Identification and validation of a CCL18-related signature for prediction of overall survival in patients with uveal melanoma.

Uveal melanoma (UM), the most frequent primary intraocular tumor in adults, has poor prognosis. High C-C motif chemokine ligand 18 (CCL18) has been detected in various tumors and is closely correlated with patients' clinicopathological characteristics. However, the essential role of CCL18 in UM remains unclear. Therefore, this study aimed to explore the prognostic value of CCL18 in UM. Uveal melanoma cells (M17) were transfected with pcDNA3.1-CCL18 si-RNA using Lipofectamine™ 2000. Cell growth and invasion abilities were measured through Cell Counting Kit-8 assay and invasion assay. RNA expression data and clinical and histopathological details were downloaded from the UM in The Cancer Genome Atlas (TCGA-UM) and GSE22138 datasets, which were defined as the training and validation cohorts, respectively. Univariate and multivariate Cox regression analyses were performed to identify significant prognostic biomarkers. The coefficients of these significant biomarkers generated by multivariate Cox proportional hazard regression analysis were used to establish a risk score formula. Functional enrichment analyses were also carried out. We found that downregulated CCL18 inhibits M17 cell growth and invasion in vitro. CCL18 may affect UM progression by altering C-C motif receptor 8 related pathways. Higher CCL18 expression was associated with worse clinical outcomes and tumor-specific death in the TCGA-UM dataset. Based on the coefficients obtained from the Cox proportional hazard regression analysis, a CCL18-related prognostic signature formula was constructed as follows: risk score = 0.05590 × age +2.43437 × chromosome 3 status +0.39496 × ExpressionCCL18. Notably, in this formula, the normal chromosome 3 was coded as 0, whereas the chromosome 3 loss was coded as 1. Each patient was assigned to either low-risk or high-risk groups using the median cut-off in the training cohort. High-risk patients survived for a shorter time than low-risk patients. The time-dependent and multivariate receiver operating characteristic curves showed promising diagnostic efficacy. Multivariate Cox regression analysis demonstrated the potential of this CCL18-related signature as an independent prognostic indicator. These results were validated using the GSE22138 dataset. In addition, in both TCGA-UM and GSE22138 datasets, stratification of clinical correlations and survival analyses based on this signature indicated the involvement of clinical progression and survival outcome in UM. In the high-risk group, Gene Ontology analyses mainly indicated the enrichment of immune response pathways, such as the T cell activation, response to interferon-gamma, antigen processing and presentation, interferon-gamma-mediated signaling pathway, MHC protein complex, MHC class II protein complex, antigen binding, and cytokine binding. Meanwhile, Kyoto Encyclopedia of Genes and Genomes analyses showed enrichments of pathways in cancer, cell adhesion, cytokine-cytokine receptor interaction, chemokine signaling pathway, Th1 and Th2 cell differentiation, and chemokine signaling pathway. Moreover, single-sample gene set enrichment analysis demonstrated the enrichment of almost all immune cells and immune functions in the high-risk group. In summary, a new prognostic CCL18-related signature was successfully established using the TCGA-UM dataset and validated using the GSE22138 dataset with meaningful predictive and diagnostic efficacies. This signature could serve as an independent and promising prognostic biomarker for patients with UM.

Identification of a prognostic six-immune-gene signature and a nomogram model for uveal melanoma.

BACKGROUND: To identify an immune-related prognostic signature and find potential therapeutic targets for uveal melanoma. METHODS: The RNA-sequencing data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The prognostic six-immune-gene signature was constructed through least absolute shrinkage and selection operator and multi-variate Cox regression analyses. Functional enrichment analysis and single sample GSEA were carried out. In addition, a nomogram model established by integrating clinical variables and this signature risk score was also constructed and evaluated. RESULTS: We obtained 130 prognostic immune genes, and six of them were selected to construct a prognostic signature in the TCGA uveal melanoma dataset. Patients were classified into high-risk and low-risk groups according to a median risk score of this signature. High-risk group patients had poorer overall survival in comparison to the patients in the low-risk group (p < 0.001). These findings were further validated in two external GEO datasets. A nomogram model proved to be a good classifier for uveal melanoma by combining this signature. Both functional enrichment analysis and single sample GSEA analysis verified that this signature was truly correlated with immune system. In addition, in vitro cell experiments results demonstrated the consistent trend of our computational findings. CONCLUSION: Our newly identified six-immune-gene signature and a nomogram model could be used as meaningful prognostic biomarkers, which might provide uveal melanoma patients with individualized clinical prognosis prediction and potential novel treatment targets.

Clinical risk factors for peritoneal dialysis withdrawal at different dialysis duration.

BACKGROUND: The duration of patients maintained on peritoneal dialysis (PD) varied. This study investigated the clinical risk factors for PD withdrawal at different dialysis duration. METHODS: Patients who initiated PD from 1994 to 2011 were recruited and followed for at least 10 years until 2021. Patients were grouped into four groups according to dialysis duration or time on treatment (TOT) when withdrew PD. RESULTS: A cohort of 586 patients were enrolled (mean age of 54.9 years, median dialysis duration or TOT of 47.9 months). Patients who maintained PD for longer than 10 years were younger, with lower prevalence of diabetes, lower serum C-reactive protein (CRP) level and white blood cell (WBC) count, higher serum albumin and pre-albumin level, higher normalized protein catabolic rate (nPCR) and residual kidney function, and more common use of renin-angiotensin system inhibitors (RASi) at baseline (p < 0.05 for all). Peritonitis related death and ultrafiltration failure related HD transferring increased along with time on PD (p < 0.001). Old age, diabetes, low serum albumin, high WBC count, hypertensive nephropathy, and nonuse of RASi were associated with increased risk of non-transplantation related PD withdrawal (p < 0.05 for all). Low baseline CRP and use of RASi were independent predictors for long-term PD maintenance (p < 0.05 for all). CONCLUSIONS: Long-term PD patients demonstrated young age, low prevalence of diabetes, better nutrition status, absence of inflammation, better residual kidney function, and higher proportion of RASi usage at baseline. Absence of inflammation and use of RASi were independently associated with long-term PD maintenance.

Gene polymorphisms of VEGF and KDR are associated with initial fast peritoneal solute transfer rate in peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is an effective and successful renal replacement therapy. The baseline peritoneal solute transfer rate (PSTR) is related to local membrane inflammation and may be partially genetically determined. Herein, we focused on vascular endothelial growth factor (VEGF) and its receptor, kinase insert domain containing receptor (KDR). METHODS: This study recruited 200 PD patients from Renji Hospital in Shanghai, China. We analysed the association between the polymorphisms of VEGF and KDR and the 4-hour dialysate-to-plasma ratio for creatinine (4 h D/P Cr), which was measured between one and three months after initiating PD. RESULTS: The CC genotype in VEGF rs3025039 and the AA genotype in KDR rs2071559 were both positively associated with a fast baseline PSTR (VEGF rs3025039 CC vs. TT + TC: 0.65 ± 0.12 vs. 0.61 ± 0.11; P = 0.029; KDR rs2071559 AA vs. GA + GG: 0.65 ± 0.12 vs. 0.62 ± 0.12; P = 0.039). CONCLUSION: Baseline PSTR was partly determined by VEGF and KDR gene polymorphisms.

Self-care or assisted PD: development of a new approach to evaluate manual peritoneal dialysis practice ability.

BACKGROUND: Peritoneal dialysis (PD) is a home-based therapy which requires the patients or their caregivers to perform the practice. We aimed to develop a practical approach to evaluate PD practice ability of the patients and to identify berries to self-care PD. METHODS: A structural form was designed comprising measures of physical, cognitive, and operational abilities which were required to perform manual PD independently. The evaluation was jointly conducted by a PD nurse, a nephrologist and a close family member of the patient. Patients who met all the requirements were deemed as capable of performing PD independently (self-care PD) and others were deemed as needing an assistant (assisted PD). RESULTS: The evaluation form was applied in 280 prevalent PD patients and 33.9% of them were assessed as needing assisted PD, mainly due to physical (62.1%) or operational (66.3%) disabilities. The evaluation result was consistent with current dialysis status in 79.3% patients and it matched better in patients who performed PD with the help of an assistant (93.0 vs. 76.8%, p = 0.014). Patients who were evaluated as having barriers to self-care PD but still performed PD without an assistant were older and demonstrated higher prevalence of diabetic nephropathy and PD-related infection, lower education level, and lower serum albumin (p < 0.05). CONCLUSIONS: The PD practice ability assessment form is useful to identify patients with barriers to self-care PD. It provides objective information to the patients and their family to choose feasible PD practice modality, self-care, or assisted PD.

High EIF4E2 expression is an independent prognostic risk factor for poor overall survival and recurrence-free survival in uveal melanoma.

Uveal melanoma (UM), as the most common primary intraocular carcinoma, is a relatively rare but lethal tumor. Upregulated eukaryotic translation initiation factor 4E family member 2 (EIF4E2) promotes the progression of multiple human carcinomas. However, its role remains unclear in UM. To identify the prognostic value of EIF4E2 in UM, we downloaded RNA-sequencing data along with clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. EIF4E2 mRNA was significantly increased in three different subgroups in the TCGA-UM dataset. High mRNA expression was correlated with shorter overall survival (OS) and shorter recurrence-free survival (RFS). Moreover, we constructed a prognostic signature using Cox regression analyses in our training cohort TCGA-UM dataset as follows: risk score = 0.04335 × Age +0.49639 × expression of EIF4E2. Based on the risk score, each patient was classified as high-risk or low-risk. Additional survival analyses suggested that patients in the high-risk score group had an unfavorable OS compared with patients in the low-risk score group, which was validated in two external GEO datasets, including GSE84976 and GSE22138. Functional enrichment analysis demonstrated that UM was correlated with hypoxia-related functions. Gene set enrichment analysis (GSEA) indicated significant enrichments of the p53 and Notch pathways. In addition, EIF4E2 was genetically altered in 12.5% (10/80) of UM patients. Epigenetically, higher expression of cg03852847 was correlated with longer OS and longer RFS. In conclusion, our findings demonstrated that high EIF4E2 expression is an independent prognostic risk factor for UM patients. EIF4E2 might play an important role in hypoxia-related signaling pathways during UM progression. Both genetic and epigenetic alterations may contribute to UM pathogenesis. These findings could offer individualized clinical prognostication and potential novel treatment targets for UM patients.

Peritoneal Dialysis as an Option for Unplanned Dialysis Initiation in Patients with End-Stage Renal Disease and Diabetes Mellitus.

AIMS: This study aimed to compare the short-term complications and long-term prognosis between urgent-start peritoneal dialysis (PD) and hemodialysis (HD), and explore the safety and feasibility of PD in end-stage renal disease (ESRD) patients with diabetes. METHODS: This retrospective study enrolled ESRD patients with diabetes who required urgent-start dialysis at a single center from January 2011 to December 2014. Short-term (30-day) dialysis-related complications and patient survival trends were compared between patients receiving PD and HD. RESULTS: Eighty patients were included in the study, including 50 (62.5%) who underwent PD. The incidence of dialysis-related complications and complications requiring reinsertion during the first 30 days was significantly lower in PD patients. Logistic regression identified urgent-start HD as an independent risk factor for dialysis-related complications compared with urgent-start PD. The patient survival rate was higher in the PD compared to that in the HD group. CONCLUSIONS: PD may be acceptable, safe, and feasible for urgent-start dialysis in ESRD patients with diabetes.

YY1 promotes IL-6 expression in LPS-stimulated BV2 microglial cells by interacting with p65 to promote transcriptional activation of IL-6.

Neuroinflammation plays a critical role in the process of neurodegenerative disorders, during which microglia, the principal resident immune cells in the central nervous system, are activated and produce proinflammatory mediators. Yin-Yang 1 (YY1), a multi-functional transcription factor, is widely expressed in cells of the immune system and participate in various cellular processes. However, whether YY1 is involved in the process of neuroinflammation is still unknown. In the present study, we found that YY1 was progressively up-regulated in BV2 microglial cells stimulated with lipopolysaccharide (LPS), which was dependent on the transactivation function of nuclear factor kappa B (NF-κB). Furthermore, YY1 knockdown notably inhibited LPS-induced the activation of NF-κB signaling and interleukin-6 (IL-6) expression in BV-2 cells, but not mitogen-activated protein kinase (MAPK) signaling. Moreover, YY1 strengthened p65 binding to IL-6 promoter by interacting with p65 but decreased H3K27ac modification on IL-6 promoter, eventually increasing IL-6 transcription. Taken together, these results for the first time uncover the regulatory mechanism of YY1 on IL-6 expression during neuroinflammation responses and provide new lights into neuroinflammation.

Yin Yang 1 Dynamically Regulates Antiviral Innate Immune Responses During Viral Infection.

BACKGROUND/AIMS: Type I interferon (IFN-1) production and IFN-1 signaling play critical roles in the host antiviral innate immune responses. Although transcription factor Yin Yang 1 (YY1) has been reported to have a dual activator/repressor role during the regulation of interferon beta (IFN-ß) promoter activity, the roles of YY1 in the regulation of upstream signaling pathways leading to IFN-1 induction and IFN-1 signaling during viral infection remain to be elucidated. METHODS: The roles of YY1 in IFN-1 production and IFN-1 signaling were investigated using immunoblotting, real-time PCR, small interfering RNA (siRNA)-mediated YY1 knockdown, YY1 overexpression by transient transfection, and co-immunoprecipitation, using mouse cells. RESULTS: YY1 was shown to interact with STAT1 in the absence of viral infection. Following viral infection, YY1 protein expression levels were decreased. YY1 knockdown led to a considerable downregulation of phosphorylated (p) TBK1 and pIRF3 expressions, while YY1 overexpression significantly upregulated pTBK1 and pIRF3 expression levels and promoted virus-induced IFN-ß production. Additionally, YY1 knockdown led to a significant upregulation of pSTAT1, pSTAT2 and antiviral interferon-stimulated genes, and inhibited viral replication. CONCLUSION: We demonstrated here that YY1 interacts with STAT1 and dynamically regulates the induction of IFN-1 production and activation of IFN-1 signaling in different stages during viral infection.

Hyperleptinaemia, insulin resistance and survival in peritoneal dialysis patients.

AIM: The aim of this study was to clarify the relationship between insulin resistance (IR) and glucose and lipid metabolism in peritoneal dialysis (PD) patients. The study also investigated the prognostic factors for survival in long-term peritoneal dialysis patients. METHODS: Participants were recruited from July 1 to August 1, 2011, based on selection criteria. Patients were divided into two groups, high (H) and low (L) group according to the median value of homeostasis model assessment of IR (HOMA-IR). Type 2 diabetes mellitus (DM) patients were chosen as positive controls. Clinical, plasma biochemical and metabolic parameters were observed and recorded at the outset and follow-up of this study. Mortality related factors were also detected, and statistical analyses were performed. RESULTS: A total of 157 cases with an average age of 55 ± 15 years were included. There were 26, 66 and 65 cases in the DM, H and L groups, respectively. Younger age, lower body mass index, high sensitive C-reactive protein (hsCRP) level, higher normalized protein catabolic rate (nPCR) were found in the L group compared with the other two groups. HOMA-IR positively correlated with age, leptin and triglyceride levels, and it negatively correlated with BMI. L group had better survival rate than H and DM groups. Dialysis duration, serum leptin level, nPCR and hsCRP were statistically associated with mortality. CONCLUSION: Insulin resistance may play an important role in the pathophysiology of glucose and lipid metabolism. Dialysis duration, leptin, nPCR and hsCRP may be risk factors for mortality in PD patients.

Research hotspots and development trends in volume management of peritoneal dialysis patients: a bibliometrics and visual analysis up to 2022.

OBJECTIVES: Among different renal replacement therapies (RRTs), peritoneal dialysis (PD) is a family based treatment method with multiple advantages, which allowing patients to maintain autonomy, avoiding frequent hospital visits, and preventing the spread of the disease virus. To visually analyze the literatures related to volume management of PD patients through bibliometric methods, to explore research hotspots and development trends in this field. METHODS: The relevant literatures of PD patient volume management in the Web of Science core collection database were retrieved with the terms of peritoneal dialysis, volume management, capacity management, fluid status, and volume overload. The retrieval time was from the establishment of the database to October 2022. CiteSpace 6.1.R3 software was used to visually analyze Country, Institution, Author, Keyword, and draw keyword clusters and keyword emergence maps. RESULTS: A total of 788 articles were included in the analysis, and the annual number of papers was on the rise, with the American, China, and Brirain in the top three, and Peking University and University College London in the top. Keywords cluster analysis showed 11 clusters. In the keyword emergence analysis, the keywords with higher emergence intensity rank are continuous cyclic peritoneal dialysis, ambulatory peritoneal dialysis, and icodextrin. The current research hotspots and trends are in the evaluation of peritoneal dialysis patients' volume status, the selection and adjustment of dialysis prescriptions, and adverse health outcomes. CONCLUSION: The research on peritoneal dialysis volume management in China started late, but it has developed rapidly, and has a firm grasp of current research hotspots. However, there is less cooperation with other countries, so international exchanges and cooperation should be strengthened. At present, the volume assessment methods and dialysis modes are still the research hotspots, paying more attention to the adverse health outcomes of patients.

Automated peritoneal dialysis as a cost-effective urgent-start dialysis option for ESRD patients: A prospective cohort study.

BACKGROUND: Several studies have reported the feasibility of urgent-start peritoneal dialysis (PD) as an alternative to hemodialysis (HD) using a central venous catheter (CVC). However, the cost-effectiveness of automated peritoneal dialysis (APD) as an urgent-start dialysis modality has not been directly evaluated, especially in China. METHODS: We prospectively enrolled patients with end-stage renal disease (ESRD) who required urgent-start dialysis at a single center from March 2019 to November 2020. Patients were grouped according to their urgent-start dialysis modality (APD and HD). Urgent-start dialysis conducted until 14 days after PD catheter insertion. Then, PD was maintained. Each patient was followed until July 2021 or death or loss to follow-up. The primary outcome was the incidence of short-term dialysis-related complications. The secondary outcome was the cost and duration of the initial hospitalization. Technique survival, peritonitis-free or bacteriamia-free survival and patient survival were also compared. RESULTS: Sixty-eight patients were included in the study, of whom 36 (52.9%) patients were in APD group. Mean follow-up duration was 20.1 months. Compared with the HD group, the APD group had significantly fewer short-term dialysis-related complications. The cost of initial hospitalization was also significantly lower in APD patients. There was no significant difference between APD and HD patients with respect to duration of the initial hospitalization, technique survival rate, peritonitis-free or bacteriemia-free survival rate, and patient survival rate. CONCLUSION: Among ESRD patients with an urgent need for dialysis, APD as urgent-start dialysis modality, compared with HD using a CVC, resulted in fewer short-term dialysis-related complications and lower cost.

Physical performance and health-related quality of life among older adults on peritoneal dialysis: a cross-sectional study.

PURPOSE: Identifying performance-based tests that meaningful for patients may facilitate the implementation of rehabilitation programs. The primary aim of this study was to determine the independent associations between different performance-based tests and health-related quality of life (HRQoL) among elderly peritoneal dialysis (PD) patients. METHODS: This cross-sectional study was conducted in China. Patients on PD who were 60 years of age or above were included. HRQoL was assessed using the Medical Outcomes Study Short Form 36. Physical function was determined by handgrip strength, timed up and go (TUG) test, 5-repetition sit-to-stand test, and comfortable gait speed. Depressive symptoms were measured using the self-reported Geriatric Depression Scale (GDS-15). Multiple linear regression analyses were performed to examine the factors influencing HRQoL. RESULTS: In total, 115 participants with a mean age of 69.7 were included (46 women and 69 men). TUG (ß =- 0.460, p < 0.001), prealbumin (ß = 0.223, p = 0.014), and education level (ß = 0.183, p = 0.042) were associated with physical health. GDS score (ß = - 0.475, p < 0.001), serum albumin level (ß = 0.264, p = 0.003), and sex (ß = 0.217, p = 0.012), were associated with mental HRQoL. CONCLUSION: TUG could be a valuable test for use in clinical practice and research aiming at facilitating tailed exercise programs, as it was associated with self-perceived physical HRQoL and could be meaningful to elderly PD patients. Depressive symptoms and nutrition were another two important rehabilitation areas for optimizing the overall HRQoL of older adults on PD.

Clinical characteristics associated with the properties of gut microbiota in peritoneal dialysis patients.

BACKGROUND: Gut microbiota alters in patients with end-stage renal disease, which contributes to inflammation, atherosclerosis, and results in increased incidence of cardiovascular diseases. The present study investigated the potential clinical factors, which influence the gut microbial structure and function in patients undergoing peritoneal dialysis (PD). METHODS: This is a cross-sectional study performed in 81 prevalent PD patients. Gut microbiota was assessed by high throughput sequencing of 16S ribosomal ribonucleic acid gene in fecal samples. Gas chromatography was conducted to measure stool short-chain fat acid (SCFA) concentrations. Demographic parameters and clinical characteristics, including dialysis regimen, residual renal function, nutrition, and inflammation, were retrieved and related to the properties of gut microbiota. RESULTS: PD duration, peritoneal glucose exposure, and estimated glomerulus filtration rate (eGFR) were identified to be associated with microbial variations. Significant separation of microbial composition was shown between patients with short or long PD duration (p = 0.015) and marginal differences were found between patients grouped by different levels of peritoneal glucose exposure (p = 0.056) or residual renal function (p = 0.063). A couple of gut bacteria showed different abundance at amplicon sequencing variant level between these patient groups (p < 0.05). In addition, stool isobutyric and isovaleric acid concentrations were significantly reduced in patients with longer dialysis duration, higher peritoneal glucose exposure, or declined eGFR (p < 0.05). CONCLUSIONS: This pilot study demonstrated that long dialysis duration, high peritoneal glucose exposure, and loss of residual renal function were associated with gut microbiota alteration and reduced branched-chain SCFA production in PD patients.

Daily peritoneal ultrafiltration predicts patient and technique survival in anuric peritoneal dialysis patients.

BACKGROUND: Maintenance dialysis therapy is the only way to remove excess fluid in patients with anuric end-stage renal disease. The optimal ultrafiltration (UF) volume in patients on peritoneal dialysis (PD) remains controversial. METHODS: We retrospectively analysed a cohort of 86 prevalent anuric PD patients followed up for a median of 25.3 months (range, 6 to 54 months). Clinical and PD parameters were recorded yearly. Kaplan-Meier analysis and Cox proportional hazards models were used to identify risk factors of mortality and technique failure in patients with a UF >/=1 L/24 h or <1 L/24 h. RESULTS: When compared to those with a UF <1 L/24 h, patients with a UF >/=1 L/24 h had significantly higher haemoglobin levels (101.9 +/- 20.5 vs 89.3 +/- 20.2 g/L, P < 0.05) and tended to be younger (55.0 +/- 12.5 vs 60.6 +/- 16.1 years, P = 0.10). Also, while Kt/V and CCr were stable over time, UF decreased significantly over the study period (baseline, 1205.5 +/- 327.3 ml/24 h vs after 3 years, 870.6 +/- 439.8 ml/24 h; P < 0.001). Using Kaplan-Meier analysis, patients with baseline UF <1 L/24 h had significantly worse outcome (survival, 27.2 +/- 3.9 vs 42.4 +/- 1.9 months; P < 0.001). In multivariate Cox regression analysis, age, time-dependent UF volume and serum albumin were independent predictors of mortality, while UF independently predicted technique failure. CONCLUSIONS: The present study demonstrates a strong predictive value of daily peritoneal UF for both technique and patient survival in prevalent anuric PD patients. Identifying markers of satisfactory fluid status, as well as optimizing therapy to meet UF goals, remains an important clinical target.

Family caregiver's burden and the social support for older patients undergoing peritoneal dialysis.

BACKGROUND: Most elderly people undergoing peritoneal dialysis (PD) treatment have a high incidence of frailty, cognitive impairment and emotional disturbance leading to a significant impact on families. The burden experienced by the family caregivers could affect their physical and emotion health. The objective of this study was to examine the level of burden on family caregivers of elderly adults receiving PD and to identify any contributing factors. MATERIALS AND METHODS: This was a cross-sectional study employing convenience sampling. Patient-caregiver dyads were recruited from the outpatient clinic of a university hospital in China in 2019. Caregivers provided information on their perceived burden and health-related quality of life. The elderly patients reported their functional dependence and depressive symptoms in the same interview. Linear regression analyses were used to determine the factors contributing to caregivers' burden. RESULTS: Sixty patient-caregiver dyads were recruited. The patients had a mean age of 70.7 ± 7.4 years. The caregivers reported moderate levels of burden having ZBI score of 30.5 ± 15.9. Multivariate analyses showed that being female, perceiving one's financial status as insufficient, a low level of social support for the caregiver, depressive symptoms in the patients and disability in carrying out the instrumental activities of daily life were statistically significant predictors of caregiver burden (adjusted R2 = 0.46, p < 0.001). CONCLUSION: Elderly adults receiving PD who experience physical dependence and depressive symptoms are a burden for caregivers. In response to this challenge, interventions designed with the goal of supporting the emotional and mental wellbeing of caregivers are warranted.

YY1/LncRNA GAS5 complex aggravates cerebral ischemia/reperfusion injury through enhancing neuronal glycolysis.

Yin-Yang 1 (YY1) has been identified as playing critical roles in multiple diseases. However, little is known regarding its roles and mechanisms in cerebral ischemia/reperfusion (I/R) injury. This study is aimed to explore the roles of YY1 in regulating neuronal apoptosis in cerebral I/R injury and its underlying mechanisms. Primary mouse cerebral cortical neurons were isolated and subjected to OGD/R to mimic cerebral I/R injury in vitro. The roles of YY1 on OGD/R-induced neuronal injury were investigated by performing western blotting, quantitative real-time polymerase chain reaction, TUNEL, RNA-binding protein immunoprecipitation, chromatin immunoprecipitation, chromatin isolation by RNA purification assay, glucose uptake assay, lactate production assay, and extracellular acidification rate assay. YY1-binding long non-coding RNAs (LncRNAs) in neurons subjected to OGD/R were identified by RIP and RNA sequencing. The roles of YY1 on cerebral I/R in vivo were detected by assessing neuronbehaviour, infarct size, and neuronal apoptosis. We found that YY1 expression is downregulated, and LncRNA GAS5 is upregulated in neurons subjected to OGD/R. OGD/R treatment promotes YY1 interacting with GAS5 in neurons, and YY1 negatively regulates GAS5 expression by binding to GAS5 promoter to repress its transcription. Besides, YY1 and GAS5 bind to the same region of PFKFB3 promoter to promote PFKFB3 expression and strengthen neuronal glycolysis, resulting in aggravating OGD/R-induced neuronal apoptosis. Knockdown of YY1 or GAS5 protects against I/R-induced ischemic brain damage and improves overall neurological functions in vivo. Overall, YY1 interacts with LncRNA GAS5 to promote PFKFB3 transcription to enhance neuronal glycolysis, resulting in aggravating cerebral I/R injury.

Curcumin protects neural cells against ischemic injury in N2a cells and mouse brain with ischemic stroke.

Background and Purpose: Curcumin, a natural antioxidant isolated from Curcuma longa, has been reported to exert neuroprotective effect in animal models of ischemic stroke. However, the underlying mechanism is still not fully understood. The purpose of this study was to investigate the effect of curcumin treatment on neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion (I/R) injury and in mouse N2a cells after oxygen-glucose deprivation/reoxygenation (OGD/R) injury and its underlying mechanism. Methods: The cerebral I/R injury was established by 1-hr middle cerebral artery occlusion (MCAO) and reperfusion in mice. Infarct volume was determined by TTC staining, and neurological score was evaluated by mNSS. Cell morphology in the ischemic boundary zone were detected by HE staining. The number and apoptotic rate of neurons in ischemic boundary zone were assayed by immunohistochemistry and TUNEL, respectively. Mouse neuroblastoma N2a cells were subjected to OGD/R. Cell viability was assessed with CCK-8. The mitochondrial membrane potential was measured using JC-1 staining. The expression of Bax, Bcl-2, and caspase-3 was detected using Western blotting. Besides, cellular distribution of Bax was determined by immunofluorescence assays. Results: Curcumin treatment reduced infarct volume, improved neurological function, alleviated the morphological damage of neurons, and increased neuronal survival rate after I/R injury in vivo. Moreover, curcumin treatment improved cell viability, reduced cell apoptosis, increased Bcl-2 protein levels while decreased Bax and caspase-3 expressions in mouse N2a cells after OGD/R injury. Besides, curcumin treatment inhibited Bax activation and maintained mitochondrial membrane integrity. Conclusion: Curcumin promotes neuron survival in vivo and in vitro to exert neuroprotective effects against ischemia injury. Moreover, our results for the first time demonstrated curcumin inhibited ischemia-induced mitochondrial apoptosis via restricting Bax activation, which may be one of the possible mechanisms underlying the neuroprotective effects of curcumin.

The role of hemoglobin variability as a prognostic indicator in peritoneal dialysis patients: a retrospective descriptive study.

PURPOSE: To investigate the effect of hemoglobin fluctuations on cardiovascular prognosis of patients on peritoneal dialysis (PD). METHODS: Retrospective descriptive study, with sample composed of 333 patients treated with PD at the Renal Unit. Two indicators were adopted to indicate hemoglobin fluctuations of PD patients: absolute value of hemoglobin variability (HV) and HV trend. Moreover, the new cardiovascular events and recurrent rate of cardiovascular events within 3 months after PD were recorded and were compared in groups of PD patients classified by hemoglobin fluctuation indicators. RESULTS: Patients whose HV value is less than 10 g/l have an increased risk of new cardiovascular events than patients with HV value > 10 g/l (27.2 vs. 12.2%, p < 0.05) during 3 months after PD. Patients who kept high hemoglobin values (≥ 110 g/l) 3 months after PD are prone to develop recurrent cardiovascular events than patients with relatively low hemoglobin values (< 110 g/l; p < 0.05). CONCLUSIONS: Hemoglobin fluctuations were associated with the cardiovascular prognosis in patients on PD. A limitation of our study is its retrospective design. However, the results in this research indicated anemia in PD patients without cardiovascular events history should be timely treated. Instead, hemoglobin should be kept within a relatively low level in patients with history of cardiovascular events. Additional clinical researches are needed to verify and improve our findings.

HIV-1 diversity in infected individuals in Suzhou and Suqian, China.

Jiangsu is one province with severe HIV-1 epidemic in China. However, the molecular epidemiological characterizations of HIV-1 in many cities of Jiangsu remain unclear. A molecular epidemiological investigation was performed based on 38 HIV-positive samples collected from Suzhou and Suqian during 2011-2013. Five HIV-1 genomic fragments, p17, pol, vif-vpr, vpr-env, and C2V3 were amplified and sequenced from these samples. HIV-1 group M subtype of each sample was determined by phylogenetic analyses with the standard reference sequences. Among these infected individuals, 81.6 % (31/38) self-reported to be infected via sexual contacts, including 50.0 % (19/38) via heterosexual contact and 31.6 % (12/38) via homosexual contact. Among 34 samples with available pol or vif-env sequence, 19 (55.9 %) CRF01_AE, 7 (20.6 %) CRF07_BC, 3 (8.8 %) CRF08_BC, and 5 (14.7 %) inter-subtype recombinants were identified. No pure B, B' and C subtypes were found in this cohort. The five recombinants contain one B/C, three CRF01/B and one CRF01/B/C recombinants. These results suggest that CRF01_AE was the most predominant HIV-1 group M subtype and CRF01_AE-involved recombinants were the major recombinant forms. Comparison showed that there was no obvious difference in HIV-1 group M subtype distribution between Jiangsu (including Suzhou and Suqian) and the surrounding provinces (e.g., Shanghai, Anhui, and Shandong). CRF01_AE and CRF07_BC were the top two predominant HIV-1 genotypes in Jiangsu, and less and/or no pure subtype B and C was currently circulating here. We predicted that more CRF01/CRF07 recombinants, but fewer B/C recombinants will be generated in Jiangsu in future.