Application, knowledge and training needs regarding comprehensive geriatric assessment among geriatric practitioners in healthcare institutions: a cross-sectional study.

BACKGROUND: This study aimed to investigate the actual application, knowledge, and training needs of comprehensive geriatric assessment (CGA) among geriatric practitioners in China. METHODS: A total of 225 geriatric practitioners attending the geriatric medicine or geriatric nursing training were recruited for this cross-sectional study. The questionnaire included demographics, healthcare institution characteristics, the actual application, knowledge, training needs, and barriers to CGA and geriatric syndromes (GS). RESULTS: Physicians and nurses were 57.3% and 42.7%, respectively. 71.1% were female, with a median age was 35 years. Almost two-thirds (140/225) of geriatric practitioners reported exposure to CGA in their clinical practice. The top five CGA evaluation items currently used were malnutrition risk (49.8%), fall risk (49.8%), activity of daily living (48.0%), pain (44.4%), and cognitive function (42.7%). Median knowledge scores for the management procedures of GS ranged from 2 to 6. Physicians identified medical insurance payment issues (29.5%) and a lack of systematic specialist knowledge and technology (21.7%) as the two biggest barriers to practicing geriatrics. Nurses cited a lack of systematic specialist knowledge and technology (52.1%) as the primary barrier. In addition, physicians and nurses exhibited significant differences in their knowledge of CGA-specific evaluation items and management procedures for GS (all P < 0.05). However, there were no significant differences in their training needs, except for polypharmacy. CONCLUSIONS: The rate of CGA application at the individual level, as well as the overall knowledge among geriatric practitioners, was not adequate. Geriatric education and continuous training should be tailored to address the specific roles of physicians and nurses, as well as the practical knowledge reserves, barriers, and training needs they face.

Incremental diagnostic value of radiomics signature of pericoronary adipose tissue for detecting functional myocardial ischemia: a multicenter study.

OBJECTIVES: To determine the incremental diagnostic value of radiomics signature of pericoronary adipose tissue (PCAT) in addition to the coronary artery stenosis and plaque characters for detecting hemodynamic significant coronary artery disease (CAD) based on coronary computed tomography angiography (CCTA). METHODS: In a multicenter trial of 262 patients, CCTA and invasive coronary angiography were performed, with fractional flow reserve (FFR) in 306 vessels. A total of 13 conventional quantitative characteristics including plaque characteristics (N = 10) and epicardial adipose tissue characteristics (N = 3) were obtained. A total of 106 radiomics features depicting the phenotype of the PCAT surrounding the lesion were calculated. All data were randomly split into a training dataset (75%) and a testing dataset (25%). Then three models (including the conventional model, the PCAT radiomics model, and the combined model) were established in the training dataset using multivariate logistic regression algorithm based on the conventional quantitative features and the PCAT radiomics features after dimension reduction. RESULTS: A total of 124/306 vessels showed functional ischemia (FFR ≤ 0.80). The radiomics model performed better in discriminating ischemia from non-ischemia than the conventional model in both training (area under the receiver operating characteristic (ROC) curve (AUC): 0.770 vs 0.732, p < 0.05) and testing datasets (AUC: 0.740 vs 0.696, p < 0.05). The combined model showed significantly better discrimination than the conventional model in both training (AUC: 0.810 vs 0.732, p < 0.05) and testing datasets (AUC: 0.809 vs 0.696, p < 0.05). CONCLUSIONS: The PCAT radiomics model showed good performance in predicting myocardial ischemia. Addition of PCAT radiomics to lesion quantitative characteristics improves the predictive power of functionally relevant CAD. KEY POINTS: • Based on the plaque characteristics and EAT characteristics, the conventional model showed poor performance in predicting myocardial ischemia. • The PCAT radiomics model showed good prospect in predicting myocardial ischemia. • When combining the radiomics signature with the conventional quantitative features (including plaque features and EAT features), it showed significantly better performance in predicting myocardial ischemia.

A protocol for randomized controlled trial on multidisciplinary interventions for mobility limitation in the older adults (M-MobiLE).

BACKGROUND: Mobility limitation-the loss of exercise capacity or independent living ability-is a common geriatric syndrome in older adults. As a potentially reversible precursor to disability, mobility limitation is influenced by various factors. Moreover, its complex physiological mechanism hinders good therapeutic outcomes with a single-factor intervention. Most hospitals have not incorporated the diagnosis and evaluation of mobility limitation into medical routines nor developed a multidisciplinary team (MDT) treatment plan. We aim to conduct a clinical trial titled "A Multidisciplinary-team approach for management of Mobility Limitation in Elderly (M-MobiLE)" to explore the effect of the MDT decision-making intervention for mobility limitation. METHODS: The M-MobiLE study will be a multicenter, randomized, and controlled trial. We will recruit a minimum of 66 older inpatients with mobility limitation from at least five hospitals. Older patients with mobility limitation admitted to the geriatrics department will be included. Short-Physical Performance Battery (SPPB), Activities of Daily Living (ADL), Function Impairment Screening Tool (FIST), Geriatric Depression Scale (GDS-15), Short Form - 12 (SF-12), Fried frailty phenotype, social frailty, Morse Fall Risk Scale, SARC-CalF, Mini-Mental State Examination (MMSE), Mini-Nutritional Assessment Short-Form (MNA-SF), and intrinsic capacity will be assessed. The intervention group will receive an exercise-centered individualized MDT treatment, including exercise, educational, nutritional, medical, and comorbidity interventions; the control group will receive standard medical treatment. The primary outcome is the change in the SPPB score, and the secondary outcomes include increased SF-12, ADL, FIST, MMSE, MNA-SF, and intrinsic capacity scores and decreased GDS-15 and SARC-CalF scores. CONCLUSION: Our results will help develop a multidisciplinary decision-making clinical pathway for inpatients with mobility limitation, which can be used to identify patients with mobility limitation more effectively, improve mobility, and reduce the risk of falls, frailty, and death in older inpatients. The implementation of this MDT strategy may standardize the treatment of mobility limitation, reduce adverse prognosis, and improve quality of life. TRIAL REGISTRATION: ChiCTR, ChiCTR2200056756, Registered 19 February 2022.

Preliminary application of three-dimensional printing in congenital uterine anomalies based on three-dimensional transvaginal ultrasonographic data.

BACKGROUND: The three-dimensional (3D) printing technology has remarkable potential as an auxiliary tool for representing anatomical structures, facilitating diagnosis and therapy, and enhancing training and teaching in the medical field. As the most available diagnostic tool and it is routinely used as the first approach in diagnosis of the uterine anomalies, 3D transvaginal ultrasonography (3D-TVS) has been proposed as non-invasive "gold standard" approach for these malformations due to high diagnostic accuracy. Despite holding promise of manufacturing 3D printed models based on 3D-TVS data, relevant reports about 3D-TVS derived gynecological 3D printing haven't been reported to the best of our knowledge. We found an opportunity to explore the feasibility of building 3D printed models for the abnormal uterus based on the data acquired by 3D-TVS. METHODS: The women suspected with congenital uterine anomalies (CUAs) were enrolled in the study. The diagnose of CUAs were made by 3D-TVS scanning and further confirmed under the hysteroscopy examination. One volunteer with normal uterus was enrolled as control. All subjects underwent 3D-TVS scanning for 3D printing data collection. Acquired images were stored and extracted as DICOM files, then processed by professional software to portray and model the boundary of the uterine inner and outer walls separately. After the computer 3D models were constructed, the data were saved and output as STL files for further surface restoration and smoothing. The colors of endometrium and uterine body were specified, respectively, in the print preview mode. Then the uncured photosensitive resin was cleaned and polished to obtain a smooth and transparent solid model after printed models were cooled down. RESULTS: 3D printing models of normal uterus, incomplete septate uterus, complete septate uterus, uterus didelphys and unicornuate uterus were produced on ultrasonographic data of 3D-TVS. CONCLUSIONS: Our research and practice made the first try in modeling CUAs successfully based on ultrasonographic data entirely, verifying that it's a feasible way to build 3D printed models of high-quality through 3D-TVS scanning.

Orthostatic hypotension is associated with malnutrition diagnosed by GLIM in elderly hypertensive patients.

BACKGROUND: Orthostatic Hypotension (OH) and malnutrition, are common health problems in elderly hypertensive patients. This study aimed to analyze the relationship between malnutrition and OH in elderly hypertensive patients. METHODS: This is a cross-sectional single-center study. All participants underwent a Comprehensive Geriatric Assessment (CGA), in which malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM) criteria based on four different methods of diagnosing muscle mass loss. Furthermore, the accuracy of these methods was verified by Receiver Operating Characteristic (ROC) analysis. Univariate and multivariate logistic regression analyses were used to identify risk factors for OH in elderly hypertensive patients. RESULTS: For GLIM criteria, when Fat-Free Mass Index (FFMI) was the gold standard for muscle mass loss, the Area Under ROC Curve (AUC) values for Upper Arm Circumference (UAC), Calf Circumference (CC), and Hand Grip Strength (HGS) were 0.784, 0.805, and 0.832, with moderate accuracy in diagnosing malnutrition. Multivariate analysis showed that females, Diabetes Mellitus (DM), diuretics, and malnutrition diagnosed by GLIM-UAC were risk factors for OH in elderly hypertensive patients. CONCLUSION: Prompt detection of malnutrition in the elderly and attention to changes in UAC may be critical. Similarly, we should strengthen medication and disease management in elderly hypertensive patients.

Associations of poor sleep quality, chronic pain and depressive symptoms with frailty in older patients: is there a sex difference?

BACKGROUND: Sleep disturbance, chronic pain and depressive symptoms later in life are modifiable risk factors and may contribute to frailty. However, much less is known about sex differences in the association between these concurrent symptoms and frailty in older patients. Therefore, we conducted this study to explore the associations of poor sleep quality, chronic pain, and depressive symptoms with frailty in older patients, and the sex-specific associations. METHODS: In an observational population-based study, 540 older hospitalized patients from Zhejiang Hospital in China were enrolled. We collected data on poor sleep quality, pain, depressive symptoms and frailty using the Pittsburgh Sleep Quality Index, the Numerical Rating Scale, the 15-item Geriatric Depression Scale, and the Clinical Frailty Scale. Multivariate logistic regression models were used to explore the total sample and sex-specific associations among symptom burdens, symptom combination patterns and symptom counts, and frailty. RESULTS: After adjusting for the potential covariates, concurrent poor sleep quality and depressive symptoms (OR = 4.02, 95% CI 1.57-10.26), concurrent poor sleep quality and chronic pain (OR = 2.05, 95% CI 1.04-4.05), and having three symptoms (OR = 3.52, 95% CI 1.19-10.44) were associated with a higher likelihood of frailty in older inpatients. In addition, older patients with 2 or 3 symptoms (2 and 3 vs. 0 symptoms) had a higher risk of frailty, and the odds ratios were 2.40 and 3.51, respectively. Interaction analysis and sex-stratified associations exhibited conflicting results. The nonsignificant effect of the interaction of sex and symptoms on frailty, but not the sex-stratified associations, showed that individual symptoms, symptom combination patterns, and symptom counts were associated with elevated risks of frailty in older male patients, but not in older female patients. CONCLUSIONS: Increased symptom burdens were associated with a higher risk of frailty in older inpatients, especially in those with poor sleep quality concurrent with at least one of the other two symptoms. Thus, a multidisciplinary program addressing these common symptoms is required to reduce adverse outcomes.

Impact of Pain and Psychosocial Factors on Frailty Among Older Adults With Physical Functional Limitations: A Cross-Sectional Study.

AIMS: The objective of this study was to determine the prevalence of frailty and pain among older adults with physical functional limitations in China. We also assessed the impact of pain and psychosocial determinants on frailty among this vulnerable population. DESIGN: This study was a cross-sectional study. SETTING AND PARTICIPANTS: Totally, 2,323 Chinese elders with physical functional limitation were enrolled. METHODS: Physical functioning was assessed by the Barthel Index, participants who reported "often troubled with pain" were further asked about the intensity of their pain using a 1-10 numeric rating scale, and frailty was assessed by the Assessment of frailty FRAIL scale. The impact of pain and psychosocial factors on frailty was assessed by multivariable binary logistic regression. RESULTS: The prevalence of frailty and pain were 30.9% and 46.1%, respectively. Compared with subjects who reported no pain, those who reported mild (odds ratio [OR] = 1.70, 95% confidence interval [CI] = 1.21-2.31), moderate (OR = 2.10, 95% CI = 1.53-2.82), or severe pain (OR = 2.31, 95% CI = 1.56-3.40) tended to be more vulnerable to frailty. Furthermore, compared with participants with positive psychosocial determinants, those with negative psychosocial determinants seemed more likely to be frail. CONCLUSIONS: These findings suggest that the incidence of pain, negative psychosocial status, and frailty were prevalent, and the presence of pain and negative psychosocial factors increased the risk of frailty among older adults with physical functional limitation.

The Impact of Intrinsic Capacity on Adverse Outcomes in Older Hospitalized Patients: A One-Year Follow-Up Study.

BACKGROUND: Intrinsic capacity (IC) is a novel view focusing on healthy aging. The effect of IC on adverse outcomes in older hospitalized Chinese adults is rarely studied. OBJECTIVES: This study focused on investigating the impact of IC domains on the adverse health outcomes including new activities of daily living (ADL) dependency, new instrumental activities of daily living (IADL) dependency, and mortality over a 1-year follow-up. METHODS: In a retrospective observational population-based study, a total of 329 older hospitalized patients from Zhejiang Hospital in China were enrolled and completed 1-year follow-up. The 5 domains of IC including cognition, locomotion, sensory, vitality, and psychological capacity were assessed at admission. The IC composite score was calculated based on these domains, and the higher IC composite score indicated the greater amount of functional capacities reserved. Multivariate logistic regression models were used to explore the association between IC at baseline and 1-year adverse outcomes. RESULTS: During the 1-year follow-up, 69 patients (22.5%) experienced new ADL dependency, 103 patients (33.6%) suffered from new IADL dependency, and 22 patients (6.7%) died. After adjusting for age, sex, education level, comorbidities, and polypharmacy, low Mini-Mental State Examination (MMSE) scores at admission predicted 1-year new ADL dependency (odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.12-4.78) and new IADL dependency (OR = 2.15, 95% CI: 1.14-4.04) among older hospitalized patients, but no significance was obtained between IC domains and mortality. Higher IC composite score at admission was associated with decreased risks of 1-year new ADL dependency (OR = 0.53, 95% CI: 0.40-0.70) and new IADL dependency (OR = 0.76, 95% CI: 0.61-0.95), and 1-year mortality (OR = 0.48, 95% CI: 0.31-0.74) after adjustment for the possible confounders. CONCLUSIONS: Loss of ICs at admission predicted adverse health outcomes including new ADL and IADL dependency and mortality 1 year after discharge among older hospitalized patients.

TNFα selectively activates the IRE1α/XBP1 endoplasmic reticulum stress pathway in human airway smooth muscle cells.

Airway inflammation is a key aspect of diseases such as asthma. Proinflammatory cytokines such as TNFα mediate the inflammatory response. In various diseases, inflammation leads to endoplasmic reticulum (ER) stress, the accumulation of unfolded proteins, which triggers homeostatic responses to restore normal cellular function. We hypothesized that TNFα triggers ER stress through an increase in reactive oxygen species generation in human airway smooth muscle (hASM) with a downstream effect on mitofusin 2 (Mfn2). In hASM cells isolated from lung specimens incidental to patient surgery, dose- and time-dependent effects of TNFα exposure were assessed. Exposure of hASM to tunicamycin was used as a positive control. Tempol (500 µM) was used as superoxide scavenger. Activation of three ER stress pathways were evaluated by Western blotting: 1) autophosphorylation of inositol-requiring enzyme1 (IRE1α) leading to splicing of X-box binding protein 1 (XBP1); 2) autophosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) leading to phosphorylation of eukaryotic initiation factor 2α; and 3) translocation and cleavage of activating transcription factor 6 (ATF6). We found that exposure of hASM cells to tunicamycin activated all three ER stress pathways. In contrast, TNFα selectively activated the IRE1α/XBP1 pathway in a dose- and time-dependent fashion. Our results indicate that TNFα does not activate the PERK and ATF6 pathways. Exposure of hASM cells to TNFα also decreased Mfn2 protein expression. Concurrent exposure to TNFα and tempol reversed the effect of TNFα on IRE1α phosphorylation and Mfn2 protein expression. Selective activation of the IRE1α/XBP1 pathway in hASM cells after exposure to TNFα may reflect a unique homeostatic role of this pathway in the inflammatory response of hASM cells.

New-onset glucose disorders in peritoneal dialysis patients: a meta-analysis and systematic review.

BACKGROUND: Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. METHODS: We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. RESULTS: We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) was 8% [95% confidence interval (CI) 4-12; I2 = 98%] adjusted by sample sizes in PD patients. Pooled incidence rates of new-onset IGT and IFG were 15% (95% CI 3-31; I2 = 97%) and 32% (95% CI 27-37), respectively. There was no significant difference in NODM risk between PD and HD [risk ratio 0.99 (95% CI 0.69-1.40); P = 0.94; I2 = 92%]. PD patients with NODM were associated with an increased risk of mortality [hazard ratio 1.06 (95% CI 1.01-1.44); P < 0.001; I2 = 92.5%] compared with non-DM PD patients. CONCLUSIONS: Around half of PD patients may develop a glucose disorder, which can affect the prognosis by significantly increasing mortality. The incidence did not differ among different ethnicities or between PD and HD. The risk factor analysis did not draw a definitive conclusion. The glucose tolerance test should be routinely performed in PD patients.

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 and Outcomes of Community-Acquired versus Hospital-Acquired Acute Kidney Injury: A Meta-Analysis.

BACKGROUND: The different clinical characteristics of community-acquired acute kidney injury (CA-AKI) versus hospital-acquired AKI (HA-AKI) have remained inconclusive, and thus, a meta-analysis was conducted to summarize and quantify the clinical significance distinguishing the 2 types of AKI. METHODS: We identified observational studies reporting the clinical characteristics and prognosis of HA-AKI and CA-AKI. ORs and mean differences (MDs) were extracted for each outcome and the results aggregated. The primary outcome was defined as the mortality rate; renal recovery, oliguria incidence, dialysis, intensive care unit (ICU) requirement, and length of hospital stay were secondary outcomes. RESULTS: Fifteen eligible studies involving 46,157 patients (22,791 CA-AKI patients and 23,366 HA-AKI patients) were included. Mortality was significantly lower in CA-AKI than in HA-AKI patients, with an OR of 0.43 (95% CI 0.35-0.53). The incidence of oliguria and need for ICU were also lower in CA-AKI patients (OR 0.58, 95% CI 0.38-0.88; OR 0.24, 95% CI 0.14-0.40, respectively). CA-AKI patients had a shorter hospital stay (MD -9.42, 95% CI -13.73 to -5.12). The renal recovery rate and dialysis need between CA- and HA-AKI were similar (OR 1.27, 95% CI 0.53-3.02; OR 1.05, 95% CI 0.82-1.34, respectively). CONCLUSIONS: CA-AKI showed better clinical manifestations with a lower incidence of oliguria, reduced risk of ICU treatment, and shorter hospital stay. Mortality associated with CA-AKI was lower compared with HA-AKI, indicating a better prognosis. The rate of renal recovery and need for dialysis showed no significant difference between the 2 groups.

LC-MS/MS method for simultaneous determination of serum p-cresyl sulfate and indoxyl sulfate in patients undergoing peritoneal dialysis.

p-Cresol sulfate (pCS) and indoxyl sulfate (IS) are protein-bound uremic toxins that accumulate in patients with chronic kidney disease (CKD). They are closely associated with the mortality rate of CKD and morbidity of cardiovascular disease. In the present study, we established a rapid method for determination of pCS and IS by HPLC-MS/MS in serum samples from 205 CKD patients undergoing peritoneal dialysis. In brief, serum was extracted by acetonitrile and spiked with hydrochlorothiazide. The prepared sample was eluted through HPLC column (Agilent Zorbax SB-C18 , 3.5 µm, 2.1 × 100 mm) with a mobile phase of acetonitrile and 10 mm ammonium acetate solution (10:90, v/v) for subsequent detection of pCS and IS by MS/MS. The linearity ranged from 50 to 10,000 ng/mL for pCS (r > 0.99), and from 500 to 10,000 ng/mL for IS (r > 0.99). The lower limit of quantification was 50 ng/mL for pCS, and 500 ng/mL for IS. Relative standard deviation (RSD) of intra- and inter-day precision was within ±15%. The results showed that pCS and IS levels were partially correlated with renal function in CKD patients, and IS was directly related to serum creatinine and estimated glomerular filtration rate.

Calcific uremic arteriolopathy ameliorated by hyperbaric oxygen therapy in high-altitude area.

BACKGROUND: Calcific uremic arteriolopathy (CUA), previously called calciphylaxis, is a devastating complication of end-stage kidney disease (ESKD) with an annual incidence of 1-4% in dialysis patients and the mortality is as high as 80%. The rarity of the disease and the multifactorial nature of its causes have compromised good evidences that could determine the best therapy for the condition. For inhabitants in high-altitude area, the content of oxygen in the air is significantly lower than that in sea level area, which leads to the differences in the clinical manifestations and treatments to CUA. CASE PRESENTATION: We presented a patient with CUA on Tibetan Plateau successfully treated by hyperbaric oxygen (HBO). This 46-year-old uremic Tibetan peasant received hemodialysis for 10 years, and over the last six months, skin necrosis occurred progressively on the distal joint of the middle finger of his right hand and the distal knuckles became paled, hardened, and severely painful. Extensive calcification of the arteries of both hands was revealed and his serum phosphorus elevated and serum calcium decreased. After diagnosis of CUA, patient was treated with HBO therapy for successive three weeks with a session per day, on the basis of secondary infection prevention. Pain of the affected finger was quickly alleviated in one week and the lesions of the affected finger healed in two months. CONCLUSION: As the dialysis population in high-altitude area increasing rapidly in recent years, this management strategy of improving focal oxygen supply by HBO might act as a reference for the treatment of CUA patients in similar conditions.

PGC1α enhances macrophage efferocytosis in ox-LDL-stimulated RAW264.7 cells by regulating the NLRP3/PPARα axis.

BACKGROUND: Defective clearance of apoptotic and foam cells achieved by arterial macrophage efferocytosis propels the progression of inflammatory atherosclerosis, but related molecular mechanisms in this process remain unclear. Herein, this study is engineered to probe into the mechanism of peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC1α) on atherosclerosis. METHODS: The PGC1α/NLR family pyrin domain containing 3 (NLRP3)/peroxisome proliferator activated receptor alpha (PPARα) axis in oxidized low-density lipoprotein (ox-LDL)-induced RAW264.7 cells was verified using Western blot. Inflammatory response, NLRP3 activation, efferocytotic efficiency and lipid uptake of the ox-LDL-stimulated cells overexpressing PGC1α or/and silencing PPARα were detected by enzyme-linked immunosorbent assay, immunofluorescence, tracing of apoptotic Jurkat cells and Oil red O staining. RESULTS: PGC1α and PPARα levels were decreased, but NLRP3 level was increased in ox-LDL-stimulated RAW264.7 cells (P<0.001). PGC1α overexpression repressed the levels of IL-1ß, IL-6 and TNF-α, NLRP3 expression or activation and foam cell formation (P<0.05), but enhanced efferocytosis as well as expressions of AXL, MERTK and TYRO3 in ox-LDL-stimulated cells (P<0.001). PGC1α overexpression increased PPARα expression. However, PPARα silencing reversed the effects of PGC1α overexpression on protecting macrophages against ox-LDL-induced inflammation, efferocytotic impairment and foam cell formation (P<0.05). CONCLUSION: Overexpression PGC1α decreased NLRP3 activation to promoted the expression of PPARα, which alleviated the impairment of macrophage efferocytosis and inhibited the development of atherosclerosis development.

Genotype and Phenotype of Renal Hypouricemia: A Single-Center Study from China.

BACKGROUND: Renal hypouricemia (RHUC), a rare inherited disorder characterized by impaired uric acid reabsorption and subsequent profound hypouricemia, occurs mainly due to variants in SLC22A12 or SLC2A9. Only anecdotal cases and one small-scale RHUC screening study have been reported in the Chinese population. METHODS: A total of 19 patients with RHUC from 17 unrelated families were recruited from our center. The medical history, clinical manifestations, biochemical exam, and clinical outcomes were collected. Next-generation sequencing-based targeted gene sequencing or whole exon sequencing was performed. RESULTS: A total of 22 variants in SLC22A12 or SLC2A9 were found in 19 patients. The variant c.944G>A (p.W315X) in SLC2A9 was identified in three patients. Three variants c.165C>A (p.D55E), c.1549_1555delGAGACCC (p.E517Rfs*17), and c.1483T>C (p.W495R) in SLC22A12 and three variants c.1215+1G>A (splicing variant), c.643A>C (p.T215P), and c.227C>A (p.S76X) in SLC2A9 were novel. A proportion of 10 out of 19 patients presented with exercise-induced acute kidney injury (EIAKI). The renal outcome was favorable. Five patients had nephrolithiasis, in whom three had hypercalciuria. CONCLUSION: The current study reported six novel variants in SLC22A12 and SLC2A9 genes of Chinese patients with RHUC. The variant c.944G>A (p.W315X) in SLC2A9 may be common in Chinese patients. EIAKI is the main clinical phenotype associated with RHUC in our cohort, with a favorable outcome. Hypercalciuria presented in some RHUC patients is a new finding.

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.

Factors Affecting Mortality in Elderly Hypertensive Hospitalized Patients with COVID-19: A Retrospective Study.

Purpose: Corona Virus Disease 2019 (COVID-19) endangers the health and survival of the elderly. We tried to explore factors especially kidney function which affected mortality in elderly hypertensive patients with COVID-19. Methods: We conducted a retrospective research of 748 COVID-19 elderly patients (≥65 years old) at Zhejiang Hospital. This study compared demographic data, laboratory values, comorbidities, treatments, and clinical outcomes of hypertension and non-hypertension participants, and subgroup analysis of age and frailty was conducted in the hypertension population. Survival analysis was used to determine risk factors for death in elderly patients with COVID-19. Results: Our study revealed that the elderly hypertensive patients with COVID-19 had higher blood urea nitrogen (BUN), serum uric acid (UA), serum creatinine (Scr), lower estimated glomerular filtration rate (eGFR), higher incidence of severity, admission to intensive care unit (ICU) and death, and longer in-hospital stay than non-hypertensive patients, which also occurred in the very elderly hypertensive patients compared with younger hypertensive patients and frail hypertensive patients compared with no-frail hypertensive patients. In addition, the prevalence of acute kidney injury (AKI) was higher in the oldest old hypertensive patients and frail hypertensive patients. Multivariate survival analysis indicated that the independent risk factors for death from COVID-19 were age ≥80 years, heart failure, antiviral therapy, calcium channel blocker (CCB) therapy, mechanical ventilation, AKI, and eGFR<60 mL/min per 1.73 m2. Conclusion: The results of the present study suggested that the elderly hypertensive patients with COVID-19 would have more serious kidney injury, more serious disease progression and higher mortality, which also occurred in very elderly and frailty subgroup. Kidney dysfunction was closely related to mortality in elderly patients with COVID-19.

Cullin-3 intervenes in muscle atrophy in the elderly by mediating the degradation of nAchRs ubiquitination.

Sarcopenia involves in the loss of muscle mass associated with aging, which is the major cause of progressive muscle weakness and deterioration in older adults. Muscle atrophy is a direct presentation of sarcopenia, and it greatly contributes to the decline in quality of life among older adults. Neuromuscular junction (NMJ) stability is the key link to maintain muscle function. Besides, the degenerative change of NMJ promotes the process of muscle atrophy in the elderly. Based on previous transcriptome sequencing and bioinformatics analyses of aged muscle, this study used the 18-month-old aged mouse model and the 6-month-old young mouse model to deliberate the role and underlying mechanisms of Cullin-3 (Cul3) in age-related muscle atrophy. The results of reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblotting analysis showed that the expression of CUL3 increased in aged muscle tissue, while the expression level of postsynaptic membrane nicotinic acetylcholine receptors (nAChRs) decreased significantly, which manfested a negative correlation. Meanwhile, immunofluorescence demonstrated that Cul3 was highly expressed in senile muscle NMJ. The results of ubiquitin indicated that the ubiquitin level of aged muscle nAChRs was evidently increased. Co-immunoprecipitation furtherly verified the correlation between Cul3 and nAChRs. Taken together, Cul3 may mediate the ubiquitination degradation of nAChRs protein at the NMJ site in aged mice, leading to NMJ degeneration and accelerated atrophy of fast-twitch muscle fibers in aged muscle. As a prominent element to maintain the stability of NMJ, Cul3 is supposed to be one of candidate intervention targets in sarcopenia.

Associations of intrinsic capacity, fall risk and frailty in old inpatients.

Introduction: This study explored the associations of intrinsic capacity (IC), fall risk, and frailty in geriatric inpatients. Methods: A total of 703 hospitalized patients aged 75 years or older were recruited for this retrospective observational study from Zhejiang Hospital using a comprehensive geriatric assessment. The IC composite score was constructed from the scores of the Chinese version of the Mini-Mental State Examination, Short Physical Performance Battery, Short Form Mini Nutritional Assessment, 15-item Geriatric Depression Scale, and self-reported hearing and vision impairment. Adverse outcomes were recorded as the fall risk and frailty using the Morse Fall Scale and the Clinical Frailty Scale. Spearman's correlation coefficient analyses and multivariate logistic regression models were used to explore the associations between IC, high fall risk, and frailty. Results: Declined IC composite scores were associated with increased risks of falls [odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.57-0.72] and frailty (OR = 0.45, 95%CI: 0.37-0.54) among older hospitalized patients after adjusting for the related potential confounders. In addition, decreased cognitive, vitality, locomotion, and psychological scores were associated with increased adverse health conditions, with ORs ranging from 0.26 to 0.70. Vision impairment was observed to increase the risk of frailty (OR = 0.42, 95%CI: 0.23-0.76) after adjusting for the related potential confounders. Discussion: This study indicated that declined IC was associated with fall risk and frailty in older inpatients. Further prospective studies are needed to explore the longitudinal associations between baseline IC and subsequent risk of falls and frailty.