovascular disease, cerebrovascular disease, COPD and osteoarthropathia, both history of fall in the recent year and rising Morse fall scale were significantly associated with ADL impairment (OR: 2.748, 95%CI: 1.598-4.725), (OR: 3.310, 95%CI: 1.893-5.788). Decreased Tinetti POMA score was associated with Mini-Mental State Examination (MMSE) (OR: 4.035, 95%CI: 2.100-7.751), ADL (OR: 2.380, 95%CI: 1.357-4.175) and shortened MNA form (MNA-SF) impairment (OR: 2.692, 95%CI: 1.147-6.319). CONCLUSIONS: In elderly adults with hypertension, impaired physical and mental function is associated with increased fall risk. Further study is required to investigate possible mediators for the association and effective interventions.

Apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ.

Apelin, a novel adipokine, is the specific endogenous ligand of G protein-coupled receptor APJ. Consistent with its putative role as an adipokine, apelin has been linked to states of insulin resistance. However, the function of apelin in hepatic insulin resistance, a vital part of insulin resistance, and its underlying mechanisms still remains unclear. Here we define the impacts of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes. Our studies indicate that apelin reversed TNF-α-induced reduction of glycogen synthesis in HepG2 cells, mouse primary hepatocytes and liver tissues of C57BL/6J mice by improving JNK-IRS1-AKT-GSK pathway. Moreover, Western blot revealed that APJ, but not apelin, expressed in the hepatocytes and liver tissues of mice. We found that F13A, a competitive antagonist for G protein-coupled receptor APJ, suppressed the effects of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes, suggesting APJ is involved in the function of apelin. In conclusion, we show novel evidence suggesting that apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ. Apelin appears as a beneficial adipokine with anti-insulin resistance properties, and thus as a promising therapeutic target in metabolic disorders.