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1.  Bifidobacterium infantis attenuates colitis by regulating T cell subset responses 
World Journal of Gastroenterology : WJG  2014;20(48):18316-18329.
AIM: to investigate the effect of Bifidobacterium infantis (B. infantis) on the T cell subsets and in attenuating the severity of experimental colitis in mice.
METHODS: Normal BALB/c mice were fed different doses of B. infantis for 3 wk, and T cell subsets and related cytokine profiles in mesenteric lymph nodes (MLNs) were detected by flow cytometry and real-time RT-PCR. Colitis was induced by administration of trinitrobenzene sulfonic acid (TNBS) in mice. Before colitis induction, mice were fed high dose B. infantis for 3 wk. Cytokine profiles in MLNs and histological changes of colonic tissue were examined 6 d after colitis induction.
RESULTS: No significant change in cytokine profiles was observed in normal mice fed low dose B. infantis. However, Th1-related cytokines (IL-2, IFN-γ, IL-12p40), Th17-related transcription factor and cytokines (RORγt, IL-21, IL-23), regulatory T cell (Treg)-related transcription factor and cytokines (Foxp3, IL-10) were increased in normal mice fed high dose B. infantis. Furthermore, flow cytometry assay showed B. infantis increased the numbers of CD4+Foxp3+ Tregs and Th17 cells in MLNs. Colitis was successfully induced by TNBS in mice, characterized by colonic inflammation and aberrant Th1 and Th17 responses. Feeding high dose B. infantis for 3 wk before colitis induction decreased the inflammatory cell infiltration and goblet cell depletion and restored the intestinal epithelium. In addition, B. infantis feeding reduced Th1-related cytokines (T-bet, IL-2 and IFN-γ) and Th17-related cytokines (IL-12p40, RORγt, IL-17A, IL-21 and IL-23), and increased Treg-related molecules (Foxp3, IL-10 and TGF-β) in colitis mice.
CONCLUSION: B. infantis effectively attenuates TNBS-induced colitis by decreasing Th1 and Th17 responses and increasing Foxp3+ Treg response in the colonic mucosa.
PMCID: PMC4277968  PMID: 25561798
Bifidobacterium; Colitis; Cytokines; Th17; Regulatory T cells
2.  Evaluation of the CKD-EPI Equation in Multiple Races and Ethnicities 
Kidney international  2010;79(5):555-562.
The CKD-EPI equation reduces bias and improves accuracy for GFR estimation compared to the MDRD Study equation. Creatinine generation differs among racial-ethnic groups but both equations only consider Blacks vs other. We developed and validated a GFR-estimating equation that includes a 4-level race variable.
Equations were developed in pooled data from 10 studies (N=8254) and validated in 17 additional studies from the US and Europe [CKD-EPI validation database (N=4014)], and in studies from China (N=675), Japan (N=248) and South Africa (N=99). Race was defined as a 2-level variable (Black vs other) and a 4-level variable (Black, Asian, Native American and Hispanic vs other).
Coefficients for Black, Asian and Native American and Hispanic resulted in 15%, 5% and 1% higherlevels of estimated GFR, respectively, compared to others. The 2-level race equation had minimal bias in Blacks, Native Americans, Hispanics and others [−0.8 (−2.0,0.6), 2.3 (−2.1,5.1), and 2.8 (2.4,3.2) ml/min/1.73 m2, respectively) in the CKD-EPI validation database. The 4-level race equation improved bias in CKD-EPI Asians (0.8 (−2.2,2.6) vs 2.1 (0.3,4.4) ml/min/1.73 m2) and in Chinese (1.3 (0.6,2.2) vs 2.7 (1.9,3.7) ml/min/1.73 m2). Both equations had a large bias in Japanese [−17.8 (−0.1,−14.7) and −21.4 (−23.2,−18.2) ml/min/1.73 m2)] and South Africans [−12.4 (−18.3,−7.6) and −12.5 (−18.3,−7.6) ml/min/1.73 m2.
A multilevel variable for race developed in one geographic region may not be applicable in other regions. The 2-level race variable in the CKD-EPI equation can be used for all racial-ethnic groups in the US and Europe.
PMCID: PMC4220293  PMID: 21107446
3.  Novel mechanisms of tube-size regulation revealed by the Drosophila trachea 
Cell and tissue research  2013;354(2):10.1007/s00441-013-1673-z.
The size of various tubes within tubular organs such as the lung, vascular system and kidney must be finely tuned for the optimal delivery of gases, nutrients, waste and cells within the entire organism. Aberrant tube sizes lead to devastating human illnesses, such as polycystic kidney disease, fibrocystic breast disease, pancreatic cystic neoplasm and thyroid nodules. However, the underlying mechanisms that are responsible for tube-size regulation have yet to be fully understood. Therefore, no effective treatments are available for disorders caused by tube-size defects. Recently, the Drosophila tracheal system has emerged as an excellent in vivo model to explore the fundamental mechanisms of tube-size regulation. Here, we discuss the role of the apical luminal matrix, cell polarity and signaling pathways in regulating tube size in Drosophila trachea. Previous studies of the Drosophila tracheal system have provided general insights into epithelial tube morphogenesis. Mechanisms that regulate tube size in Drosophila trachea could be well conserved in mammalian tubular organs. This knowledge should greatly aid our understanding of tubular organogenesis in vertebrates and potentially lead to new avenues for the treatment of human disease caused by tube-size defects.
PMCID: PMC3812325  PMID: 23824100
Trachea; Tube size; Luminal matrix; Apical secretion; Cell polarity; Endocytosis; Drosophila
4.  PO2 Cycling Reduces Diaphragm Fatigue by Attenuating ROS Formation 
PLoS ONE  2014;9(10):e109884.
Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ∼30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses.
PMCID: PMC4192541  PMID: 25299212
5.  Current status of maintenance hemodialysis in Beijing, China 
Kidney International Supplements  2013;3(2):167-169.
The Beijing Hemodialysis Quality Control and Improvement Center started patient data collection from 2007. We report here the trends in incidence, prevalence, and mortality of end-stage renal disease (ESRD) patients on maintenance hemodialysis (MHD). The incidence increased from 94 per million population in 2007 to 147.3 per million population in 2010. The leading cause of ESRD changed from chronic glomerulonephritis (32.1%) to diabetes (40.1%). The point prevalence of MHD at the end of 2006 was 269 per million population, and gradually increased to 509 per million population in the end of 2010. The leading cause of ESRD in 2010 prevalent patients was chronic nephritis (33.9%), followed by diabetes (29.5%). The annual mortality varied from 7.4 to 9.0%. Old or diabetic patients suffered a higher mortality. The 2010 prevalent MHD patients achieved KDOQI hemoglobin, calcium, phosphate, and intact parathyroid hormone guidelines, which was comparable to other DOPPS (Dialysis Outcome and Practice Pattern Study) countries; Beijing MHD patients had a relatively higher albumin level.
PMCID: PMC4089754  PMID: 25018982
epidemiology; hemodialysis; incidence; mortality; prevalence
6.  Association of a common genetic variant in prostate stem cell antigen with cancer risk 
Archives of Medical Science : AMS  2014;10(3):425-433.
Polymorphisms in the prostate stem cell antigen (PSCA) gene have been hypothesized to increase the genetic susceptibility to cancers. The common sequence variation in PSCA rs2294008 (C>T) has been implicated in cancer risk. However, results of the relevant published studies were somewhat underpowered and controversial in general.
Material and methods
To evaluate the role of PSCA rs2294008 (C>T) genotype in global cancer, we performed a pooled analysis of all the available published studies involving 22,817 cancer patients and 27,753 control subjects.
The results showed evidence that PSCA rs2294008 (C>T) was associated with increased total cancer risk in the overall comparisons. Stratified analysis by cancer type indicated that PSCA rs2294008 T is associated with increased risk of gastric cancer (OR = 1.24, 95% CI = 1.09–1.42, pheterogeneity < 0.001, I2 = 88.0%) and bladder cancer (OR = 1.07, 95% CI = 1.04–1.11, pheterogeneity = 0.108, I2 = 55.0%) by allelic contrast. Furthermore, in stratified analysis by histological types of gastric cancer, this PSCA variant showed significant associations with diffuse type (OR = 1.81, 95% CI = 1.16–2.81, pheterogeneity < 0.001, I2 = 88.9%) but not intestinal type (OR = 1.29, 95% CI = 0.95–1.74, pheterogeneity < 0.001, I2 = 85.2%) in a dominant genetic model. Similar results were found in Asian and European descendents and population-based studies.
In all, our meta-analysis suggests that PSCA rs2294008 (C>T) may play allele-specific roles in cancer development. Further prospective studies with larger numbers of participants worldwide should be performed in different kinds of cancer and other descendents in more detail.
PMCID: PMC4107248  PMID: 25097570
prostate stem cell antigen; polymorphism; cancer risk; meta-analysis
7.  Effectiveness of accommodation and constant resistance training on maximal strength and power in trained athletes 
PeerJ  2014;2:e441.
Accommodation resistance is a training technique that may improve strength and power gains beyond those achieved by traditional free weights. In this method, chains are either added on a free-weight bar and combined with traditional plates or added to the bar as the entire load.
Purpose. The aim of the current study was to compare the effectiveness of accommodation and constant resistance training methods during a four-week period on maximal strength and power in trained athletes.
Methods. This study was comprised of 24 trained athletes, including 16 trained males [8 Wushu athletes (Kung-Fu) and 8 wrestlers, age: 20.5 ± 2.00 yrs. old]. Participants were initially tested on weight, body circumference, fat percent, upper and lower body maximal strength, determined by the 1-repetition maximum (1RM) test, which determines the greatest amount of weight a person can successfully lift, and upper and lower body power. Participants were equally randomized to either accommodation or constant resistance training groups. Both groups underwent resistance training for a four-week period that consisted of three sessions per week. Multivariate repeated-measures analyses of variance of the data were used to verify significant differences in strength and power between groups. The modified Bonferroni post hoc test was used to compare the obtained results in pre-, mid-, and post test.
Results. In the accommodation resistance group, there was a significant difference in lower body maximal strength compared to the constant group (163.12 ± 18.82 kg in the accommodation group vs. 142.25 ± 20.04 kg in the constant group, P = 0.04). No significant differences were found in upper body power, lower body power, and upper body maximal strength between the two groups (P > 0.05).
Conclusion. Although there was only a significant difference in lower body maximal strength between groups, accommodation resistance training may induce a physiological training response by improving the strength and power of stabilizing muscle groups required to balance the bar if consistently used over time.
PMCID: PMC4081144  PMID: 25024910
Muscle power; 1-Repetition maximum (1RM); Accommodation training; Constant training
8.  The role of exercise training on lipoprotein profiles in adolescent males 
Major cardiovascular disorders are being recognized earlier in life. In this study we examined the effects of swimming and soccer training on male adolescent lipid-lipoprotein profiles relative to a maturity matched control group to determine the effects of these exercises on specific cardiovascular risk and anti-risk factors.
Forty five adolescent males (11.81 ± 1.38 yr) including swimmers (SW), soccer players (SO), and non-athlete, physically active individuals as controls (C), participated in this study. Training groups completed 12-wk exercise programs on three non-consecutive days per week. Plasma low-density lipoprotein (LDL), very low density lipoprotein (VLDL), high density lipoprotein (HDL), apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), total cholesterol (TC), and triglyceride (TG) levels were measured in control, pre-training, during-training, and post-training.
In response to the 12-wk training period, the SO group demonstrated a decrease in the mean LDL level compared to the SW and C (SW: 0.15%; SO: −9.51%; C: 19.59%; p < 0.001) groups. There was an increase in both the SW and SO groups vs. the control in mean HDL (SW: 5.66%; SO: 3.07%; C: −7.21%; p < 0.05) and apoA-I (SW: 3.86%; SO: 5.48%; C: −1.01%; p < 0.05). ApoB was considerably lower in the training groups vs. control (SW: −9.52%; SO: −13.87%; C: 21.09%; p < 0.05). ApoA-I/apoB ratio was significantly higher in training groups vs. control (SW: 16.74%; SO: 23.71%; C: −17.35%; p < 0.001). There were no significant differences between groups for other factors.
The favorable alterations in LDL, HDL, apoA-I, and apoB observed in the training groups suggest that both regular swimming or soccer exercise can potentially mitigate cardiovascular risk in adolescent males.
PMCID: PMC4064523  PMID: 24912476
Cardiovascular risk; Anti-risk factors; Cholesterol; Lipids
9.  Potential biomarkers relating pathological proteins, neuroinflammatory factors and free radicals in PD patients with cognitive impairment: a cross-sectional study 
BMC Neurology  2014;14:113.
Cognitive impairment strikingly reduces the quality of life of Parkinson’s disease (PD) patients. Studies find that pathological proteins, neuroinflammatory factors and free radicals may involve in the pathogenesis of cognitive impairment of PD, however, results are inconclusive.
We recruited 62 PD patients and 31 healthy controls. PD patients were identified with cognitive impairment, including PD with mild cognitive impairment (PD-MCI) and PD with dementia (PDD) according to the diagnostic criteria for PD-MCI and PDD issued by Movement Disorder Society Task Force. The levels of pathological proteins, including β-amyloid 1–42 (Aβ1-42),Total-tau (T-tau) and phosphorelated tau (P-tau), neuroinflammatory factors,including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interferon-γ (INF-γ) and prostaglandin E2 (PGE2), free radicals, including hydroxyl radical (·OH), hydrogen peroxide (H2O2) and nitric oxide (NO) in cerebrospinal fluid(CSF) were detected. The levels of above factors in CSF were compared among healthy controls and patients with and without cognitive impairment. Correlation analyses were performed between Montreal Cognitive Assessment (MoCA) score and the levels of above factors in CSF.
T-tau level in CSF from PD-CI patients are significantly elevated comparing with those without cognitive impairment and controls (P = 0.016 and 0.004, respectively). The levels of P-tau (S396) and · OH in PD-CI patients are significantly higher than controls (P = 0.001 and 0.014, respectively). IL-6 levels in PD-CI patients are strikingly enhanced comparing with those without cognitive impairment (P = 0.005). MoCA score is negatively correlated with the levels of T-tau (r = -0.340), P-tau (S396) (r = -0.448), IL-6 (r = -0.489) and · OH (r = -0.504) in PD-CI patients.
Elevated levels of T-tau, P-tau (S396), IL-6 and · OH in CSF are significantly correlated with cognitive impairment in PD patients. This investigation may suggest the potential biomarkers relating pathological proteins, neuroinflammatory factors and free radicals in PD patients with cognitive impairment.
PMCID: PMC4035732  PMID: 24884485
Parkinson’s disease; Cognitive impairment; Pathological proteins; Neuroinflammatory factors; Free radicals; Cerebrospinal fluid
10.  Mathematical modeling on vacuum drying of Zizyphus jujuba Miller slices 
The thin-layer vacuum drying behavior of Zizyphus jujuba Miller slices was experimentally investigated at the temperature of 50, 60, and 70 °C and the mathematical models were used to fit the thin-layer vacuum drying of Z. jujuba slices. The increase in drying air temperature resulted in a decrease in drying time. The drying rate was found to increase with temperature, thereby reducing the total drying time. It was found that Z. jujuba slices with thickness of 4 mm would be dried up to 0.08 kg water/kg dry matter in the range of 180–600 min in the vacuum dryer at the studied temperature range from 70 to 50 °C. The Midilli et al. model was selected as the most appropriate model to describe the thin-layer drying of Z. jujuba slices. The diffusivity coefficient increased linearly over the temperature range from 1.47 × 10−10 to 3.27 × 10−10 m2/s, as obtained using Fick’s second law. The temperature dependence of the effective diffusivity coefficient followed an Arrhenius-type relationship. The activation energy for the moisture diffusion was determined to be 36.76 kJ/mol.
PMCID: PMC3550957  PMID: 24425895
Drying kinetics; Vacuum drying; Zizyphus jujuba Miller slices; Modeling; Effective diffusivity; Activation energy
11.  Sleep Disorders in Parkinson’s Disease: Clinical Features, Iron Metabolism and Related Mechanism 
PLoS ONE  2013;8(12):e82924.
To investigate clinical features, iron metabolism and neuroinflammation in Parkinson’s disease (PD) patients with sleep disorders (SD).
211 PD patients were evaluated by Pittsburgh Sleep Quality Index (PSQI) and a body of scales for motor symptoms and non-motor symptoms. 94 blood and 38 cerebral spinal fluid (CSF) samples were collected and iron and its metabolism-relating proteins, neuroinflammatory factors were detected and analyzed.
136 cases (64.5%) of PD patients were accompanied by SD. Factor with the highest score in PSQI was daytime dysfunction. Depression, restless leg syndrome, autonomic symptoms and fatigue contributed 68.6% of the variance of PSQI score. Transferrin level in serum and tumor necrosis factor–α level in CSF decreased, and the levels of iron, transferrin, lactoferrin and prostaglandin E2 in CSF increased in PD patients with SD compared with those without SD. In CSF, prostaglandin E2 level was positively correlated with the levels of transferrin and lactoferrin, and tumor necrosis factor–α level was negatively correlated with the levels of iron, transferrin and lactoferrin in CSF.
Depression, restless leg syndrome, autonomic disorders and fatigue are the important contributors for the poor sleep in PD patients. Abnormal iron metabolism may cause excessive iron deposition in brain and be related to SD in PD patients through dual potential mechanisms, including neuroinflammation by activating microglia and neurotoxicity by targeting neurons. Hence, inhibition of iron deposition-related neuroinflammation and neurotoxicity may cast a new light for drug development for SD in PD patients.
PMCID: PMC3871565  PMID: 24376607
12.  Tonotopic reorganization and spontaneous firing in inferior colliculus during both short and long recovery periods after noise overexposure 
Noise induced injury of the cochlea causes shifts in activation thresholds and changes of frequency response in the inferior colliculus (IC). Noise overexposure also induces pathological changes in the cochlea, and is highly correlated to hearing loss. However, the underlying mechanism has not been fully elucidated. In this study, we hypothesized that overexposure to noise induces substantial electrophysiological changes in the IC of guinea pigs.
During the noise exposure experiment, the animals were undergoing a bilateral exposure to noise. Additionally, various techniques were employed including confocal microscopy for the detection of cochlea hair cells and single neuron recording for spontaneous firing activity measurement. There were alterations among three types of frequency response area (FRA) from sound pressure levels, including V-, M-, and N-types. Our results indicate that overexposure to noise generates different patterns in the FRAs. Following a short recovery (one day after the noise treatment), the percentage of V-type FRAs considerably decreased, whereas the percentage of M-types increased. This was often caused by a notch in the frequency response that occurred at 4 kHz (noise frequency). Following a long recovery from noise exposure (11–21 days), the percentage of V-types resumed to a normal level, but the portion of M-types remained high. Interestingly, the spontaneous firing in the IC was enhanced in both short and long recovery groups.
Our data suggest that noise overexposure changes the pattern of the FRAs and stimulates spontaneous firing in the IC in a unique way, which may likely relate to the mechanism of tinnitus.
PMCID: PMC3878917  PMID: 24320109
Cochlea; Noise; Tinnitus; Hair cells; Inferior colliculus
13.  Cross-over study of influence of oral vitamin C supplementation on inflammatory status in maintenance hemodialysis patients 
BMC Nephrology  2013;14:252.
Both vitamin C deficiency and inflammation are prevalent in maintenance hemodialysis (MHD) patients. In this study, we aimed to elucidate the effect of oral vitamin C supplementation on inflammatory status in MHD patients with low vitamin C level and high hypersensitive C-reactive protein (hs-CRP) level.
A total of 128 patients were recruited in our present study. Patients were divided into two groups. In group 1 (n = 67), patients were orally administered with 200 mg/day vitamin C in the first 3 months, and then the vitamin C supplementation was withdrawn in the next 3 months. In group 2 (n = 61), patients were not given vitamin C in the first 3 months, and then they were orally administered with 200 mg/day in the next 3 months. Levels of hs-CRP, prealbumin, albumin and hemoglobin as well as the EPO resistance index (ERI) were determined at the baseline and every 3 months throughout the study. Plasma vitamin C level was determined by high-performance liquid chromatography with UV detection.
Among the 128 patients, 28 of them dropped out of the study before completion. Consequently, a total of 100 patients (group 1: n = 48; group 2: n = 52) were included in the final analysis. At the baseline, the plasma vitamin C level of all patients was less than 4 μg/mL. However, this proportion was decreased to 20% after the vitamin C supplementation for 3 months. Compared with patients without the vitamin C supplementation, a decreased level of hs-CRP and an increased level of prealbumin were induced by the vitamin C supplementation for 3 months in both groups. However, levels of these biomarkers returned to their original state after the supplementation was withdrawn. Same beneficial effects on plasma albumin, hemoglobin and ERI response to vitamin C supplementation were observed in the two groups without statistical significance.
The inflammatory status in MHD patients with plasma vitamin C deficiency and high levels of inflammatory markers could be partially improved by long-term oral administration of small doses of vitamin C.
Trial registration
The clinical trial number: NCT01356433.
PMCID: PMC3840610  PMID: 24228847
Hemodialysis; Inflammation; Vitamin C
14.  IL-13 induces esophageal remodeling and gene expression by an eosinophil-independent IL-13Rα2-inhibited pathway 
Eosinophilic esophagitis (EE) is an emerging disease associated with both food and respiratory allergy characterized by extensive esophageal tissue remodeling and abnormal esophageal gene expression including increased IL-13. We investigated the ability of increased airway IL-13 to induce EE-like changes. Mice that overexpress an IL-13 transgene in the lung (but not esophagus) accumulated esophageal IL-13 and developed prominent esophageal remodeling with epithelial hyperplasia, angiogenesis, collagen deposition and increased circumference. IL-13-induced marked changes in esophageal transcripts overlapped with the human EE esophageal transcriptome. IL-13-induced esophageal eosinophilia was eotaxin-1 (but not eotaxin-2) dependent but remodeling occurred independent of eosinophils, as demonstrated by studying eosinophil lineage-deficient IL-13 transgenic mice. IL-13-induced remodeling was significantly enhanced by IL-13Rα2 gene deletion, indicating an inhibitory effect of IL-13Rα2. In the murine system, there was partial overlap between IL-13-induced genes in the lung and esophagus, yet the transcriptomes were also divergent at the tissue level. In human esophagus, IL-13 levels correlated with the magnitude of the EE transcriptome. In conclusion, inducible airway expression of IL-13 results in an esophageal gene expression and extensive tissue remodeling pattern that resembles human EE. Notably, we have identified a pathway for inducing EE-like changes that is IL-13-driven, eosinophil-independent and suppressed by IL-13Rα2.
PMCID: PMC3746758  PMID: 20543112
15.  Association between family members of dialysis patients and chronic kidney disease: a multicenter study in China 
BMC Nephrology  2013;14:19.
Family members of patients with end stage renal disease were reported to have an increased prevalence of chronic kidney disease (CKD). However, studies differentiated genetic and non-genetic family members are limited. We sought to investigate the prevalence of CKD among fist-degree relatives and spouses of dialysis patients in China.
Seventeen dialysis facilities from 4 cities of China including 1062 first-degree relatives and 450 spouses of dialysis patients were enrolled. Sex- and age- matched controls were randomly selected from a representative sample of general population in Beijing. CKD was defined as decreased estimated glomerular (eGFR < 60 mL/min/1.73 m2) or albuminuria.
The prevalence of eGFR less than 60 mL/min/1.73 m2, albuminuria and the overall prevalence of CKD in dialysis spouses were compared with their counterpart controls, which was 3.8% vs. 7.8% (P < 0.01), 16.8% vs. 14.6% (P = 0.29) and 18.4% vs. 19.8% (P = 0.61), respectively. The prevalence of eGFR less than 60 mL/min/1.73 m2, albuminuria and the overall prevalence of CKD in dialysis relatives were also compared with their counterpart controls, which was 1.5% vs. 2.4% (P = 0.12), 14.4% vs. 8.4% (P < 0.01) and 14.6% vs. 10.5% (P < 0.01), respectively. Multivariable Logistic regression analysis indicated that being spouses of dialysis patients is negatively associated with presence of low eGFR, and being relatives of dialysis patients is positively associated with presence of albuminuria.
The association between being family members of dialysis patients and presence of CKD is different between first-degree relatives and spouses. The underlying mechanisms deserve further investigation.
PMCID: PMC3565899  PMID: 23331610
Chronic kidney disease; Albuminuria; Renal function; Relatives; Spouses; Screening
16.  Protective Effect of Anthocyanins from Lingonberry on Radiation-induced Damages  
There is a growing concern about the serious harm of radioactive materials, which are widely used in energy production, scientific research, medicine, industry and other areas. In recent years, owing to the great side effects of anti-radiation drugs, research on the radiation protectants has gradually expanded from the previous chemicals to the use of natural anti-radiation drugs and functional foods. Some reports have confirmed that anthocyanins are good antioxidants, which can effectively eliminate free radicals, but studies on the immunoregulatory and anti-radiation effects of anthocyanins from lingonberry (ALB) are less reported. In this experiment, mice were given orally once daily for 14 consecutive days before exposure to 6 Gy of gamma-radiation and were sacrificed on the 7th day post-irradiation. The results showed that the selected dose of extract did not lead to acute toxicity in mice; while groups given anthocyanins orally were significantly better than radiation control group according to blood analysis; pretreatment of anthocyanins significantly (p < 0.05) enhanced the thymus and spleen indices and spleen cell survival compared to the irradiation control group. Pretreatment with anthocyanins before irradiation significantly reduced the numbers of micronuclei (MN) in bone marrow polychromatic erythrocytes (PCEs). These findings indicate that anthocyanins have immunostimulatory potential against immunosuppression induced by the radiation.
PMCID: PMC3546787  PMID: 23249859
lingonberry; anthocyanins; radioprotection; immunomodulatory
17.  A randomized controlled trial of long term effect of BCM guided fluid management in MHD patients (BOCOMO study): rationales and study design 
BMC Nephrology  2012;13:120.
Bioimpedance analysis (BIA) has been reported as helpful in identifying hypervolemia. Observation data showed that hypervolemic maintenance hemodialysis (MHD) patients identified using BIA methods have higher mortality risk. However, it is not known if BIA-guided fluid management can improve MHD patients’ survival. The objectives of the BOCOMO study are to evaluate the outcome of BIA guided fluid management compared with standard care.
This is a multicenter, prospective, randomized, controlled trial. More than 1300 participants from 16 clinical sites will be included in the study. The enrolment period will last 6 months, and minimum length of follow-up will be 36 months. MHD patients aged between 18 years and 80 years who have been on MHD for at least 3 months and meet eligibility criteria will be invited to participate in the study. Participants will be randomized to BIA arm or control arm in a 1:1 ratio. A portable whole body bioimpedance spectroscopy device (BCM—Fresenius Medical Care D GmbH) will be used for BIA measurement at baseline for both arms of the study. In the BIA arm, additional BCM measurements will be performed every 2 months. The primary intent-to-treat analysis will compare outcomes for a composite endpoint of death, acute myocardial infarction, stroke or incident peripheral arterial occlusive disease between groups. Secondary endpoints will include left ventricular wall thickness, blood pressure, medications, and incidence and length of hospitalization.
Previous results regarding the benefit of strict fluid control are conflicting due to small sample sizes and unstable dry weight estimating methods. To our knowledge this is the first large-scale, multicentre, prospective, randomized controlled trial to assess whether BIS-guided volume management improves outcomes of MHD patients. The endpoints of the BOCOMO study are of utmost importance to health care providers. In order to obtain that aim, the study was designed with very careful important considerations related to the endpoints, sample size, inclusion criteria, exclusion criteria and so on. For example, annual mortality of Beijing MHD patients was around 10%. To reach statistical significance, the sample size will be very large. By using composite endpoint, the sample size becomes reasonable and feasible. Limiting inclusion to patients with urine volume less than 800 ml/day the day before dialysis session will limit confounding due to residual renal function effects on the measured parameters. Patients who had received BIS measurement within 3 months prior to enrolment are excluded as data from such measurements might lead to protocol violation. Although not all patients enrolled will be incident patients, we will record the vintage of dialysis in the multivariable analysis.
Trial registration
Current Controlled Trials NCT01509937
PMCID: PMC3489516  PMID: 23006960
Hemodialysis; Bioimpedance; Dry weight; Body composition monitor; Randomized controlled trial
18.  Mineral and bone disorder in Chinese dialysis patients: a multicenter study 
BMC Nephrology  2012;13:116.
Mineral and bone disorder (MBD) in patients with chronic kidney disease is associated with increased morbidity and mortality. Studies regarding the status of MBD treatment in developing countries, especially in Chinese dialysis patients are extremely limited.
A cross-sectional study of 1711 haemodialysis (HD) patients and 363 peritoneal dialysis (PD) patients were enrolled. Parameters related to MBD, including serum phosphorus (P), calcium (Ca), intact parathyroid hormone (iPTH) were analyzed. The achievement of MBD targets was compared with the results from the Dialysis Outcomes and Practice Study (DOPPS) 3 and DOPPS 4. Factors associated with hyperphosphatemia were examined.
Total 2074 dialysis patients from 28 hospitals were involved in this study. Only 38.5%, 39.6% and 26.6% of them met the Kidney Disease Outcomes Quality Initiative (K/DOQI) defined targets for serum P, Ca and iPTH levels. Serum P and Ca levels were statistically higher (P < 0.05) in the HD patients compared with those of PD patients, which was (6.3 ± 2.1) mg/dL vs (5.7 ± 2.0) mg/dL and (9.3 ± 1.1) mg/dL vs (9.2 ± 1.1) mg/dL, respectively. Serum iPTH level were statistically higher in the PD patients compared with those of HD patients (P = 0.03). The percentage of patients reached the K/DOQI targets for P (37.6% vs 49.8% vs 54.5%, P < 0.01), Ca (38.6% vs 50.4% vs 56.0%, P < 0.01) and iPTH (26.5% vs 31.4% vs 32.1%, P < 0.01) were lower among HD patients, compared with the data from DOPPS 3 and DOPPS 4. The percentage of patients with serum phosphorus level above 5.5 mg/dL was 57.4% in HD patients and 47.4% in PD patients. Age, dialysis patterns and region of residency were independently associated with hyperphosphatemia.
Status of MBD is sub-optimal among Chinese patients receiving dialysis. The issue of hyperphosphatemia is prominent and needs further attention.
PMCID: PMC3507668  PMID: 22994525
End stage renal disease; Mineral and bone disorder; Epidemiology
19.  Comparison of Ultrasonic and CO2 Laser Pretreatment Methods on Enzyme Digestibility of Corn Stover 
To decrease the cost of bioethanol production, biomass recalcitrance needs to be overcome so that the conversion of biomass to bioethanol becomes more efficient. CO2 laser irradiation can disrupt the lignocellulosic physical structure and reduce the average size of fiber. Analyses with Fourier transform infrared spectroscopy, specific surface area, and the microstructure of corn stover were used to elucidate the enhancement mechanism of the pretreatment process by CO2 laser irradiation. The present work demonstrated that the CO2 laser had potential to enhance the bioconversion efficiency of lignocellulosic waste to renewable bioethanol. The saccharification rate of the CO2 laser pretreatment was significantly higher than ultrasonic pretreatment, and reached 27.75% which was 1.34-fold of that of ultrasonic pretreatment. The results showed the impact of CO2 laser pretreatment on corn stover to be more effective than ultrasonic pretreatment.
PMCID: PMC3344206  PMID: 22605970
pretreatment; CO2 laser; ultrasonic; corn stover; FT-IR
20.  Evaluation of Antioxidant and Antiproliferative Properties of Three Actinidia (Actinidia kolomikta, Actinidia arguta, Actinidia chinensis) Extracts in Vitro 
The total phenolic content, total flavonoid content, vitamin C content, and antioxidant activities of ethanol extracts from different kiwifruit varieties (Actinidia kolomikta, Actinidia arguta, Actinidia chinensis) were determined in this study. Multiple scavenging activity assays including the hydroxyl radical, O2−·radical, DPPH, and the ABTS+ radical scavenging activity assays were used to identify the antioxidant activities of Actinidia extracts. The cell viability of HepG2 and HT-29 cells was also examined in this study. The results demonstrated that the Actinidia kolomikta extract had a higher antioxidant activity than the other two Actinidia extracts. There is a positive correlation between antioxidant activity and the polyphenols and vitamin C content in all three extracts (R2 ≥ 0.712, p < 0.05). The Actinidia arguta extract had the highest inhibitory effect on HepG2 and HT-29 cell growth. These results provide new insight into the health functions of fruit and demonstrate that Actinidia extracts can potentially have health benefits.
PMCID: PMC3382775  PMID: 22754311
Actinidia; total phenolic content; flavonoids; antioxidant activity; antiproliferative activity
21.  Increased active von Willebrand factor during disease development in the aging diabetic patient population 
Age  2011;35(1):171-177.
Type 2 diabetes is known to cause endothelial activation resulting in the secretion of von Willebrand factor (VWF). We have shown that levels of VWF in a glycoprotein Ib-binding conformation are increased in specific clinical settings. The aim of the current study is to investigate whether active VWF levels increase during aging and the development of diabetes within the population of patients suffering from type 2 diabetes. Patients and controls were divided into two groups based on age: older and younger than 60 years of age. VWF antigen, VWF propeptide, VWF activation factor and total active VWF were measured. Patients older than 60 years of age had increased levels of total active VWF, VWF activation factor and VWF propeptide compared to younger patients and controls. All measured VWF parameters were associated with age in diabetic patients. Total active VWF and VWF propeptide correlated with the period of being diagnosed with diabetes. Regression analyses showed that especially the VWF activation factor was strongly associated with diabetes in patients older than 60 years of age. In conclusion, we found that the conformation of VWF could be involved in the disease process of diabetes and that the VWF in a glycoprotein Ib-binding conformation could play a role as risk marker during the development of diabetes in combination with an increase in age. Our study shows that the active quality of VWF was more important than the quantity.
PMCID: PMC3543747  PMID: 22120183
Diabetes; Aging; VWF antigen; VWF activation factor; Total active VWF
22.  Particulate Matter Exposure Exacerbates High Glucose-Induced Cardiomyocyte Dysfunction through ROS Generation 
PLoS ONE  2011;6(8):e23116.
Diabetes mellitus and fine particulate matter from diesel exhaust (DEP) are both important contributors to the development of cardiovascular disease (CVD). Diabetes mellitus is a progressive disease with a high mortality rate in patients suffering from CVD, resulting in diabetic cardiomyopathy. Elevated DEP levels in the air are attributed to the development of various CVDs, presumably since fine DEP (<2.5 µm in diameter) can be inhaled and gain access to the circulatory system. However, mechanisms defining how DEP affects diabetic or control cardiomyocyte function remain poorly understood. The purpose of the present study was to evaluate cardiomyocyte function and reactive oxygen species (ROS) generation in isolated rat ventricular myocytes exposed overnight to fine DEP (0.1 µg/ml), and/or high glucose (HG, 25.5 mM). Our hypothesis was that DEP exposure exacerbates contractile dysfunction via ROS generation in cardiomyocytes exposed to HG. Ventricular myocytes were isolated from male adult Sprague-Dawley rats cultured overnight and sarcomeric contractile properties were evaluated, including: peak shortening normalized to baseline (PS), time-to-90% shortening (TPS90), time-to-90% relengthening (TR90) and maximal velocities of shortening/relengthening (±dL/dt), using an IonOptix field-stimulator system. ROS generation was determined using hydroethidine/ethidium confocal microscopy. We found that DEP exposure significantly increased TR90, decreased PS and ±dL/dt, and enhanced intracellular ROS generation in myocytes exposed to HG. Further studies indicated that co-culture with antioxidants (0.25 mM Tiron and 0.5 mM N-Acetyl-L-cysteine) completely restored contractile function in DEP, HG and HG+DEP-treated myocytes. ROS generation was blocked in HG-treated cells with mitochondrial inhibition, while ROS generation was blocked in DEP-treated cells with NADPH oxidase inhibition. Our results suggest that DEP exacerbates myocardial dysfunction in isolated cardiomyocytes exposed to HG-containing media, which is potentially mediated by various ROS generation pathways.
PMCID: PMC3151271  PMID: 21850256
23.  KLF4 Expression Correlates with the Degree of Differentiation in Colorectal Cancer 
Gut and Liver  2011;5(2):154-159.
Krüppel-like factor 4 (KLF4) is an epithelial-specific transcription factor primarily expressed in the gastrointestinal tract that mediates growth arrest in the colonic epithelium. We tried to find whether KLF4 expression is associated with the progression and differentiation of colorectal cancer.
We detected KLF4 expression in 109 colorectal specimens (40 normal appearing mucosa, 7 adenomas, and 62 carcinomas) by immunohistochemistry using a tissue microarray. Western blot and RT-PCR analyses were also performed.
The upregulation of KLF4 expression in carcinoma tissue was statistically significant (p<0.05) when compared to normal appearing mucosa. The negative and weak positive staining rates in normal appearing mucosa, adenoma, and carcinoma were 42.5%, 71.4%, and 82.3%, respectively, indicating a decreased degree of KLF4 expression over the course of progressive transformation of normal cells into malignant derivatives. KLF4 protein levels showed no correlation with sex, age, or metastatic state (p>0.05), while KLF4 protein expression correlated with the diagnostic stage (p<0.05). Furthermore, strong KLF4 staining was detected in 22.9% (11/48) and 0% (0/14) of well/moderately and poorly differentiated colorectal cancers, respectively. Our results clearly indicate that KLF4 protein expression significantly correlates with the degree of differentiation in colorectal cancers (p<0.05). KLF4 expression in RKO cells is also upregulated by butyrate, an inducer of differentiation.
Downregulation of KLF4 expression may lead to more poorly differentiated tumors.
PMCID: PMC3140659  PMID: 21814594
Krüppel-like factor 4; Differentiation; Colorectal cancer; Immunohistochemisty
24.  Low levels of vitamin C in dialysis patients is associated with decreased prealbumin and increased C-reactive protein 
BMC Nephrology  2011;12:18.
Subclinical inflammation is a common phenomenon in patients on either continuous ambulatory peritoneal dialysis (CAPD) or maintenance hemodialysis (MHD). We hypothesized that vitamin C had anti-inflammation effect because of its electron offering ability. The current study was designed to test the relationship of plasma vitamin C level and some inflammatory markers.
In this cross-sectional study, 284 dialysis patients were recruited, including 117 MHD and 167 CAPD patients. The demographics were recorded. Plasma vitamin C was measured by high-performance liquid chromatography. And we also measured body mass index (BMI, calculated as weight/height2), Kt/V, serum albumin, serum prealbumin, high-sensitivity C-reactive protein (hsCRP), ferritin, hemoglobin. The relationships between vitamin C and albumin, pre-albumin and hsCRP levels were tested by Spearman correlation analysis and multiple regression analysis.
Patients were classified into three subgroups by vitamin C level according to previous recommendation [1,2] in MHD and CAPD patients respectively: group A: < 2 ug/ml (< 11.4 umol/l, deficiency), group B: 2-4 ug/ml (11.4-22.8 umol/l, insufficiency) and group C: > 4 ug/ml (> 22.8 umol/l, normal and above).
Patients showed a widely distribution of plasma vitamin C levels in the total 284 dialysis patients. Vitamin C deficiency (< 2 ug/ml) was present in 95(33.45%) and insufficiency (2-4 ug/ml) in 88(30.99%). 73(25.70%) patients had plasma vitamin C levels within normal range (4-14 ug/ml) and 28(9.86%) at higher than normal levels (> 14 ug/ml). The similar proportion of different vitamin C levels was found in both MHD and CAPD groups.
Plasma vitamin C level was inversely associated with hsCRP concentration (Spearman r = -0.201, P = 0.001) and positively associated with prealbumin (Spearman r = 0.268, P < 0.001), albumin levels (Spearman r = 0.161, P = 0.007). In multiple linear regression analysis, plasma vitamin C level was inversely associated with log10hsCRP (P = 0.048) and positively with prealbumin levels (P = 0.002) adjusted for gender, age, diabetes, modality of dialysis and some other confounding effects.
The investigation indicates that vitamin C deficiency is common in both MHD patients and CAPD patients. Plasma vitamin C level is positively associated with serum prealbumin level and negatively associated with hsCRP level in both groups. Vitamin C deficiency may play an important role in the increased inflammatory status in dialysis patients. Further studies are needed to determine whether inflammatory status in dialysis patients can be improved by using vitamin C supplements.
PMCID: PMC3112084  PMID: 21548917
25.  Protective effects of hydrogen-rich saline on monocrotaline-induced pulmonary hypertension in a rat model 
Respiratory Research  2011;12(1):26.
Hydrogen-rich saline has been reported to have antioxidant and anti-inflammatory effects and effectively protect against organ damage. Oxidative stress and inflammation contribute to the pathogenesis and/or development of pulmonary hypertension. In this study, we investigated the effects of hydrogen-rich saline on the prevention of pulmonary hypertension induced by monocrotaline in a rat model.
In male Sprague-Dawley rats, pulmonary hypertension was induced by subcutaneous administration of monocrotaline at a concentration of 6 mg/100 g body weight. Hydrogen-rich saline (5 ml/kg) or saline was administred intraperitoneally once daily for 2 or 3 weeks. Severity of pulmonary hypertension was assessed by hemodynamic index and histologic analysis. Malondialdehyde and 8-hydroxy-desoxyguanosine level, and superoxide dismutase activity were measured in the lung tissue and serum. Levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6) in serum were determined with enzyme-linked immunosorbent assay.
Hydrogen-rich saline treatment improved hemodynamics and reversed right ventricular hypertrophy. It also decreased malondialdehyde and 8-hydroxy-desoxyguanosine levels, and increased superoxide dismutase activity in the lung tissue and serum, accompanied by a decrease in pro-inflammatory cytokines.
These results suggest that hydrogen-rich saline ameliorates the progression of pulmonary hypertension induced by monocrotaline in rats, which may be associated with its antioxidant and anti-inflammatory effects.
PMCID: PMC3065415  PMID: 21375753

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