IL-6 promotes epithelial-to-mesenchymal transition of human peritoneal mesothelial cells possibly through the JAK2/STAT3 signaling pathway.

Long-term peritoneal dialysis (PD) therapy results in functional and structural alteration of the peritoneal membrane, including epithelial-to-mesenchymal transition (EMT). Interleukin 6 (IL-6) is a local pleiotropic cytokine, hypothesized to play an important role in EMT. This study was designed to investigate the role of IL-6 in EMT and peritoneal membrane dysfunction in long-term PD patients by assessing the level of IL-6 in dialysate and exploring the relationship between IL-6, the related signaling pathway JAK2/STAT3, and EMT, using in vitro cellular and molecular techniques. Plasma and dialysate levels of IL-6 were significantly higher in PD ultrafiltration failure patients compared with patients without ultrafiltration failure and were negatively correlated with measures of PD adequacy. In vitro IL-6 treatment changed human peritoneal mesothelial cell phenotype from a typical cobblestone-like to a fibroblast-like appearance and increased cell viability. IL-6 treatment increased α-smooth muscle actin and vascular endothelial growth factor expression but decreased E-cadherin expression. IL-6 treatment activated the JAK/STAT signaling pathway. However, the JAK2/STAT3 inhibitor WP1066 prevented IL-6-induced activation of the JAK2/STAT3 pathway and EMT. We conclude that IL-6 promotes the EMT process, possibly by activating the JAK2/STAT3 signaling pathway. IL-6 may serve as a novel therapeutic target for preventing EMT, and preservation of the peritoneal membrane may arise from these studies.

Protective effect of mycophenolate mofetil on residual renal function in peritoneal dialysis patients: An open label feasibility study.

AIM: This study aims to evaluate the safety of mycophenolate mofetil (MMF) and its effect on residual renal function (RRF) during peritoneal dialysis (PD). METHODS: This is a prospective, randomized study comprising 60 PD patients. The patients were assigned either to the MMF group (MMF dosage: 1.0-1.5 g/day in two divided doses for 6 months, followed by a dose of 0.5-0.75 g/day for another 6 months) or to the control group. The patients close monitoring for 1 year. Variables related to residual renal function, including urine volume, measured glomerular filtration rate (GFR), and renal Kt/V, were measured at four time points. RESULTS: There were no significant changes in urinary protein excretion in either group (P > 0.05). The MMF group showed a significantly higher urine volume than the control group (955.38 ± 243.54 vs 786.15 ± 279.62 mL/day, P = 0.024). The renal kt/V was also significantly higher in the MMF group (0.59 ± 0.11 in MMF vs 0.50 ± 0.19 in control group, P = 0.032). There was significant difference in the renal measured GFR between the two groups at 6, 9 and 12 months (MMF vs control at 6 months, 6.14 ± 0.66 vs 5.58 ± 0.65 mL/min per 1.73m2 , P = 0.003; at 9 months, 5.68 ± 0.80 vs 4.78 ± 0.75, P < 0.001; at 12 months, 5.44 ± 0.91 vs 4.43 ± 0.93, P < 0.001). MMF was well tolerated without any serious complications. CONCLUSION: The use of MMF in PD patients tends to better preserve RRF.

Endothelin-receptor antagonist can reduce blood pressure in patients with hypertension: a meta-analysis.

The aim of this meta-analysis was to assess the effectiveness and safety of endothelin-receptor antagonist (ERA) in the patients with hypertension. Searches of the PubMed, EMBASE, and CENTRAL databases were conducted to include all the randomized control trials (RCTs). Eighteen trials including 4898 patients were used in the meta-analysis, of which nine were classified as low risk of bias and the other nine as unclear risk of bias. There was no statistically significant difference in all-cause mortality between ERA and placebo groups [6 trials, fixed effects model, RR 1.53 (0.89-2.62); random effects model, RR 1.45 (0.84-2.52)]. ERA significantly reduced 24-h ambulatory blood pressure and sitting blood pressure in patients with hypertension [5 trials, 24-h SBP: WMD -7.65 (-8.95 to -6.36), 24-h DBP: WMD -5.92 (-7.50 to -4.33); 18 trials, SBP: WMD -6.12 (-7.87 to -4.36), DBP: WMD -3.81 (-4.82 to -2.80)]. However, ERA had more adverse events [within 24 h: 3 trials, RR 1.16 (0.82-1.65); after 24 h, 13 trials, RR 1.21 (1.08-1.36)] and severe adverse events than placebo controls [SAE: 9 trials, RR 1.34 (1.13-1.60)]. In addition, there is a potential need for further RCTs that focus on the use of ERA in patients with hypertension.

Independent Association between Hyperuricemia and Histopathological Parameters in Chinese Patients with Henöch-Schönlein Purpura Nephritis.

BACKGROUND: This study aimed to investigate the role of hyperuricemia in the development of histopathological changes in HSPN. METHODS: Clinical and laboratory data pertaining to 139 adult HSPN patients with and without elevated serum uric acid levels were retrospectively evaluated. There was a 14.4% prevalence of hyperuricemia in patients with HSPN. RESULTS: Patients with hyperuricemia had higher levels of cystatin C and urine ß2-microglobulin and lower levels of HDL-C in comparison to that in patients with normal serum uric acid levels (p < 0.05). Patients with hyperuricemia had higher scores of interstitial inflammation, tubular atrophy, interstitial fibrosis, glomerulosclerosis as compared to those normouricemic patients (p < 0.05). Serum uric acid was found to be correlated independently with the presence of interstitial inflammation, tubular atrophy, interstitial fibrosis, and glomerulosclerosis by multivariate analysis (p < 0.05). CONCLUSIONS: High serum uric acid may be independently correlated with the development of tubulointerstitial lesions as well as glomerulosclerosis in HSPN.

Comparison between adults and children with Henoch-Schönlein purpura nephritis.

BACKGROUND: Henoch-Schönlein purpura (HSP) mainly affects children, but age is also thought to be an important prognostic factor. Kidney involvement is a major cause of mortality in HSP patients. The purpose of this study was to analyze the clinicopathological correlations between adults and children. METHODS: A total of 208 children and 75 adult patients with HSP nephritis (HSPN) were evaluated. All patients underwent a renal biopsy. RESULTS: Extra-renal symptoms (arthritis and abdominal pain) were more common in the pediatric patient group than in the adult group (P < 0.05), but renal symptoms (edema and hypertension) were relatively rare (P < 0.05). A significant positive correlation was noted between pathological type and clinical type (P < 0.01). Pathological activity was positively related to renal failure, abdominal pain, microscopic hematuria, hypertension, and proteinuria (P < 0.05). Pathological chronicity was positively associated with age, duration of follow-up since the onset of palpable purpura, renal failure, lower extremity edema, hypertension, and proteinuria (P < 0.05). CONCLUSIONS: Various clinicopathological differences exist between children and adults with HSPN. Massive proteinuria, renal failure, and abdominal pain usually correlated with severe pathology. Renal biopsy should be performed in both pediatric and adult HSPN patients with repeated hematuria and/or consistent minimal proteinuria.

Endothelin-receptor antagonists for diabetic nephropathy: A meta-analysis.

AIM: Endothelin-receptor antagonists may be a novel therapeutic strategy for diabetic nephropathy, but their use remains controversial. This meta-analysis seeks to evaluate the effectiveness and safety of endothelin-receptor antagonists for patients with diabetic nephropathy. METHODS: Literature reviews of the PubMed, EMBASE and CENTRAL databases were conducted to identify randomized controlled trials (RCTs) comparing endothelin-receptor antagonist treatment with placebo in patients with diabetic nephropathy. Quality assessment was performed by using the Cochrane Handbook's tools for assessing risk of bias; meta-analysis was conducted by RevMan 5.3. RESUTLS: Five RCTs (n=2034 patients) were included for analysis. Compared with placebo, endothelin-receptor antagonists showed significant benefits for lowering albuminuria (five trials, n=2034 patients; SMD 0.66 95% confidence interval (CI) 0.56 to 0.76), but there was no significant difference in the risk of death (two trials, n=1674 patients; RR 1.49 95% CI 0.81 to 2.76). In addition, risk of cardiovascular events and other serious adverse events were significantly higher in the endothelin-receptor antagonists group than the placebo group (four trials, n=1956 patients; RR 1.45 95% CI 1.07 to 1.97; five trials, n=2034 patients; RR 1.32 95% CI 1.10 to 1.58). CONCLUSION: Endothelin-receptor antagonists can reduce albuminuria in patients with diabetic nephropathy, although use resulted in more serious adverse events compared with placebo. There is a potential need for further RCTs, which has larger sample size and longer duration.

The application of two drainage angles in neurocritical care patients with complicated pneumonia: a randomized controlled trial.

Background: Although head elevation is an early first-line treatment for elevated intracranial pressure (ICP), the use of the head-down or prone position in managing neurocritical patients is controversial because a change in a position directly affects the intracranial and cerebral perfusion pressure, which may cause secondary brain injury and affect patient outcomes. This study compared the effects of two postural drainage positions (30° head-up tilt and 0° head flat) on the prognosis of neurocritical care patients with complicated pneumonia and a clinical pulmonary infection score (CPIS) ≥5 points to provide a reference for selecting appropriate postural drainage positions for patients with pneumonia in neurocritical care units. Methods: A prospective randomized controlled study was conducted with 62 neurocritical care patients with complicated pneumonia. The patients were categorized into control (=31) and experimental (=31) groups in a 1:1 ratio using a simple randomized non-homologous pairing method. Emphasis was placed on matching the baseline characteristics of the two groups, including patient age, sex, height, weight, Glasgow Coma Scale score, heart rate, mean arterial pressure, cough reflex, and mechanical ventilation usage to ensure comparability. Both groups received bundled care for artificial airway management. The control group maintained a standard postural drainage position of 0° head-flat, whereas the experimental group maintained a 30° head-up tilt. The efficacy of the nursing intervention was evaluated by comparing the CPIS and other therapeutic indicators between the two groups after postural drainage. Results: After the intervention, the within-group comparison showed a significant decrease in the CPIS (P < 0.001); procalcitonin levels showed a significant decreasing trend (P < 0.05); the arterial oxygen pressure significantly increased (P < 0.05); the oxygenation index significantly increased (P < 0.001); and the aspiration risk score showed a significant decreasing trend (P < 0.001). A between-group comparison showed no significant differences in any of the indicators before and after the intervention (P < 0.05). Conclusion: Postural drainage positions of 30° head-up tilt and 0° head-flat can improve the CPIS and oxygenation in patients without adverse effects. Therefore, we recommend that patients under neurological intensive care and having pneumonia be drained in a 30° head-up tilt position with good centralized care of the lung infection. Trial registration: The study, "Study of Angles of Postural Drainage in Neurocritical Patients with Pneumonia," was registered in the Protocol Registration Data Element Definitions for Interventional Study database (# ChiCTR2100042155); date of registration: 2021-01-14.

Edaravone for acute ischaemic stroke.

BACKGROUND: Neuroprotection is a promising therapeutic strategy for the treatment of acute ischaemic stroke. Edaravone is a neuroprotective agent that has been widely used in China, and several studies have suggested that it may be beneficial in acute ischaemic stroke. OBJECTIVES: To assess the efficacy and safety of edaravone for acute ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (November 2010) and the Chinese Stroke Trials Register (November 2010). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE (1950 to November 2010), EMBASE (1980 to November 2010), China National Knowledge Infrastructure (1979 to November 2010), Chinese Biomedical Database (1979 to November 2010), Chinese Evidence-Based Medicine Database (November 2010) and Chinese Science and Technology Journals Database (1980 to November 2010). In an attempt to identify further published, unpublished and ongoing trials we searched reference lists and clinical trials and research registers, and contacted a pharmaceutical company, researchers and study authors. SELECTION CRITERIA: We included randomised controlled trials comparing edaravone with placebo or no intervention in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors selected trials for inclusion, assessed trial quality and independently extracted the data. MAIN RESULTS: We included three trials, involving 496 participants, and defined four trials as waiting assessment. All three included trials were of edaravone plus another treatment compared with the other treatment alone. The dose of edaravone injections in the three trials was the same at 60 mg per day. The course of treatment in all three trials is 14 days. None of the included trials reported the pre-specified primary outcome of death or dependency defined using the modified Rankin scale during the follow-up period. The three trials evaluated the effect of edaravone at different times and using different methods. All three trials reported adverse events; there were no differences between the treatment group and the control group. Overall, edaravone appeared to increase the proportion of participants with marked neurological improvement compared with the control group, and the difference was significant (risk ratio (RR) 1.99, 95% confidence interval (CI) 1.60 to 2.49). AUTHORS' CONCLUSIONS: The risk of bias in the included trials was moderate and the sample was small. Hence, although the data in this review show an effective treatment trend of edaravone for acute ischaemic stroke, further large, high-quality trials are required to confirm this trend.

[The correlation between uric acid and the incidence and prognosis of kidney diseases: a systematic review and meta-analysis of cohort studies].

OBJECTIVE: To evaluate the association of serum uric acid and the incidence and prognosis of kidney diseases systematically, so as to provide reference for the treatment and prevention of kidney diseases. METHODS: Literatures related to the associations between serum uric acid and incidence and prognosis of kidney diseases were selected from the Chinese Biomedical Literature Database (CBM) (January 1982 to March 2010), EMBASE (January 1966 to March 2010) and Medline (January 1950 to March 2010) for cohort studies. Two researchers independently screened the studies, assessed the risk of bias of included studies using the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies and extracted data. Stata 10.0 was used to calculate the pooled relative risk. RESULTS: Twenty-one eligible cohort studies were selected, of which 11 on incidence of kidney diseases (n = 276 801), and 10 on the prognosis of kidney diseases (n = 3004). Meta analysis was performed based on data influencing incidence and prognosis factors of kidney diseases except for serum uric acid. The results showed, (1) uric acid and incidence of kidney diseases: hyperuricemia could increase the risk of kidney diseases (RR = 1.49, 95%CI 1.27 - 1.75); (2) uric acid and prognosis of patients with kidney diseases:hyperuricemia could deteriorate the kidney function (RR = 1.35, 95%CI 1.12 - 1.63) and increase the risk of mortality (RR = 1.67, 95%CI 1.29 - 2.16). CONCLUSION: Uric acid is an independent risk factor for incidence of kidney diseases and poor prognosis of patients with kidney diseases. Further high quality clinical trials with long-term follow up should be conducted to determine whether lowering uric acid levels would be of clinical benefit in the prevention and treatment of kidney diseases, so as to provide direct evidence for clarifying correlation between uric acid and kidney diseases and the prevention and treatment for patients with high uric acid.

Effects of hyperuricemia on renal function of renal transplant recipients: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Hyperuricemia is an independent risk factor of nephropathy, but its role in renal transplant recipients (RTRs) is controversial. METHODS: Based on the methods of Cochrane systematic reviews, we searched MEDLINE (1948-2011.6), EMBASE (1956-2011.6), CBM (Chinese Biomedicine Database) (1978-2011.6) to identify cohort studies assessing the association between uric acid level and kidney allograft. Two authors independently screened the studies, assessed the risk of bias of included studies and extracted data. Unadjusted odds ratio (OR), mean difference (MD), adjusted hazard ratio (aHR) and their corresponding 95%CI were pooled to assess the effects of hyperuricemia on kidney allograft. RESULTS: Twelve cohort studies were included and the quality was moderate to high based on the NEWCASTLE-OTTAWA quality assessment scale. RTRs with hyperuricemia had lower eGFR (P<0.0001, 95%CI-16.34∼6.14) and higher SCr (P<0.00001, 95%CI 0.17∼0.31) than those with normal uric acid level. Meta-analysis showed that hyperuricemia was a risk factor of chronic allograft nephropathy (Unadjusted OR = 2.85, 95%CI 1.84∼4.38, adjusted HR = 1.65, 95%CI 1.02∼2.65) and graft loss (Unadjusted OR = 2.29, 95%CI 1.55∼3.39; adjusted HR = 2.01, 95%CI 1.39∼2.94). CONCLUSIONS: Current evidence suggests that hyperuricemia may be an independent risk factor of allograft dysfunction. Hyperuricemia may modestly increase the risk of poor outcomes of RTRs. Future research is needed to verify whether lowering uric acid level could improve the kidney function and prognosis of RTRs with hyperuricemia.

Quality of reporting of trial abstracts needs to be improved: using the CONSORT for abstracts to assess the four leading Chinese medical journals of traditional Chinese medicine.

BACKGROUND: Due to language limitations, the abstract of journal article may be the only way for people of non-Chinese speaking countries to know about trials in traditional Chinese medicine (TCM). However, little is known about the reporting quality of these trial abstracts. Our study is to assess the reporting quality of abstracts of randomized controlled trials (RCT) published in four leading Chinese medical journals of TCM, and to identify any differences in reporting between the Chinese and English version of the same abstract publication. METHOD: Two reviewers hand-searched the Chinese Journal of Integrated Traditional and Western Medicine, the Chinese Journal of Integrative Medicine, the China Journal of Chinese Materia Medica and the Chinese Acupuncture & Moxibustion for all abstracts of RCTs published between 2006 and 2007. Two reviewers independently assessed the reporting quality of the Chinese and English version of all eligible abstracts based on a modified version of the CONSORT for reporting randomised trials in journal and conference abstracts (CONSORT for abstracts). RESULTS: We identified a total of 345 RCTs of TCM with both a Chinese and English abstract. More than half of Chinese abstracts reported details of the trial participants (68%; 234/345), control group intervention (52%; 179/345), the number of participants randomized (73%; 253/345) and benefits when interpreting the trial results (55%; 190/345). Reporting of methodological quality or key features of trial design and trial results were poor; only 2% (7/345) included details of the trial design, 3% (11/345) defined the primary outcome, 5% (17/345) described the methods of random sequence generation, and only 4% (13/345) reported the number of participants analyzed. No abstracts provided details on allocation concealment and trial registration. The percentage agreement in reporting (between the Chinese and English version of the same abstract) ranged from 84% to 100% across individual checklist item. CONCLUSION: The reporting quality of abstracts of RCTs published in these four TCM journals needs to be improved. Since none of the four journals adopted CONSORT for Abstracts, we hope that the introduction and adoption of CONSORT for Abstracts by TCM journals will lead to an improvement in reporting quality.

[Effect and safety of the therapies for acute myocardial infarction patients with failed thrombolytic therapy: a systematic review].

OBJECTIVE: To assess the effect and safety of therapies in common use for acute myocardial infarction (AMI) patients with failed thrombolytic therapy. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2006), MEDLINE (1966 to July 2006), EMBASE (1984 to July 2006), China National Knowledge Infrastructure (CNKI, 1994 to July 2006), China Biomedicine Database disc (CBMdisc, 1980 to July 2006). We also searched several key Chinese journals in the field of cardiovascular diseases. The language was limited to Chinese and English. We included all the randomized controlled trials (RCTs) for acute myocardial infarction patients with failed thrombolytic therapy. Two authors independently assessed the methodological quality of the included studies, the data were analyzed by RevMan 4.2.8 from the Cochrane Collaboration. RESULTS: Nine RCTs met the inclusion criteria. A significant difference was found between the rescue percutaneous coronary intervention (PCI) group and conventional treatment group in the mortality rate at the end of the follow-up [RR=0.64, 95%CI (0.41, 0.98)]. Thromboembolic stroke and bleeding in rescue PCI group were significantly higher than that in conventional treatment group [RR=4.39, 95%CI (1.14, 16.87), and RR=2.79, 95%CI (1.55, 5.02), respectively]. Compared with conventional therapy, rescue thrombolytic treatment was associated with a significantly higher reperfusion rate [RR=2.92, 95%CI (1.75, 4.85)]. Comparison between rescue PCI with rescue thrombolytic treatment revealed that the revascularization rate in rescue PCI group was significantly lower than that in rescue thrombolytic group [RR=0.57, 95%CI (0.34, 0.95)], and the incidence of bleeding was significantly higher in rescue PCI group [RR=2.15, 95%CI (1.27, 3.63)]. Comparison of glycoprotein (GP)IIb/IIIa receptor antagonists with standard treatment showed no significant difference between them in the mortality rate and bleeding rate at the end of the follow-up. CONCLUSION: Current evidence does not confirm the effect or safety of the therapies for AMI patients with failed thrombolytic therapy, nor support the routine use of these therapies in clinical practice except for rescue PCI that reduces mortality compared with traditional treatment. Further high-quality randomized controlled trials are needed to provide reliable evidence for the treatments of AMI patients with failed thrombolytic therapy.