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Background: Leukocyte telomere length shortening is a characteristic of premature senescence, a process that can be accelerated by oxidative stress. In general, patients with end-stage renal disease undergoing regular hemodialysis (HD) are repeatedly exposed to oxidative stress. Patients undergoing HD tend to have cardiovascular diseases associated with oxidative stress and inflammation. Therefore, we assumed that telomere length is associated with HD vintage and the degree of vascular calcification. Methods: A total of 144 patients undergoing regular HD before kidney transplantation and 62 patients on hemodialysis, but not undergoing kidney transplantation, were enrolled. We measured common laboratory values, such as calcium, phosphate, and hemoglobin levels, and assessed the degree of vascular calcification in the patients. The leukocyte telomere length was measured using reverse transcription polymerase chain reaction, and Spearman correlation was used for correlation analysis. Results: The leukocyte telomere length was negatively associated with age (rho = −0.306, P＜0.01); it was shorter in middle-aged patients than in young patients (13.48 ± 4.80 vs. 15.86 ± 4.51, P

Purpose To examine the “age-related positivity effect” and its sex differences in the pain-depression relationship among Chinese community-dwelling older adults. Design Cross-sectional design. Methods The study was conducted with a sample of 1,913 older adults in Jinan, China. Data were collected on pain intensity, age, sex, depressive symptoms, and potential covariates. Results The hierarchical linear regression analyses revealed that pain intensity was significantly related to depressive symptoms, there was a significant two-way interaction between age and pain intensity, and there was a significant three-way interaction between sex, age, and pain intensity. The Johnson-Neyman plot revealed that the relationship between pain and depressive symptoms decreased with advancing age, indicating an “age-related positivity effect.” And the age-related positivity effect in the pain-depression relationship was significant only in men, but not in women. Conclusions The study suggests that all older women and “young-old” men (younger senior citizens aged 60-79) in China are more likely to experience depressive symptoms from pain. Interventions on cognitive psychology should particularly target all older women and young-old men to reduce the detrimental effect of pain on emotional well-being.

We aimed to explore the relationship between sleep quality and frailty, and depression as a mediator and its interaction with sleep quality on frailty. This was a cross-sectional study among 936 Chinese community-dwelling adults aged≥60 years. Sleep quality, frailty and depression were measured by the Pittsburgh Sleep Quality Index (PSQI), the Frailty Phenotype and the 5-item Geriatric Depression Scale (GDS-5), respectively. We found that depression mediated the association between poor sleep quality and physical frailty, attenuating the association between poor sleep and physical frailty by 51.9%. Older adults with both poor sleep quality and depression had higher risk of frailty than those with poor sleep quality or depression alone. These results implicate multidisciplinary care for frail older adults with poor sleep quality.

Podocyte injury plays a vital role in proteinuria and nephrotic syndrome. Calcineurin (CaN) inhibitors are effective in reducing proteinuria. However, their molecular mechanism is still not fully understood. Angiopoietin-like-4 (ANGPTL4) is a secreted protein that mediates proteinuria in podocyte-related nephropathy. In this study, we established a puromycin aminonucleoside (PAN)-induced minimal-change disease (MCD) rat model and a cultured podocyte injury model. We found that CaN inhibitors protected against PAN-induced podocyte injury, accompanied by an inhibition of Nfatc1 and Angptl4 both in vivo and in vitro. Nfatc1 overexpression and knockdown experiments indicated that Angptl4 was regulated by Nfatc1 in podocytes. ChIP assays further demonstrated that Nfatc1 increased Angptl4 expression by binding to the Angptl4 promoter. In addition, overexpression and knockdown of Angptl4 revealed that Angptl4 directly induced rearrangement of the cytoskeleton of podocytes, reduced the expression of synaptopodin, and enhanced PAN-induced podocyte apoptosis. Furthermore, in a cohort of 83 MCD and 94 membranous nephropathy (MN) patients, we found increased expression of serum ANGPTL4 compared to 120 healthy controls, and there were close correlations between serum ANGPTL4 and Alb, urinary protein, urinary Alb, eGFR, Scr, and BUN in MCD patients. No obvious correlation was found in MN patients. Immunofluorescence studies indicated that increased ANGPTL4 in MCD and MN patients was located mostly in podocytes. In conclusion, our results demonstrate that CaN inhibitors ameliorate PAN-induced podocyte injury by targeting Angptl4 through the NFAT pathway, and Angptl4 plays a vital role in podocyte injury and is involved in human podocyte-related nephropathy. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

This study aims to examine age differences in the relationship between frailty and depression among older adults METHODS: A total of 1789 community-dwelling older adults were recruited from eastern China. Physical frailty and depressive symptoms were assessed using the Frailty Phenotype and the 5-item Geriatric Depression Scale, respectively.The hierarchical multiple linear regression analysis revealed that frailty was significantly related to depressive symptoms (β = 0.272, P0.001) and there was a significant interaction between age and frailty (β = -0.703, P0.001). The Johnson-Neyman plot revealed that the relationship between frailty and depressive symptoms became weaker as people aged.Frailty is more likely to cause depressive symptoms among the young-old than among the old-old, reflecting the age-related positivity effect. This highlights that interventions on emotional regulation should particularly target the young-old to reduce the effect of frailty on depression.

Background and aims: Currently, there are no definitive therapies for coronavirus disease 2019 (COVID-19). Gut microbial dysbiosis has been proved to be associated with COVID-19 severity and probiotics is an adjunctive therapy for COIVD-19. However, the potential benefit of probiotics in COVID-19 has not been studied. We aimed to assess the relationship of probiotics use with clinical outcomes in patients with COVID-19. Methods: We conducted a propensity-score matched retrospective cohort study of adult patients with COVID-19. Eligible patients received either probiotics plus standard care (probiotics group) or standard care alone (non-probiotics group). The primary outcome was the clinical improvement rate, which was compared among propensity-score matched groups and in the unmatched cohort. Secondary outcomes included the duration of viral shedding, fever, and hospital stay. Results: Among the propensity-score matched groups, probiotics use was related to clinical improvement rates (log-rank p = 0.028). This relationship was driven primarily by a shorter (days) time to clinical improvement [difference, −3 (−4 to −1), p = 0.022], reduction in duration of fever [−1.0 (−2.0 to 0.0), p = 0.025], viral shedding [−3 (−6 to −1), p Conclusion: Our study suggested that probiotics use was related to improved clinical outcomes in patients with COVID-19. Further studies are required to validate the effect of probiotics in combating the COVID-19 pandemic.

Sepsis is a heterogeneous syndrome induced by infection and results in high mortality. Even though more than 100 biomarkers for sepsis prognosis were evaluated, prediction of patient outcomes in sepsis continues to be driven by clinical signs because of unsatisfactory specificity and sensitivity of these biomarkers. This study aimed to elucidate the key candidate genes involved in sepsis response and explore their downstream effects based on weighted gene co-expression network analysis (WGCNA). The dataset GSE63042 with sepsis outcome information was obtained from the Gene Expression Omnibus (GEO) database and then consensus WGCNA was conducted. We identified the hub gene SDF4 (stromal cell derived factor 4) from the M6 module, which was significantly associated with mortality. Subsequently, two datasets (GSE54514 and E-MTAB-4421) and cohort validation (n=89) were performed. Logistic regression analysis was used to build a prediction model and the combined score resulting in a satisfactory prognosis value (area under the ROC curve=0.908). The model was subsequently tested by another sepsis cohort (n=70, ROC= 0.925). We next demonstrated that endoplasmic reticulum (ER) stress tended to be more severe in patients PBMCs with negative outcomes compared to those with positive outcomes and SDF4 was related to this phenomenon. In addition, our results indicated that adenovirus-mediated Sdf4 overexpression attenuated ER stress in cecal ligation and puncture (CLP) mice lung. In summary, our study indicates that incorporation of SDF4 can improve clinical parameters predictive value for the prognosis of sepsis, and decreased expression levels of SDF4 contributes to excessive ER stress, which is associated with worsened outcomes, whereas overexpression of SDF4 attenuated such activation.

MYH9-related disease or disorder (MYH9-RD) is an autosomal dominant disease caused by mutations in the MYH9 gene. Mutations in this gene initially affect the hemic system, and other manifestations may evolve with age. Here, we report the case of a 46-year-old Chinese woman with MYH9-RD who was primarily misdiagnosed with idiopathic thrombocytopenia purpura. Exome sequencing of the patient, and the mother and son of the patient revealed a deletion mutation c.5797delC (p. R1933Efs*15) in exon 41 (encoding non-helical tailpiece, NHT) of the MYH9 gene, which consequently led to a frameshift mutation. To the best of our knowledge, this mutation has been reported in Italy once, while the substitution mutation c.5797 C>T is the most frequent mutation. Mutations that affect the NHT region cause thrombocytopenia throughout life; however, our patient presented with a more severe phenotype than previously reported, including thrombocytopenia, inclusion bodies in neutrophils, sensorineural hearing loss, nephropathy, and abnormal liver enzymes. Our goal in the current case is to prevent further progression of renal involvement and to identify other affected members in this family to provide early intervention. This case may raise awareness of MYH9-RD when diagnosing thrombocytopenia and improve our understanding of this condition.

To examine the diagnostic test accuracy (DTA) of the FRAIL-NH and four frailty screening instruments among institutionalized older adults.Cross-sectional study.Institutionalized setting, Jinan, China.A total of 305 older adults (mean age 79.3 ± 8.4 years, 57.0% female) were enrolled from nursing homes.Frailty was assessed by the FRAIL-NH, Physical Frailty Phenotype (PFP), FRAIL, Tilburg Frailty Indicator (TFI), and Groningen Frailty Indicator (GFI), respectively. The Comprehensive Geriatric Assessment (CGA) was used as a reference standard of frailty. The receiver operating characteristic (ROC) curve was plotted to examine the DTA of five frailty screening instruments against the CGA. The optimal cut-point was determined by the maximum value of the Youden index (YI, calculated as sensitivity + specificity - 1).The prevalence of frailty ranged from 25.9% (FRAIL) to 56.4% (GFI). Areas under the curve (AUCs) against the CGA ranged from 0.80 [95% confidence interval (CI) 0.74 - 0.85: FRAIL] to 0.83 (95% CI 0.78 - 0.88: PFP). At their original cut-points, all five frailty screening instruments presented low sensitivity (32.9% - 69.3%) and high specificity (80.0% - 93.8%), as well as high positive predictive values (90.7% - 94.9%) and low negative predictive values (33.2% - 48.1%). At their optimal cut-points, the sensitivity and specificity of the FRAIL-NH, PFP, and FRAIL tended to be balanced, and their correctly classified rates (76.1% - 81.3%) and kappa values (0.465 - 0.523) increased a lot. ROC contrasts showed that all five frailty screening instruments had similarly good diagnostic accuracy (χ2: 0.0003 - 1.38, P.05).In the institutionalized setting, the specific FRAIL-NH, self-report FRAIL, TFI, and GFI as well as hybrid PFP, show similarly good diagnostic properties in identifying frailty against the CGA.

Background Chronic pain (CP) is prevalent among older adults in many Western countries and its prevalence, factors, and self-reported or objective measured health impacts have been well documented. However, there is limited information on these aspects among Chinese community-dwelling older adults. Aims Our aim was to assess the prevalence of CP and identify its associated factors as well as health impacts among older adults in China. Design Cross-sectional design. Settings Community settings. Participants/Subjects A total of 1219 community-dwelling adults aged 60 years or older. Methods Data on CP, sociodemographic characteristics, comorbidity, cognitive function, and physical activity, as well as self-reported outcomes (functional disability, depression, quality of sleep, and undernutrition) and objective measured physical function, were obtained. Results Among 1,219 participants, 41.1% reported CP, of whom 16.6% experienced moderate to severe pain. The risk of CP was higher among older women with comorbidity and with depression and lower among older adults with higher educational level as well as with adequate physical activity. CP had significant associations with inadequate physical activity, functional disability, depression, poorer quality of sleep, and undernutrition, as well as worsening physical performance, poorer standing balance, and chair stands. Conclusions CP is a common problem among Chinese community-dwelling older adults, particularly among the most vulnerable subgroups, and has substantial impacts on self-reported functional disability, depression, poor quality of sleep, and undernutrition, as well as objective measured physical function. Therefore it is relevant for older adults to develop effective CP management programs.

BACKGROUND Hyperphosphatemia, hypocalcemia, and elevation of parathyroid hormone (PTH) are typical abnormalities of uremic patients with Secondary hyperparathyroidism (SHPT). However, metabolic imbalance associated with SHPT is not well understood. METHODS A total of 15 SHPT patients with an intact parathyroid hormone (iPTH) level > 600 pg/mL were set as preoperative (PR) group, 15 age- and gender-matched controls who had undergone parathyroidectomy plus forearm transplantation because of hyperparathyroidism and achieved an iPTH level

Objective To examine the predictive value of intrinsic capacity on one-year incident adverse outcomes among community-dwelling older adults. Methods A total of 756 community-dwelling older adults aged ≥ 60 years were followed up after 1 year. Intrinsic capacity was assessed using the revised integrated care for older people screening tool. Adverse outcomes included incident disability, recurrent falls, hospitalization, emergency department visits, and poor quality of life. Multivariate logistic regression models were performed to evaluate the predictive value of intrinsic capacity domains on adverse outcomes. Results Cognitive decline, limited mobility, visual impairment and depressive symptoms predicted incident disability. Visual impairment predicted recurrent falls. Cognitive decline and limited mobility predicted emergency department visits. Limited mobility predicted poor quality of life. Discussion Intrinsic capacity could predict incident adverse outcomes among community-dwelling older adults. Assessing intrinsic capacity would facilitate early identification of older adults at high risk of adverse outcomes and prompt targeted interventions.

BackgroundIncreasing evidence shows that Angptl4 affects proteinuria in podocytes injured kidney disease, however, whether there is a relationship between Angptl4 and IgA nephropathy (IgAN) has not been studied yet.MethodsPlasma and urine samples were obtained from 71 patients with IgAN and 61 healthy controls. Glomeruli from six renal biopsy specimens (three IgAN patients and three healthy controls) were separated by RNA-Seq. Differentially expressed genes (DEGs) related to podocytes and Angptl4 between IgAN patients and healthy controls were performed using the Limma package. Gene set enrichment analysis was used to determine whether there was a statistically significant difference between the two groups. STRING was used to create a protein-protein interaction network of DEGs. Association analysis between Angptl4 levels and clinical features of IgAN was performed.ResultsThirty-three podocyte-related and twenty-three Angpt4-related DEGs were found between IgAN patients and healthy controls. By overlapping the genes, FOS and G6PC were found to be upregulated in IgAN patients, while MMP9 was downregulated in IgAN patients. Plasma and urine Angptl4 levels were closely related to the degree of podocyte injury and urine protein, but not to the protein-creatine ratio.ConclusionOur findings show that Angptl4 levels in plasma and urine are related to podocyte damage and, therefore, may be a promising tool for assessing the severity of IgAN patients to identify and reverse the progression to ESRD.

Objective To examine the moderating effects of age and sex in the role of functional disability as a mediator between pain and depression. Methods Participants were 1917 community-dwelling older adults from Jinan, China. Data were collected on pain intensity, functional disability in activities of daily living and instrumental activities of daily living, depressive symptoms and covariates. Results Functional disability partially mediated the relationship between pain intensity and depressive symptoms (estimate = 0.015, SE = 0.007, 95% CI [0.004, 0.030]). Age and sex moderated both the direct and indirect effect of the mediation model. The mediating effect of functional disability was significant in the old-old men, young-old men, and young-old women, but not in the old-old women. Conclusions Interventions should target both pain and pain-related functional disability to improve their emotional well-being among community-dwelling older adults. Importantly, strategies should be tailored across different age and sex groups to improve their effectiveness.

Disturbed intrauterine development increases the risk of renal disease. Various studies have reported that Notch signalling plays a significant role in kidney development and kidney diseases. A disintegrin and metalloproteinase domain 10 (ADAM10), an upstream protease of the Notch pathway, is also reportedly involved in renal fibrosis. However, how ADAM10 interacts with the Notch pathway and causes renal fibrosis is not fully understood. In this study, using a prenatal chlorpyrifos (CPF) exposure mouse model, we investigated the role of the ADAM10/Notch axis in kidney development and fibrosis. We found that prenatal CPF‐exposure mice presented overexpression of Adam10, Notch1 and Notch2, and led to premature depletion of Six2+ nephron progenitors and ectopic formation of proximal tubules (PTs) in the embryonic kidney. These abnormal phenotypic changes persisted in mature kidneys due to the continuous activation of ADAM10/Notch and showed aggravated renal fibrosis in adults. Finally, both ADAM10 and NOTCH2 expression were positively correlated with the degree of renal interstitial fibrosis in IgA nephropathy patients, and increased ADAM10 expression was negatively correlated with decreased kidney function evaluated by serum creatinine, cystatin C, and estimated glomerular filtration rate. Regression analysis also indicated that ADAM10 expression was an independent risk factor for fibrosis in IgAN. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

We aimed to compare the diagnostic test accuracy (DTA) of six frailty screening tools against comprehensive geriatric assessment (CGA) in the community. A total of 1177 community-dwelling older people were recruited. Frailty was assessed by purely physical tools including Physical Frailty Phenotype (PFP), FRAIL (fatigue, resistance, ambulation, illness and loss of weight), Study of Osteoporotic Fracture (SOF), and multidimensional tools including Tilburg Frailty Indicator (TFI), Groningen Frailty Indicator (GFI) and Comprehensive Frailty Assessment Instrument (CFAI). The receiver operating characteristic curve analyses were performed. The GFI, TFI and CFAI [areas under the curve (AUCs): 0.78-0.80] had better diagnostic accuracy than SOF, PFP and FRAIL (AUCs: 0.69-0.72) (χ2: 6.37-26.76, P

Organ dysfunction caused by sepsis is life-threatening and results in high mortality. Therapeutic options for sepsis are limited. Pathogenic factors are considered as components of environmental pressure that modify DNA methylation patterns thereby enhancing disease progression. Here, we found that sepsis patients exhibited higher levels of genomic DNA methylation patterns and hypermethylated genes associated with the NF-kB signaling pathway. Therefore, we hypothesized that a DNA methyl transferase inhibitor, Decitabine, may mitigate inflammation and improve survival by inhibiting the NF-κB signaling pathway. To test the hypothesis, mice challenged with caecal ligation and puncture (CLP) were subcutaneously injected with Decitabine solution (0.5, 1, and 1.5 mg/kg) 2 h following operation. Our results indicated that Decitabine reduces DNA methyltransferases (DNMTs), attenuates NF-κB activation, downregulates inflammatory cytokine levels, and inhibits the progression of sepsis. Thus, DNA methylation may be indispensable for sepsis and serve as a predicting factor. The use of Decitabine could represent a novel strategy in the treatment of sepsis.

Acute rejection (AR) can lead to allograft dysfunction following renal transplantation, despite immunosuppressive treatments. Accumulating evidence points out a role for epigenetic modification in immune responses. However, the mechanism and contribution of DNA methylation in allograft survival remain unclear. In this study, we followed up patients who successively experienced end‐stage renal disease, renal transplantation with allograft function or dysfunction, and hemodialysis. Peripheral blood mononuclear cells were collected at different time points for analysis of the DNA methylation. Epigenetic modifier analysis was also performed to explore its effect of methylation in a mouse model of AR. Compared with the allograft‐stable cohort, patients who experienced AR‐induced allograft dysfunction demonstrated more changes in methylation patterns. Pathway analysis revealed that the hypermethylated areas in the allograft dysfunction group were associated with genes related to the mechanistic target of rapamycin (mTOR) signaling pathway. Moreover, in the mouse AR model, treatment with the DNA methyltransferase inhibitor—decitabine regulated the Th1/2/17/regulatory T cell (Treg cell) immune response via its demethylating role in the suppressing the activity of the mTOR pathway, which ultimately ameliorated renal allograft‐related inflammatory injuries. These results revealed that changes in methylation accompany AR‐induced allograft dysfunction after renal transplantation. Epigenetics may provide new insights into predicting and improving allograft survival., Whole‐genome bisulfite sequencing explores epigenetic changes in renal transplant recipients, revealing enhanced hypermethylation of genes enriched in immune‐related pathways.

To cross-culturally adapt and test the FRAIL scale in Chinese community-dwelling older adults.Cross-sectional study.The Chinese FRAIL scale was generated by translation and back-translation. An urban sample of 1235 Chinese community-dwelling older adults was enrolled to test its psychometric properties, including convergent validity, criterion validity, known-group divergent validity, internal consistency and test-retest reliability.The Chinese FRAIL scale achieved semantic, idiomatic, and experiential equivalence. The convergent validity was confirmed by statistically significant kappa coefficients (0.209-0.401, P .001) of each item with its corresponding alternative measurement, including the 7th item of the Center for Epidemiologic Studies-Depression Scale, the Timed Up and Go test, 4-m walking speed, polypharmacy, and the Short-Form Mini Nutritional Assessment. Using the Fried frailty phenotype as an external criterion, the Chinese FRAIL scale showed satisfactory diagnostic accuracy for frailty (area under the curve = 0.91). The optimal cut-point for frailty was 2 (sensitivity: 86.96%, specificity: 85.64%). The Chinese FRAIL scale had fair agreement with the Fried frailty phenotype (kappa = 0.274, P .001), and classified more participants into frailty (17.2%) than the Fried frailty phenotype (3.9%). More frail individuals were recognized by the Chinese FRAIL scale among older and female participants than their counterparts (P .001), respectively. It had low internal consistency (Kuder-Richardson formula 20 = 0.485) and good test-retest reliability within a 7- to 15-day interval (intraclass correlation coefficient = 0.708).The Chinese FRAIL scale presents acceptable validity and reliability and can apply to Chinese community-dwelling older adults.

Pain and frailty are both prevalent and have severe health impacts among older adults. We conducted a cross-sectional observational study to examine the association between pain and frailty, and depression as a mediator and its interaction with pain on frailty among 1788 Chinese community-dwelling older adults. Physical frailty, pain intensity, and depressive symptoms were assessed using the Frailty Phenotype, the Faces Pain Scale-revised, and the 5-item Geriatric Depression Scale, respectively. We found that both pain (odds ratio [OR] = 1.61; 95% confidence interval [CI]: 1.32-1.97) and depressive symptoms (OR = 4.67; 95% CI: 3.36-6.50) were positively associated with physical frailty (OR = 1.61; 95% CI: 1.32-1.97), and depressive symptoms were associated with pain (OR = 1.94; 95% CI: 1.15-3.39), attenuating the association between pain and physical frailty by 56.1%. Furthermore, older adults with both pain and depressive symptoms (OR = 8.13; 95% CI: 5.27-12.53) had a higher risk of physical frailty than those with pain (OR = 1.41; 95% CI: 1.14-1.76) or depressive symptoms (OR = 3.63; 95% CI: 2.25-5.85) alone. The relative excess risk of interaction, the attributable proportion due to interaction, and the synergy index (S) were 4.08, 0.50, and 2.34, respectively. These findings suggest that the positive association of pain with frailty is persistent and partially mediated by depression, and comorbid depression and pain have an additive interaction on physical frailty. It has an implication of multidisciplinary care for frail older adults with pain.

Aim To cross-culturally adapt and validate the Comprehensive Frailty Assessment Instrument (CFAI) among Chinese community-dwelling older adults. Methods The Chinese CFAI was developed through forward-backward translations. An urban sample of 1235 community-dwelling older adults received face-to-face interviews to examine the validity (construct validity and criterion validity) and reliability (internal consistency and test-retest reliability). Results The Chinese CFAI achieved semantic and idiomatic equivalence, and showed acceptable reliability and an expected factor structure, except for the social support domain. The exploratory factor analysis extracted five factors explaining 53.8% of the total variance of frailty. The confirmatory factor analysis showed that the data fit well to the second-order factor theoretical model, with a root mean square error of approximation of 0.05, Tucker-Lewis Index of 0.93 and Comparative Fit Index of 0.95. The receiver operating characteristic analysis presented an acceptable criterion validity using the Rockwood Frailty Index as an external criterion (area under the curve 0.80), with balanced sensitivity (65.31%) and specificity (81.19%) at the optimal 39-point frailty cut-off of the CFAI. Conclusions The Chinese CFAI has good validity and reliability as a practical frailty measure in Chinese community-dwelling older adults. Geriatr Gerontol Int 2018; 18: 301-307.

To explore the association between frailty and medication adherence by modeling medication beliefs (i.e., necessity and concerns) as mediators among community-dwelling older patients.This cross-sectional study was conducted among 780 Chinese older patients. Frailty, medication adherence and medication beliefs were assessed using the Comprehensive Frailty Assessment Instrument (CFAI), the 4-item Morisky Medication Adherence Scale (MMAS-4) and the Beliefs about Medicines Questionnaire-Specific (BMQ-Specific), respectively. The PROCESS SPSS Macro version 2.16.3, model 4 was used to test the significance of the indirect effects.Frailty was associated with high medication necessity (β = 0.091, p = 0.011) and high medication concerns (β = 0.297, p0.001). Medication adherence was positively associated with medication necessity (β = 0.129, p = 0.001), and negatively associated with medication concerns (β = -0.203, p0.001). Medication necessity and medication concerns attenuated the total effect of frailty on medication adherence by -13.6% and 70.3%, respectively CONCLUSION: High medication concerns among frail older patients inhibit their medication adherence, which cannot be offset by the positive effect of their high medication necessity on medication adherence.Interventions should target medication beliefs among frail older patients, particularly medication concerns, to efficiently improve their medication adherence.

Background: Renal diabetic changes are frequent in kidney transplantation (KTx) donors. Whether these diabetic changes are reversible remains a topic of debate. This study aimed to test the hypothesized reversibility of diabetic changes after KTx. Methods: C57BL/6J mice were randomly divided into three groups: the control group, early-stage group (ESG), and advanced-stage group (ASG). Diabetes mellitus (DM) was induced in mice by intraperitoneal injection of streptozotocin (STZ) at 50 mg/kg body weight for five consecutive days. Blood glucose levels ≥16.7 mmol/L were indicative of diabetic mice. The kidneys from ESG and ASG were transplanted to control mice 12 or 32 weeks after STZ injection. Kidney tissue, blood, and 24-hour urine specimens of donor and recipient mice were collected before KTx and 28 days after KTx, respectively. We measured the body weight, blood glucose, histological changes, reactive oxygen species (ROS), apoptosis. Electron microscopy was also performed to evaluate the mitochondrial morphology. The expression of NADPH oxidases (NOXs) was assessed by qRT-PCR. Results: Kidneys from early-stage diabetic mice showed evidence of lesion reversal four weeks after KTx, including decreased urinary albumin and reversal of histological changes. Besides, mitochondrial swelling, oxidative stress, apoptosis, and overexpression of NOXs in the kidneys were also suppressed. Conversely, no changes were observed in kidneys from advanced-stage diabetic mice after KTx. Conclusions: We confirmed that early-stage but not advanced-stage diabetic nephropathy (DN) is reversible, which is related to reduced NOX expression and improvement in mitochondrial function. These results indicated that kidneys with early-stage DN could be used for KTx in clinical practice, as the disease may be reversed following KTx.

Background Frailty becomes a great challenge with population aging. The proactive identification of frailty is considered as a rational solution in the community. Previous studies found that frailty instruments had insufficient predictive accuracy for adverse outcomes, but they mainly focused on long-term outcomes and constructed frailty instruments based on available data not original forms. The predictive performance of original frailty instruments for short-term outcomes in community-dwelling older adults remains unknown. Objective To examine the predictive performance of seven frailty instruments in their original forms for 1-year incident outcomes among community-dwelling older adults. Design A prospective cohort study. Settings A total of 22 communities were selected by a stratified sampling method from one Chinese city. Participants A total of 749 older adults aged ≥ 60 years (mean age of 69.2 years, 69.8% female) were followed up after 1 year. Methods Baseline frailty was assessed by three purely physical dimensional instruments (i.e. Frailty Phenotype, the Study of Osteoporotic Fracture and FRAIL Scale) and four multidimensional instruments (i.e. Frailty Index, Groningen Frailty Indicator, Tilburg Frailty Indicator and Comprehensive Frailty Assessment Instrument), respectively. Outcomes included incident disability, falls, hospitalization and the combined outcome at 1-year follow-up. The receiver operating characteristic curves were plotted to assess the predictive performance of frailty instruments. Results The areas under the curves of seven frailty instruments in predicting incident outcomes ranged from 0.55 [95% confidence interval (CI): 0.51–0.60] to 0.67 (95% CI: 0.61–0.72), with high specificity (72.3–99.2%) and low sensitivity (4.0–49.6%). Four multidimensional instruments had much higher sensitivity (20.9–49.6% versus 4.0–11.7%) than three purely physical dimensional instruments. Overall, the Frailty Index was more accurate than some instruments in predicting incident outcomes, while several self-report instruments had comparable predictive accuracy to the Frailty Index for all (FRAIL Scale) or some (Groningen Frailty Indicator and Tilburg Frailty Indicator) of the incident outcomes. Conclusions All frailty instruments have inadequate predictive accuracy for short-term outcomes among community-dwelling older adults. The Frailty Index roughly performs better but self-report instruments are comparable to the Frailty Index for all or some of the outcomes. An accurate frailty instrument needs to be developed, and the simple self-report instruments could be used temporarily as practical and efficient tools in primary care.

Background/aims Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) worldwide, and the importance of tubular injury has been highlighted in recent years. However, the underlying mechanisms and effective therapeutic targets are still unclear. In this study, we investigated mtDNA, mitochondrial dynamics, function and metabolic pathways to determine if mitochondrial damage plays a critical role in the development of tubular injury in DKD patients. Methods A cross-sectional study was carried out among healthy controls (HCs, n = 65), diabetes patients without kidney disease (DCs, n = 48) and DKD patients (n = 60). Serum, peripheral blood mononuclear cells (PBMCs) and kidney biopsy specimens were obtained from participants. Metabolomics was employed to investigate cellular metabolism. Results DKD patients had decreased mtDNA copy numbers and increased mtDNA damage compared to DCs. Mitochondrial fragmentation was specifically presented in tubules, but not in podocytes of DKD patients. The accumulation of damaged mtDNA and fragmented mitochondria resulted in increased reactive oxygen species (ROS) generation, activation of apoptosis and loss of mitochondrial membrane potential (ΔΨm) in tubules and PBMCs. Furthermore, glycolysis and tricarboxylic acid (TCA) cycle was perturbed, and increased dihydroxyacetone phosphate (DHAP) and decreased succinyl-CoA synthetase (SCS) respectively in these two metabolic pathways were identified as potential biomarkers for tubular injury in DKD. Conclusion Our study indicates that mitochondrial damage could be the hallmark of tubular injury in DKD patients, and this would provide a novel and attractive therapeutic target to improve this disease.

Background/Aims: In view of the latest findings that matrix metalloproteinase-7 (MMP-7) acted as a vital marker and pathogenic mediator of renal fibrosis in a murine model, we hypothesized that serum MMP-7 level might serve as a noninvasive prognostic biomarker in IgA nephropathy (IgAN) patients. Methods: We conducted a retrospective follow-up study of 244 IgAN patients for a median of 81.9 months. Serum MMP-7 was detected at the time of diagnosis, and renal progression was assessed by Cox proportional hazards method. Results: Compared with healthy populations, the serum levels of MMP-7 were significantly elevated in IgAN patients. Besides, serum MMP-7 levels were well correlated with renal scarring lesions characterized by glomerular sclerosis and interstitial fibrosis. Follow-up analyses revealed that increased serum MMP-7 levels were linked with a greater risk of poor renal outcome with a hazard ratio of 1.898 per doubling MMP-7 concentration. By contrast with the first quartile, the risk of deterioration in renal function elevated such that the hazard ratio for the second quartile was 1.805, 3.383 for the third, and 5.173 for the fourth quartile of the MMP-7 level. Conclusions: This study showed that the higher serum MMP-7 levels were independently associated with renal fibrosis and poor prognosis in IgAN.

In order to meet the increasing demand of data rate, the next generation Mobile Communications (5G) are becoming more heterogeneous, irregular and complex. This will lead to more complex interference environment. So the traditional fixed geometry hexagon model is no longer applicable. In order to more accurately evaluate the performance of the 5G heterogeneous network, in this paper, we proposes to analyze a downlink two-tiers heterogeneous cellular network (HCN) based on the stochastic geometry, which considers the inter-layer and intra-layer spatial correlation between the BSs. We present our empirical study on average SINR and average throughput for edge and hotspot areas. By comparing with the traditional fixed geometry hexagon model, the stochastic geometry model is more suitable and accurate for the actual 5G heterogeneous cellular networks.

// Xue Shao 1, 2, 3 , Bingjue Li 1, 2, 3 , Luxi Cao 1, 2, 3 , Ludan Liang 1, 2, 3 , Jingjuan Yang 1, 2, 3 , Yucheng Wang 1, 2, 3 , Shi Feng 1, 2, 3 , Cuili Wang 1, 2, 3 , Chunhua Weng 1, 2, 3 , Xiujin Shen 1, 2, 3 , Hong Jiang 1, 2, 3 and Jianghua Chen 1, 2, 3 1 Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China 2 Kidney Disease Immunology Laboratory, The Third Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Hangzhou, China 3 Key Laboratory of Multiple Organ Transplantation, Ministry of Health, Key Laboratory of Nephropathy, Hangzhou, China Correspondence to: Jianghua Chen, email: chenjianghua@zju.edu.cn Hong Jiang, email: annie.jh@163.com Keywords: Immunoglobulin A (IgA) nephropathy, Oxford classification, crescent lesions, meta-analysis Received: September 26, 2016 Accepted: April 07, 2017 Published: April 28, 2017 ABSTRACT The 2009 Oxford Classification of immunoglobulin A (IgA) nephropathy (IgAN) identifies four histological features as predictors of renal prognosis: mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T). However, the clinical and prognostic significance of crescent formation still remains controversial. Therefore, we performed a meta-analysis to evaluate the association between crescents and kidney outcome in IgAN. A total of 20 studies published from January 2009 to July 2016 involving 5,285 patients were included after systematic searches of PubMed and EMBASE databases. Pooled results showed that crescent lesions were associated with kidney failure (HR, 1.93; 95% CI, 1.49-2.50; P < 0.001). IgAN patients with crescents had lower eGFR levels (SMD, -0.21; 95% CI, -0.40--0.03; P = 0.023); higher proteinuria levels (SMD, 0.87; 95% CI, 0.11-1.63; P = 0.024); a larger number of patients with M1 (RR, 1.22; 95% CI, 1.07-1.40; P = 0.003), E1 (RR, 4.83; 95% CI, 3.04-7.66; P < 0.001), S1 (RR, 1.76; 95% CI, 1.11-2.80; P = 0.016) and T1/2 (RR, 2.74; 95% CI, 2.10-3.57; P < 0.001) lesions; and received immunosuppressive therapy more frequently (RD, 0.17; 95% CI, 0.11-0.23; P < 0.001). Our results suggest that crescent formation represents an efficient prognostic factor associated with progression to kidney failure and thus could be considered into the new Oxford Classification.

Aims and objectives To examine whether and how stigma influences attitudes towards seeking treatment for urinary incontinence, and whether its effect varies by symptom severity. Background Urinary incontinence is prevalent among women, but few seek treatment. Negative attitudes towards urinary incontinence treatment inhibit from seeking care. Urinary incontinence is a stigmatised attribute. However, the relationship between stigma and attitudes towards seeking treatment for urinary incontinence has not been well understood. Design This was a cross-sectional community-based study. Methods We enrolled a sample of 305 women aged 40–65 years with stress urinary incontinence from three communities in a Chinese city between May–October in 2011. Data were collected on socio-demographic characteristics, urinary incontinence symptoms, stigma and attitudes towards seeking treatment for urinary incontinence using a self-reported questionnaire. Effects of stigma were analysed using path analysis. Results Attitudes towards seeking treatment for urinary incontinence were generally negative. For the total sample, all the stigma domains of social rejection, social isolation and internalised shame had direct negative effects on treatment-seeking attitudes. The public stigma domain of social rejection also indirectly affected treatment-seeking attitudes through increasing social isolation, as well as through increasing social isolation and then internalised shame. The final model accounted for 28% of the variance of treatment-seeking attitudes. Symptom severity influenced the strength of paths: the effect of internalised shame was higher in women with more severe urinary incontinence. Conclusions Stigma enhances the formation of negative attitudes towards seeking treatment for urinary incontinence; public stigma affects treatment-seeking attitudes through internalisation of social messages. Relevance to clinical practice Stigma reduction may help incontinent women to form positive treatment-seeking attitudes and engage them in treatment. Interventions should specifically target the self-stigma domains of social isolation and internalised shame in women with urinary incontinence to most efficiently increase their use of health care.

Objectives Urinary incontinence (UI) threatens women's physical and mental health, but few women seek healthcare for their incontinence. Evidence is substantial that stigma may be associated with health service utilization for such diseases as mental illness, but sparse for UI. We examine the relationship between disease stigma and intentions to seek care for UI. Design and setting A cross-sectional community-based study was used. A purposive sample of 305 women aged 40–65 years in a Chinese city who had stress urinary incontinence (SUI) was enrolled from May to October in 2011. Measurements Data were collected on socio-demographic characteristics, UI symptoms, disease stigma and intentions to seek care. Results Social rejection was positively linearly related to intentions to seek care for UI (β = 0.207; 95% CI = 0.152, 0.784), indicating that more social rejection predicted stronger intentions to seek care. Significant curvilinear association between internalized shame and intentions to seek care was observed (β = −0.169; 95% CI = −0.433, −0.047). Compared to women with the low and high levels of internalized shame, those with the moderate level of internalized shame reported stronger intentions to seek care. Conclusion The impact of stigma on intentions to seek care varies by aspects and levels of stigma. Social rejection enhances intentions to seek care while internalized shame influences intentions to seek care in a quadratic way. The crucial step of targeted interventions will be to disentangle subgroups of SUI women with different aspects and levels of stigma.

Aims and objectives To examine the association between disease stigma and quality of life and whether disease stigma mediates the relationship between symptom severity and quality of life among community-dwelling women with stress urinary incontinence in China. Background Urinary incontinent patients perceived great stigma, which inhibited from seeking medical help. There is evidence that stigma associated with some other diseases had a complex relationship with illness severity and quality of life. However, little empirical research has examined the role that stigma plays among urinary incontinent population. Design A cross-sectional, descriptive design was used. Methods A purposive sample of 333 women with stress urinary incontinence from a Chinese city was enrolled. Data were collected on symptom severity, disease stigma and quality of life using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form, Social Impact Scale and Incontinence Quality-of-Life Measure, respectively. The mediate effect of disease stigma was analysed using a series of hierarchical regression models. Results Disease stigma negatively correlated with quality of life among stress urinary incontinent women. Social isolation and internalised shame, but not social rejection, the domains of disease stigma, partially mediated the effect of symptom severity on quality of life, attenuating the effect by 34·3% together. Conclusions Disease stigma impairs quality of life of women with stress urinary incontinence and mediates the association between symptom severity and quality of life. Health workers may improve their quality of life by addressing perceived stigma. Relevance to clinical practice Our findings suggest that in clinical practice, stigma reduction may have the potential to not only improve quality of life, but also mitigate the impact of the severity on quality of life among urinary incontinent women. Social isolation and internalised shame should be more concerned in targeted interventions.

Background Chronic disease is the leading global health threat and impairs patients’ health-related quality of life (HRQoL). Low health literacy is linked with chronic diseases prevalence and poor HRQoL. However, the interaction of health literacy with chronic disease on HRQoL remains unknown. Therefore, we examined how health literacy might modify the association between chronic disease and their HRQoL impacts. Methods We conducted a health survey of 913 poor rural women aged 23–57 years in Northwestern China. We assessed health literacy and HRQol using the revised Chinese Adult Health Literacy Questionnaire (R-CAHLQ) and Euroqol-5D (EQ-5D), respectively. Low health literacy was indicated by a cut-off of less than the mean of the factor score. Self-reported preexisting physician-diagnosed chronic disease and socio-demographic characteristics were also included. We fitted log-binomial regression models for each dimension of EQ-5D to examine its association with health literacy and chronic disease. We also ran linear regression models for EQ VAS scores and utility scores. Results The low health literacy group was 1.33 times more likely to have a chronic disease than the high health literacy group. Pain/discomfort was the most prevalent impairment, and was more common in the low health literacy group (PR [prevalence ratio] = 1.23; 95% CI = 1.01, 1.50). Chronic disease strongly predicted impairments in all the EQ-5D dimensions, with PRs ranging from 2.14 to 4.07. The association between chronic disease and pain/discomfort varied by health literacy level (health literacy × chronic disease: P = 0.033), and was less pronounced in the low health literacy group (PR = 2.15; 95% CI = 1.76, 2.64) than in the high health literacy group (PR = 3.19; 95% CI = 2.52, 4.05). The low health literacy group had lower VAS scores and utility scores, and slightly less decrement of VAS scores and utility scores associated with chronic disease. Conclusions Health literacy modified the impacts of chronic disease on HRQoL, and low health literacy group reported less HRQoL impacts related to chronic disease. Research should address health literacy issues as well as root causes of health disparities for vulnerable populations.