Identification of differentially expressed genes in diabetic kidney disease by RNA-Seq analysis of venous blood platelets.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. However, because of shared complications between DKD and chronic kidney disease (CKD), the description and characterization of DKD remain ambiguous in the clinic, hindering the diagnosis and treatment of early-stage DKD patients. Although estimated glomerular filtration rate and albuminuria are well-established biomarkers of DKD, early-stage DKD is rarely accompanied by a high estimated glomerular filtration rate, and thus there is a need for new sensitive biomarkers. Transcriptome profiling of kidney tissue has been reported previously, although RNA sequencing (RNA-Seq) analysis of the venous blood platelets in DKD patients has not yet been described. In the present study, we performed RNA-Seq analysis of venous blood platelets from three patients with CKD, five patients with DKD and 10 healthy controls, and compared the results with a CKD-related microarray dataset. In total, 2097 genes with differential transcript levels were identified in platelets of DKD patients and healthy controls, and 462 genes with differential transcript levels were identified in platelets of DKD patients and CKD patients. Through Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, we selected 11 pathways, from which nine potential biomarkers (IL-1B, CD-38, CSF1R, PPARG, NR1H3, DDO, HDC, DPYS and CAD) were identified. Furthermore, by comparing the RNA-Seq results with the GSE30566 dataset, we found that the biomarker KCND3 was the only up-regulated gene in DKD patients. These biomarkers may have potential application for the therapy and diagnosis of DKD, as well aid in determining the mechanisms underlying DKD.

Additional hemoperfusion is associated with improved overall survival and self-reported sleep disturbance in patients on hemodialysis.

INTRODUCTION: Patients with maintenance hemodialysis have experienced long-standing sleep disturbance. In this study, we attempted to explore whether long-term hemoperfusion could improve sleep and increase the overall survival in hemodialysis patients. METHODS: A total of 158 patients, who underwent routine hemodialysis, were assessed in this study. These patients were computer-matched into two groups, with one group including 80 patients with absolute hemodialysis and the other consisting of 78 cases with hemodialysis in combination with hemoperfusion. Hemoperfusion was performed 1-2 times biweekly, with each session lasting 2 h. Self-reported sleep disturbance was evaluated before and after the observational time (2-year period); sleep quality was measured using the Pittsburgh Sleep Quality Index. FINDINGS: Using multivariate regression analyses, we found sleep duration was associated with age, diabetes, low income, pruritus, hyperphosphatemia, hypercalcemia, high parathyroid hormone, and hemoglobin (P < 0.001). The overall survival rate of the hemodialysis in combination with hemoperfusion group was significantly higher than that of the absolute hemodialysis group (P < 0.05) after adjusting for sex, age, and diabetes. A 2-year hemoperfusion therapy was associated with improved sleep disturbance and sleep efficiency; this was accompanied by an increase in nocturnal melatonin levels. Furthermore, there was a significant difference in the first hospitalization between the hemodialysis and hemodialysis in combination with hemoperfusion groups (P < 0.01). DISCUSSION: Our results indicated that hemoperfusion in combination with hemodialysis is associated with an increase in the overall survival and improved sleep disorders in hemodialysis patients.

Association of sleep disorders, chronic pain, and fatigue with survival in patients with chronic kidney disease: a meta-analysis of clinical trials.

OBJECTIVE: Sleep disorders, chronic pain, and fatigue have been long-standing torments in most patients with chronic kidney disease (CKD). In this review, we attempted to explore whether these nontraditional cardiovascular risk factors are associated with increased mortality in patients with CKD. METHOD: Electronic searches were performed in MEDLINE (PubMed, 1966-2018), EMBASE (1974-2018), ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases. All prospective or retrospective studies were considered eligible if they were cohort or observational studies and the final outcome was all-cause death or mortality. RESULTS: We ultimately included 18 studies (12 studies on sleep disorders, three studies on chronic pain, and three studies on fatigue) in our review. Pooled analysis of all studies indicated that patients with sleep disorders, chronic pain, and fatigue had increased risks of all-cause mortality (risk ratio [RR] = 1.47, 95% confidence interval [CI] = 1.30-1.66, p < 0.0001; RR = 1.29, 95% CI = 1.27-1.31, p < 0.0001; RR = 1.45, 95% CI = 1.23-1.70, p < 0.0001, respectively). Pooled results from four studies indicated that dialysis patients with sleep-disordered breathing had increased cardiovascular disease outcomes (RR = 2.45, 95% CI = 1.74-3.44, p < 0.0001). CONCLUSION: Sleep disorders, chronic pain, and fatigue are remarkably associated with increased all-cause mortality in patients with CKD. Large clinical randomized controlled trials are required to further confirm the results of our meta-analysis.

Association of lean body mass with nutritional parameters and mortality in hemodialysis patients: A long-term follow-up clinical study.

OBJECTIVE: This study aimed to evaluate the correlation between lean body mass (LBM) and nutritional status in hemodialysis (HD) patients to better predict their long-term prognosis. METHODS: Anthropometric body measurements and biochemical parameters were recorded from 222 patients on maintenance hemodialysis (MHD) at the Shanghai Pudong Hospital Hemodialysis Center. LBM was calculated using the serum creatinine index (LBM-SCR), mid-arm muscle circumference (LBM-MAMC), and dominant-arm hand-grip strength (LBM-HGS). Patient mortality and hospitalization were observed after 24 months. RESULTS: LBMs measured from LBM-SCR and LBM-MAMC were associated with sex, body mass index (BMI), serum albumin, and serum creatinine (SCR) ( p < 0.05). Through three methods of LBM evaluation, low LBM was shown to be associated with a higher mortality in patients undergoing HD ( p < 0.05). In addition, the rate of hospitalization among these patients was significantly increased ( p < 0.05). Performing multivariate regression analysis using mortality and hospitalization as the dependent variable, we found LBM-SCR and LBM-HGS are strongly associated with hospitalization and mortality in HD patients, indicating LBM is an important factor in prediction of outcomes in those patients. CONCLUSION: LBM is associated with nutritional parameters in HD patients, and LBM-SCR, HGS, and MAMC are simple approaches for accurately predicting the patient's risk of hospitalization and/or death.

Epigallocatechin gallate protects against homocysteine-induced vascular smooth muscle cell proliferation.

Epigallocatechin gallate (EGCG), a bioactive ingredient of green tea, plays a protective role in the cardiovascular system. Homocysteine (Hcy) is a major risk factor for chronic kidney disease and cardiovascular disease. The present study aimed to investigate the role of EGCG in Hcy-induced proliferation of vascular smooth muscle cells (VSMCs) and its underlying mechanism. We also explored the roles of rennin-angiotensin system (RAS), extracellular signal-regulated kinases (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK) in this process. Human aortic smooth muscle cells (HASMCs) were treated with different drugs for different periods. The proliferation rate of HASMCs was detected using the CCK-8 and BrdU labeling assays. The Western blot assay was used to determine the expression levels of angiotensin II type 1 receptor (AT-1R), ERK1/2, and p38 MAPK. Compared with the control group, the HASMCs treated with Hcy at different doses (100, 200, 500, and 1000 µM) showed significantly increased proliferation. Hcy increased the expression of AT-1R, whereas EGCG decreased the protein expression of AT-1R. Furthermore, we found that Hcy-induced expression of p-ERK1/2 and p-p38MAPK was dependent on AT-1R. Compared with Hcy (500 µM)-treated cells, EGCG (20 µM)-treated cells showed decreased proliferation as well as expression of AT-1R, p-ERK1/2, and p-p38MAPK. In addition, HASMC proliferation was suppressed by the addition of an AT-1R blocker (olmesartan), an ERK1/2 inhibitor (PD98059), and a p38MAPK inhibitor (SB202190). EGCG can inhibit AT-1R and affect ERK1/2 and p38MAPK signaling pathways, resulting in the decrease of VSMC proliferation induced by Hcy.

Epigallocatechin-3-gallate Attenuates Renal Damage by Suppressing Oxidative Stress in Diabetic db/db Mice.

Epigallocatechin-3-gallate (EGCG), extracted from green tea, has been shown to have antioxidative activity. In the present study, we evaluated the effect of EGCG on the kidney function in db/db mice and also tried to investigate the underlying mechanism of the renoprotective effects of EGCG in both animals and cells. EGCG treatment could decrease the level of urinary protein, 8-iso-PGF2a, and Ang II. Moreover, EGCG could also change the level of several parameters associated with oxidative stress. In addition, the protein expression levels of AT-1R, p22-phox, p47-phox, p-ERK1/2, p-p38 MAPK, TGF-ß1, and α-SMA in diabetic db/db mice were upregulated, and all of these symptoms were downregulated with the treatment of EGCG at 50 and 100 mg/kg/d. Furthermore, the pathological changes were ameliorated in db/db mice after EGCG treatment. HK-2 cell-based experiments indicated that EGCG could inhibit the expression of MAPK pathways, which is the downstream effector of Ang II mediated oxidative stress. All these results indicated that EGCG treatment could ameliorate changes of renal pathology and delay the progression of DKD by suppressing hyperglycemia-induced oxidative stress in diabetic db/db mice.

Laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension.

Since the first laparoscopic splenectomy (LS) was reported in 1991, LS has become the gold standard for the removal of normal to moderately enlarged spleens in benign conditions. Compared with open splenectomy, fewer postsurgical complications and better postoperative recovery have been observed, but LS is contraindicated for hypersplenism secondary to liver cirrhosis in many institutions owing to technical difficulties associated with splenomegaly, well-developed collateral circulation, and increased risk of bleeding. With the improvements of laparoscopic technique, the concept is changing. This article aims to give an overview of the latest development in laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension. Despite a lack of randomized controlled trial, the publications obtained have shown that with meticulous surgical techniques and advanced instruments, LS is a technically feasible, safe, and effective procedure for hypersplenism secondary to cirrhosis and portal hypertension and contributes to decreased blood loss, shorter hospital stay, and less impairment of liver function. It is recommended that the dilated short gastric vessels and other enlarged collateral circulation surrounding the spleen be divided with the LigaSure vessel sealing equipment, and the splenic artery and vein be transected en bloc with the application of the endovascular stapler. To support the clinical evidence, further randomized controlled trials about this topic are necessary.

Effect of prolonged weekly hemodialysis on survival of maintenance hemodialysis patients: a meta-analysis of studies.

OBJECTIVE: Use of prolonged nocturnal or daytime hemodialysis (PHD, more than 12 h per week) is associated with improvement of some clinical parameters relative to conventional hemodialysis (CHD, 4 h sessions, thrice weekly), but the effect on survival is unclear. The purpose of this meta-analysis is to determine whether PHD improves survival of patients undergoing maintenance HD. DESIGN: Systematic review of observational studies by meta-analysis. DATA SOURCES: Electronic searches in MEDLINE (PubMed, 1966-2012), EMBASE (1974-2012), www.clinicaltrials.gov, and the Cochrane Controlled Clinical Trials Register Database. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: All prospective or retrospective studies were considered eligible if they were cohort studies or observational studies that compared CHD with PHD (more than 12 h of HD per week due to more HD sessions or increased duration of HD sessions) and the final outcome was all-cause death or mortality. RESULTS: Thirteen studies with a total of 85,722 participants (10,285 PHD patients, 75,437 CHD patients) met the inclusion criteria. Summary estimates indicated that PHD was associated with decreased risk of mortality (OR = 0.72, 95% CI 0.64-0.81, p < 0.00001). Analysis of residual confounders of pooled results from six retrospective studies indicated that PHD patients were less likely to have low hemoglobin (11.7 vs. 11.2 g/dl, p < 0.01), younger (51.2 vs. 58.8 years, p < 0.01), less likely to have diabetes (27.1 vs. 40.8%, p < 0.01), and less likely to use a catheter (18.4 vs. 27.1%, p < 0.01), so these may have affected the outcome measure in these studies. CONCLUSIONS: PHD is associated with improved survival relative to CHD, although residual confounders have affected this relationship in observational studies. Large, multicenter randomized, controlled trials are needed to confirm our results.

Progesterone alleviates neural behavioral deficits and demyelination with reduced degeneration of oligodendroglial cells in cuprizone-induced mice.

Demyelination occurs widely in neurodegenerative diseases. Progesterone has neuroprotective effects, is known to reduce the clinical scores and the inflammatory response. Progesterone also promotes remyelination in experimental autoimmune encephalomyelitis and cuprizone-induced demyelinating brain. However, it still remains unclear whether progesterone can alleviate neural behavioral deficits and demyelination with degeneration of oligodendroglial cells in cuprizone-induced mice. In this study, mice were fed with 0.2% cuprizone to induce demyelination, and treated with progesterone to test its potential protective effect on neural behavioral deficits, demyelination and degeneration of oligodendroglial cells. Our results showed noticeable alleviation of neural behavioral deficits following progesterone treatment as assessed by changes in average body weight, and activity during the open field and Rota-rod tests when compared with the vehicle treated cuprizone group. Progesterone treatment alleviated demyelination as shown by Luxol fast blue staining, MBP immunohistochemical staining, and electron microscopy. There was an obvious decrease in TUNEL and Caspase-3-positive apoptotic cells, and an increase in the number of oligodendroglial cells staining positive for PDGFRα, Olig2, Sox10 and CC-1 antibody in the brains of cuprizone-induced mice after progesterone administration. These results indicate that progesterone can alleviate neural behavioral deficits and demyelination against oligodendroglial cell degeneration in cuprizone-induced mice.

[Efficacy analysis of laparoscopic sleeve gastrectomy in the treatment of obesity-related comorbidities].

OBJECTIVE: To investigate the safety and efficacy of laparoscopic sleeve gastrectomy (LSG) for the treatment of obesity and related diseases. METHODS: Clinical data of 67 patients who underwent LSG between December 2006 and July 2011 were analyzed retrospectively. Improvements in body mass index(BMI), percentage of excess weight loss(EWL), type 2 diabetes mellitus, hypertension and other comorbidities were observed at one year postoperatively. RESULTS: Laparoscopic procedures were completed in 67 patients without conversion. The operative time was(78±17) min. The postoperative hospital stay was(5.0±1.7) d. The postoperative recovery was uneventful and there were no perioperative death or severe postoperative complication. Sixty-four patients(95.5%) had a postoperative follow up of 1 year. One year after LSG, BMI decreased by(10.4±3.7) kg/m(2) from (37.7±4.1) kg/m(2) preoperatively and EWL was(80.2±27.7)%. In 13 cases of type 2 diabetes mellitus, 7 patients (53.8%, 7/13) were weaned off hypoglycemic agents or insulin. In 11 cases of hypertension, 5 required no medications(45.5%, 5/11). The remission rate was both 100%. There was significant resolution or improvement of other obesity-related comorbidiities, including hyper-triglyceridemia(n=51), hyperuricemia(n=42), sleep apnea syndrome (n=2), osteoarticular disease (n=9), and acanthosis (n=8). CONCLUSIONS: LSG is safe and feasible for the treatment of obesity and can cure or improve type 2 diabetes mellitus, hypertension and other obesity related comorbidities.

Developmental changes and subcellular location in inhibitor of DNA binding 2 (Id2) immunoreactivity in the rat Corpus callosum.

The mechanisms underlying oligodendrocyte differentiation and myelination are still unclear, but understanding them will be critical for the development of therapies for multiple sclerosis. Inhibitor of DNA binding 2 (Id2) is a transcription factor thought to inhibit oligodendrocyte differentiation, however, it is not known whether the developmental changes and subcellular localization of Id2 are related to myelination. Therefore, we investigated the developmental changes in and the subcellular localization of Id2 immunoreactivity in the rat Corpus callosum, at post-natal developmental stages P0, P7, P14, P21, P42 and P90, by immunohistochemistry. Id2 expression increased from P0 to a peak at P42, the late stage of myelination in the Corpus callosum. Id2 immunostaining decreased slightly, but still remained high at P90. Subcellular localization of Id2 changed from presence in cytoplasm at P14 to the nuclei at P42. Moreover, Id2 was mainly co-localized with CC-1-immunopositive mature oligodendrocytes at P42. These results may be consistent with Id2 inhibitory function in oligodendrocyte differentiation, at the end of myelination or in compaction of myelin in the Corpus callosum of postnatal rat brain.

Protective effects of catalpol on oligodendrocyte death and myelin breakdown in a rat model of chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion is thought to induce white matter lesions (WMLs) with oligodendrocyte (OLG) death and myelin breakdown. Although apoptosis is believed to be involved in the pathologic process of WMLs, effective therapies for such remain lacking. In the present study, we investigated whether catalpol, an iridoid glycoside, could act on oligodendrocytes (OLGs) and myelin sheaths in a rat chronic hypoperfusion model, and whether transcription factor cAMP-responsive element binding protein (CREB) phosphorylation is involved in the resulting neuroprotection. A rat model of chronic cerebral hypoperfusion was prepared by bilateral common carotid artery ligation. On the 30th day after hypoperfusion, OLG loss and myelin disruption in the ischemic white matter were more severe and evident than in the sham control. Spatial memory was also more seriously impaired in rats after hypoperfusion. Treatment with catalpol significantly suppressed diminished OLGs and myelin breakdown, and promoted the recovery of cognitive decline. The expression of Bcl-2 and phosphorylated CREB (p-CREB) was also significantly increased by catalpol treatment. In conclusion, catalpol could protect against hypoperfusion-induced WMLs and cognitive impairment through the p-CREB signaling pathway leading to downstream upregulation of Bcl-2. Our results suggest that catalpol may be a useful approach for treating cerebrovascular WMLs.

Analysis of Dscam diversity in regulating axon guidance in Drosophila mushroom bodies.

Dscam is an immunoglobulin (Ig) superfamily member that regulates axon guidance and targeting in Drosophila. Alternative splicing potentially generates 38,016 isoforms differing in their extracellular Ig and transmembrane domains. We demonstrate that Dscam mediates the sorting of axons in the developing mushroom body (MB). This correlates with the precise spatiotemporal pattern of Dscam protein expression. We demonstrate that MB neurons express different arrays of Dscam isoforms and that single MB neurons express multiple isoforms. Two different Dscam isoforms differing in their extracellular domains introduced as transgenes into single mutant cells partially rescued the mutant phenotype. Expression of one isoform of Dscam in a cohort of MB neurons induced dominant phenotypes, while expression of a single isoform in a single cell did not. We propose that different extracellular domains of Dscam share a common function and that differences in isoforms expressed on the surface of neighboring axons influence interactions between them.