Characterization and expression analysis of seven lipid metabolism-related genes in yellow catfish Pelteobagrus fulvidraco fed high fat and bile acid diet.

SREBPs, such as SREBP1 and SREBP2, were the key transcriptional factors regulating lipid metabolism. The processing of SREBPs involved many genes, such as scap, s1p, s2p, cideb. Here, we deciphered the full-length cDNA sequences of scap, srebp1, srebp2, s1p, s2p, cideb and cidec from yellow catfish Pelteobagrus fulvidraco. Their full-length cDNA sequences ranged from 1587 to 3884 bp, and their ORF length from 1191 to 2979 bp, encoding 396-992 amino acids. Some conservative domains were predicted, including the multiple transmembrane domains in SCAP, the bHLH-ZIP domain in SREBP1 and SREBP2, the ApoB binding region, ER targeting region and LD targeting region in CIDEb, the LD targeting region in the CIDEc, the conserved catalytic site and processing site in S1P, and the transmembrane helix domain in S2P. Their mRNA expression could be observed in the heart, spleen, liver, kidney, brain, muscle, intestine and adipose, but varied with tissues. The changes of their mRNA expression in responses to high-fat (HFD) and bile acid (BA) diets were also investigated in the brain, heart, intestine, kidney and spleen tissues. In the brain, HFD significantly increased the mRNA expression of seven genes (scap, srebp1, srebp2, s1p, s2p, cideb and cidec), and the BA attenuated the increase of scap, srebp1, srebp2, s1p, s2p, cideb and cidec mRNA expression induced by HFD. In the heart, HFD significantly increased the mRNA abundances of six genes (srebp1, srebp2, scap, s2p, cideb and cidec), and BA attenuated the increase of their mRNA abundances induced by HFD. In the intestine, HFD increased the cideb, s1p and s2p mRNA abundances, and BA attenuated the HFD-induced increment of their mRNA abundances. In the kidney, HFD significantly increased the scap, cidec and s1p mRNA expression, and BA diet attenuated the increment of their mRNA expression. In the spleen, HFD treatment increased the scap, srebp2, s1p and s2p mRNA expression, and BA diet attenuated HFD-induced increment of their mRNA expression. Taken together, our study elucidated the characterization, expression profiles and transcriptional response of seven lipid metabolic genes, which would serve as the good basis for the further exploration into their function and regulatory mechanism in fish.

Electrochemical Ring-Opening of Cyclopropylamides with Alcohols toward the Synthesis of 1,3-Oxazines.

An electrochemical method is presented to construct 1,3-oxazines by the oxidative ring-opening of cyclopropylamides with alcohols. This method avoids the use of external oxidants and thus shows good functional group tolerance. The substrate scope covers primary, secondary, and tertiary alcohols as well as (hetero)aryl amide-substituted cyclopropanes.

Characterization of fifteen key genes involved in iron metabolism and their responses to dietary iron sources in yellow catfish Pelteobagrus fulvidraco.

BACKGROUND: Iron is an essential metal element for organisms, whose metabolism is regulated by many genes and also dietary iron sources. However, the characterization, distribution and the responses of iron metabolism-related genes to different iron sources were not clear in fish. METHODS: The full-length cDNA sequences of fifteen iron metabolism-relevant genes (tf, tfr1, hp, fpn1, ho1, ho2, tfr2, hjv, hepcidin, fth, ftl, ftm, irp1, irp2 and hif2α.) were obtained via 3' and 5' RACE PCR from yellow catfish, a widely distributed freshwater teleost in China and other Asian countries. Their molecular characterizations were analyzed via the bioinformatic methods. Real-time quantitative PCR was used to explore their mRNA distribution in nine tissues. Their mRNA expression responses in four tissues (heart, brain, kidney and gill) were explored in yellow catfish fed diets with five iron sources, including ferrous sulfate (FeSO4), ferrous bisglycinate (Fe-Gly), ferrous chloride (FeCl2), ferric citrate (Fe-CA) and ferric oxide nanoparticles (Fe2O3NPs). RESULTS: Compared with mammals and other teleost, these members shared similar domains. Their mRNAs were expressed in nine tested tissues, but mRNA levels varied. Yellow catfish fed the diets containing Fe-Gly and Fe2O3NPs had higher iron contents in heart, brain, kidney and gill. Meantime, different dietary iron sources addition affected their mRNA expression differentially in brain, heart, kidney and gill. It should be pointed out that only three biological replicate tanks were used in the present feeding treatment, and more biological replicate tanks (more than five) should be emphasized in further researches. CONCLUSION: Taken together, our study identified fifteen iron metabolism-relevant genes, explored their mRNA expression in nine tissues, and their mRNA expression in the responses to different dietary iron sources in four tissues, indicating their important regulatory function in iron metabolism and homeostasis.

The potential pathogenic roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis.

BACKGROUND: The significance of S100A8/A9 and S100A12 in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. This study was dedicated to exploring the potential pathogenic roles of S100A8/A9 and S100A12 in patients with myeloperoxidase (MPO)-ANCA-positive vasculitis. METHODS: Serum and urine concentrations of S100A8/A9 and S100A12 of forty-two AAV patients were evaluated. The influence of S100A8/A9 and S100A12 on the chemotaxis, the apoptosis, the release of IL-1ß, the complement activation, the respiratory burst, as well as the neutrophil extracellular traps (NETs) formation of MPO-ANCA-activated neutrophils was investigated. RESULTS: The serum and urine S100A8/A9 and S100A12 of active MPO-AAV significantly increased (compared with inactive AAV and healthy controls, p < 0.001) and were correlated with the severity of the disease. In vitro study showed that S100A8/A9 and S100A12 activated the p38 MAPK/NF-κB p65 pathway, increased the chemotaxis index (CI) and the release of IL-1ß, extended the life span, and enhanced the complement activation ability of MPO-ANCA-activated neutrophils. The Blockade of TLR4 and RAGE inhibited the effects of S100A8/A9 and S100A12. All above-mentioned effects of S100A8/A9 and S100A12 were ROS-independent because neither S100A8/A9 nor S100A12 enhanced the ROS formation and NETs formation of MPO-ANCA-activated neutrophils. CONCLUSION: S100A8/A9 and S100A12 serve as markers for assessing the disease severity, and they may also play a role in MPO-AAV pathogenesis.

Numerical simulation for spatial distribution of water aerosol produced from nozzle spray and health risk related to Legionella pneumophila in spray scenarios.

Water spray facilities are widely used in public places for sprinkling or beautifying the environment. However, the potential health risk induced by water aerosols increasingly calls for attention. In this study, the spatial distribution of water aerosols was investigated through the molecular sieve adsorption method, and predicted by discrete phase model (DPM). On this basis, the health risk regarding Legionella pneumophila for specific spray scenarios was evaluated by quantitative microbial risk assessment (QMRA). The results showed that the original droplet size can be described by the Rosin_Rommaler distribution (R2>0.99). The spatial distribution of water aerosols produced from a nozzle spray can be well predicted by the DPM. The concentration of water aerosols showed a sharp decline within 5 m from the nozzle and was not significantly different within 5 m (p>0.05) as for various spray scenarios. However, the difference was significant outside 5 m (p<0.05). Furthermore, a safe contact distance of exceeding 8 m is proposed in spray scenarios considering the risk threshold of 0.0001. Sensitivity analysis demonstrated the concentration of Legionella pneumophila in water aerosols as the critical factor affecting the health risk.

Exposure parameters and health risk of Cryptosporidium and Giardia in the recreational water activities for urban residents in China.

Knowledge gaps in the exposure parameters for recreational water activities make quantitative risk assessment related to water recreation difficult. Therefore, the annual exposure frequency and single exposure duration for the recreational water activities of residents from ten cities in the North and South of China were investigated. Questionnaire interviews were carried on recreational water activities comprising swimming (SW), boating (BA), playing in interactive fountains (PF), and watching fountains (WF). Quantitative microbial risk assessment for the exposure of urban residents to Cryptosporidium and Giardia was also performed. For the four recreational water activities, the participation rates of urban residents in SW and WF were higher than the others. For SW and BA, the mean annual exposure frequency and single exposure duration for males were significantly higher than those for females. PF and WF showed the opposite. The annual exposure frequency for above 35-year-old residents was higher than that for young residents (18-35 years). However, the single exposure duration for young residents was highest in SW, BA, and PF. The mean annual exposure frequency and single exposure duration for North China residents were higher than those for South China residents in all recreational water activities, except for SW. Overall, the annual exposure frequency and single exposure duration in recreational water activities for all urban residents followed a lognormal distribution. In the four recreational water activities, the total annual infection risk of male exposure to Cryptosporidium was 1.0 × 10-2, with the confidence intervals between 95 and 5% of [4.3 × 10-4, 3.7 × 10-2], whereas that for females was 6.8 × 10-3 and [4.2 × 10-4, 2.4 × 10-2]. Also, the annual infection risk of males to Giardia was 8.8 × 10-3 and [5.1×10-4, 3.2×10-2], and that of females was 5.3 × 10-3 and [4.0 × 10-4, 1.8 × 10-2]. These results demonstrated that SW and PF made the highest contribution to the total annual infection risk. Sensitivity analysis highlighted that the characterization of exposure parameters plays a critical role in health risk assessment, which may provide a scientific basis for recreational water quality standards formulation.

Monomeric C-reactive protein promotes platelets to release mitochondrial DNA in anti-neutrophil cytoplasmic antibody-associated vasculitis.

Although high level of circulating C-reactive protein (pCRP) is considered as a biomarker for disease activity, the significance of CRP in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. We once reported in AAV, pentameric CRP (pCRP) could dissociate into monomeric CRP (mCRP) and activate platelets. Recent studies have demonstrated that the activated platelets can release mitochondrial DNA (mtDNA). The purpose of this study was to further study the relationship between mCRP and platelets in AAV. We found the plasma level of mCRP in AAV patients was significantly higher than that of normal control and positively correlated with the proportion of mCRP-positive platelets. Platelets isolated from one normal donor could be activated by plasma from 5 AAV patients and this effect could be attenuated when mCRP had been removed. Only 0.1 µg/mL of recombinant mCRP was needed for inducing platelets to release mtDNA via interaction with lipid raft and through p38 MAPK/NF-κB pathway. The mCRP binding on platelets depended on the C-terminal octapeptide (aa 199-206). The released mtDNA did not induce respiratory burst alone, but enhanced the ANCA-induced neutrophils respiratory burst after binding Toll-like receptor 9 (TLR9). The mtDNA released by mCRP-activated platelets also enhanced thrombin generation of plasma. In conclusion, our data demonstrate that mCRP can bind platelets via interaction with lipid raft and induce the release of mtDNA. The released mtDNA can enhance the pathogenicity of ANCA and promote activation of coagulation system in AAV.

Effects and mechanism of platelet-rich plasma on military drill injury: a review.

Military drill injury is a significant part of military medical research. The increase of training intensity and changes in training methods lead to differences in injury types. The ideal therapeutic modality should allow rapid healing at a reasonable cost and minimize impact on patients' life. Platelet -rich plasma (PRP), a platelet concentrate, is rich in a variety of growth factors and widely used clinically as a minimally invasive treatment. It plays an important role in injury repair and rehabilitation. In this article, we review the therapeutic role of PRP in military drill injury and its possible underlying mechanisms, with a focus on plantar fasciitis, stress fractures and other common injuries, in order to provide basic support for military reserve.

Circulating nicotinamide adenine dinucleotide-ubiquinone oxidoreductase chain 6 is associated with disease activity of anti-neutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: Increased serum and urinary mitochondrial DNA have been demonstrated in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Here we investigated the significance of serum nicotinamide adenine dinucleotide-ubiquinone oxidoreductase chain 6 (ND6), which is encoded by mtDNA and can attract neutrophils, in AAV. METHODS: Thirty-seven AAV patients (32 patients with positive myeloperoxidase-ANCA and 5 patients with proteinase 3-ANCA) were enrolled. Relationship between serum ND6 and clinico-laboratory characteristics were analyzed. RESULTS: The ND6 level of patients was higher than normal people (46.56 ± 23.67 pg/mL vs. 4.95 ± 2.45 pg/mL, P < 0.001) The ND6 levels of patients who needed hemodialysis at disease onset and who had pulmonary hemorrhage (PH) were higher than that of the corresponding controls (P = 0.004 and 0.044 respectively). The ND6 level negatively correlated with the percentages of normal glomeruli in kidney biopsy. The AUC of ROC curve to diagnose hemodialysis and PH was 0.804 and 0.750 respectively. ND6 level positively correlated with Birmingham Vasculitis Activity Score in active disease, and returned to normal after remission. Patients with higher serum ND6 had higher mortality (P = 0.023). CONCLUSIONS: Serum ND6 increases in active AAV, and its level correlates with the severity of disease. High ND6 level is associated with severe organ injury and predicts poor prognosis of AAV.

[Sorption of Polybrominated Diphenyl Ethers by Virgin and Aged Microplastics].

The sorption kinetics and isothermal sorption of polybrominated diphenyl ethers (PBDEs) by virgin and aged polyethylene (PE) and polystyrene (PS) microplastics with irradiation by ultraviolet light were studied, with 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) as a representative compound. The influence of different environmental factors, including salinity and dissolved organic matter, on its sorption were analyzed. The virgin and aged microplastics were characterized by scanning electron microscopy, x-ray diffraction, and total reflection infrared spectroscopy. The different models of kinetics and sorption isotherm were used to fit the data, and the sorption mechanism of PBDEs by microplastics was analyzed. The results showed that the main sorption modes of virgin and aged PE were surface sorption and external liquid film diffusion. The virgin and aged PS presented the surface sorption. The sorption isotherm was consistent with the Freudlich model, indicating that the sorption of BDE-47 by microplastics was characterized by a multi-phase, multi-layer, and non-uniform sorption process. The equilibrium sorption capacities of BDE-47 on virgin PE, aged PE, virgin PS, and aged PS were 3.72, 3.76, 6.04, and 3.46 ng·g-1, respectively. There was no obvious difference in equilibrium sorption capacity between the aged and virgin PE. However, the equilibrium sorption capacity for the aged PS was decreased by 42.38% compared with that of the virgin PS. The partition of the outer liquid membrane diffusion was the main mechanism affecting sorption of PBDEs by PE. Compared with the virgin PS, the increase in crystallinity and surface oxygen-containing functional groups led to a decrease in the equilibrium sorption capacity of PBDEs on the aged PS. The sorption of BDE-47 was not significantly influenced by salinity. However, dissolved organic matter exerted a negative effect on the sorption of BDE-47.

Indicatory bacteria and chemical composition related to sulfur distribution in the river-lake systems.

Sulfate related water quality and trophic status are crucial to operation of water diversion. Though the sulfur geochemistry in the lake sediment have been well studied, the effective indicator of surrounding environment conditions related to sulfur in river-lake systems are still unknown. In this study, Dongping Lake (DPH), Weishan Lake (WSH), and Hanzhuang trunk canal (HZQ) were selected as the typical river-lake systems in the eastern of China. Different spatial variations in sedimentary sulfate, total sulfur, and elemental composition of sediments were investigated in these areas. The relatively high sulfate in surface water and sediments appeared in portions of WSH. The biodiversity of HZQ and WSH surface sediments was much higher than that of DPH. Pseudomonas, Acinetobacter, and Thiobacillus were the dominant genera of the river-lake systems. Among the different genera in distribution, genera such as Malikia, Sulfurovum and Lysinibacillus were significantly negatively correlated with sulfur related environmental factors. While the genera such as Pseudomonas, Vogesella and Acinetobacter were significantly positively correlated with these factors. Compared with connectivity in the largest interaction network, bacteria such as Proteus, Acidobacter and Chlorobacteria were identified as indicatory taxa to infer sulfate related conditions in the river-lake systems.

Urinary mitochondrial DNA is a useful biomarker for assessing kidney injury of antineutrophil cytoplasmic antibody -associated vasculitis.

BACKGROUND: The value of urinary mitochondrial DNA (mtDNA) for assessing kidney injury of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) was investigated. METHODS: Thirty-nine kidney biopsy-proved myeloperoxidase (MPO)-ANCA associated AAV patients were enrolled and analyzed. RESULTS: The average urinary mtDNA of patients was significantly higher than that of normal controls (3372.74 ± 1859.72 vs. 474.90 ± 123.59 copy/nmol creatinine, p < 0.001). The patients who needed dialysis at disease onset had the highest levels of urinary mtDNA (5072.23 ± 1302.87 copy/nmol creatinine). Urinary mtDNA positively correlated with urinary neutrophil gelatinase-associated lipocalin (R = 0.661, P < 0.001) and negatively correlated with estimated glomerular filtration rate (R = -0.515, P = 0.001). The urinary mtDNA level of crescentic class (4703.08 ± 1744.31 copy/nmol creatinine) was higher than that of mixed class (3258.14 ± 1158.99 copy/nmol creatinine) and focal class (2268.15 ± 1897.63 copy/nmol creatinine). Univariate correlation analysis showed urinary mtDNA positively correlated with interstitial neutrophils (R = 0.471, P = 0.048) and glomerular neutrophils (R = 0.673, P = 0.002) in kidney biopsy. Among 13 patients who needed hemodialysis at disease onset, 10 patients who got renal recovery had higher urinary mtDNA than 3 patients who remained dialysis dependent (5455.20 ± 1174.64 vs. 3795.67 ± 893.34 copy/nmol creatinine, p = 0.047). CONCLUSIONS: Urinary mtDNA increases in AAV with kidney injury, and its levels correlate with the severity of kidney injury and neutrophils infiltration in pathology.

Pathological severity determines the renal recovery for anti-myeloperoxidase antibody-associated vasculitis requiring dialysis at disease onset: a retrospective study.

BACKGROUND: Many patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) need dialysis at disease onset due to severe kidney injury. Determining whether they can become dialysis independent is an important clinical assessment. METHODS: Forty kidney biopsy-proved myeloperoxidase (MPO)-ANCA associated AAV patients who required dialysis at disease onset were enrolled. Relationships between laboratory and pathological characteristics and prognoses were analyzed. RESULTS: Twenty-five patients obtained dialysis independence within 3 months, while the other 15 patients remained dialysis dependent. No sclerotic class was identified among the 40 patients. Only two biopsies exhibited focal class diagnoses and both these patients recovered their renal function. The renal recovery rate of the 20 patients with mixed class was significantly lower than that of the 18 patients with crescentic class (40.0% vs. 83.3%, p = 0.006). Receiver operating characteristics (ROC) curves showed fibrous crescent+global glomerulosclerosis greater than 32.6% was a strong predictor of dialysis dependence with a sensitivity of 93.3% and specificity of 88.0%. When the percentage of fibrous crescent+global glomerulosclerosis exceeded 47.9%, dialysis independence was not possible. Correlation analysis indicated that platelet counts were negatively correlated with the percentage of fibrous crescent+global glomerulosclerosis (R = -0.448, p = 0.004). Most patients with increased platelets (84.62%) obtained renal recovery. Compared with methylprednisolone pulse therapy, plasma exchange accelerated renal recovery (29.4 ± 15.6 vs. 41.4 ± 11.7 days, p = 0.039). CONCLUSIONS: For MPO-ANCA AAV who required dialysis at disease onset, crescentic and mixed classes accounted for the majority of patients in our cohort. The renal outcome of mixed class patients was worse than that of crescentic class. A high proportion of fibrous crescent+global glomerulosclerosis is a predictor of dialysis dependence. Increased platelet count is associated with active and reversible renal lesions.

Malignant ureteral obstruction: experience and comparative analysis of metallic versus ordinary polymer ureteral stents.

BACKGROUND: To study the outcome and experience of using metallic stents in treating patients with malignant ureteral obstruction (MUO). METHODS: Seventy-six patients with MUO were assigned to the metallic stent group (MSG) or the ordinary polymer stent group (OPSG) according to the different materials. The success rate of the operation, duration of operation, patency rate serum creatinine values ,postoperative complications and QOL scores were compared between the two groups. RESULTS: In the OPSG and MSG, the success rates of the operation were 95.5% and 96.9%, respectively, and the durations of the operation were 20.6 ± 2.2 min and 50.9 ± 10.3 min (P < 0.01), respectively. There was no significant difference between the groups in serum creatinine values at 3 days after the operation (P > 0.05); however, the creatinine values at 3 days after the operation decreased significantly compared with those before the operation (P < 0.01). In the OPSG, there was no significant difference in creatinine values between 3 days and 6 months after operation, while the creatinine values 1 year after operation were increased significantly compared to those at 3 days after the operation (P < 0.05). In the MSG, there was no significant difference among creatinine values at different intervals (P > 0.05). The total rate of post-procedural complication was lower in the MSG than that in the OPSG(P < 0.05). There was no significant difference in the QOL score between the two groups before the operation (P > 0.05); however, the QOL scores at 6 months and 1 year after the operation were higher in the MSG than that in the OPSG(P < 0.05). In the MSG, there was no significant difference in the QOL score between preoperation and 6 months after surgery. Similarly, there was also no difference in the QOL score between 6 months after surgery and 1 year after surgery(P > 0.05). On the contrary, the differences of QOL score in the OPSG group were much significant between disparate time intervals (P < 0.05). CONCLUSIONS: For patients with MUO who require long-term retention of the stent, metallic stents with longer indwelling time are superior to ordinary polymeric stents.

High serum hepcidin is associated with the occurrence of anemia in anti-myeloperoxidase antibody-associated vasculitis with normal kidney function: a cross-sectional study.

The etiology of anemia in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been elucidated. In this cross-sectional study, we tried to investigate the relationship between serum hepcidin and anemia in myeloperoxidase (MPO)-ANCA-AAV. Data of 64 newly diagnosed AAV patients who did not have kidney dysfunction or hemorrhage were analyzed. Serum hepcidin was measured with enzyme linked immunosorbent assay. Twenty-three of 64 patients had anemia. Compared with patients without anemia, patients with anemia had higher Birmingham vasculitis activity score [10 (3, 23) vs. 5 (3, 17), p = 0.020], lower levels of serum iron (5.83 ± 1.63 vs. 9.76 ± 1.54, p < 0.001) and higher levels of ferrtin [358.00 (59.85, 1314.10) vs. 151.05 (43.00, 645.30), p = 0.006]. All 64 patients had increased levels of serum hepcidin compared with normal controls, while patients with anemia had higher serum hepcidin than patients without anemia (85.30 ± 16.92 ng/mL vs. 53.48 ± 13.32 ng/mL, p < 0.001). In the multivariable analysis, the level of hemoglobin correlated with the levels of serum iron (r = 0.344, p = 0.026) and hepcidin (r = - 0.353, p = 0.022). Low level of serum iron was related to high level of serum hepcidin (r = - 0.472, p = 0.001). Immunosuppressive treatment induced rapid decrease of hepcidin and increase of serum iron on the 1st month, while the recovery of hemoglobin was relatively slow. This study indicated that in MPO-AAV without kidney dysfunction or hemorrhage, the existence of anemia is associated with high level of hepcidin which induces low serum iron and the abnormality of iron utilization.

Severe acute interstitial nephritis induced by valsartan: A case report.

RATIONALE: Angiotensin receptor blocker (ARB) can increase serum creatinine or potassium levels in patients with renal insufficiency, renal artery stenosis, heart failure or hypovolemia, but hardly cause severe kidney injury in patients without any risk factors. A case of severe acute interstitial nephritis (AIN) induced by valsartan was reported here. PATIENT CONCERNS: A 62-year-old female with nausea for 1 month and acute deterioration of kidney function for 2 weeks was admitted. She had a history of hypertension for 5 months and had taken valsartan 40 mg daily for 4 months. Although the valsartan had been stopped for 2 weeks, the serum creatinine continuously increased after admission. Kidney biopsy demonstrated the eosinophils infiltration in interstitium. DIAGNOSES: AIN induced by valsartan. INTERVENTIONS: The patient was treated with glucocorticoid. OUTCOMES: The serum creatinine decreased gradually and got back to normal level 5 months later. Then therapy of glucocorticoid was stopped. Renal artery stenosis was excluded by computed tomography angiography (CTA). LESSONS: Although valsartan-induced allergy has been reported previously, AIN was firstly recognized as a severe complication of this drug. We suggest when there is a ARB-associated continuous deterioration of kidney function for patients without renal insufficiency, renal artery stenosis, heart failure or hypovolemia, AIN should be thought of and therapy with glucocorticoid should be considered if necessary.

Clinical and pathologic characteristics of pauci-immune anti-myeloperoxidase antibody associated glomerulonephritis with nephrotic range proteinuria.

BACKGROUND: Heavy proteinuria in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is usually considered to be associated with immune deposits in renal biopsy. Nephrotic ANCA GN without immune deposits (pauci-immune) is rare and has not been studied specially. In this study characteristics of these patients are to be investigated. METHODS: Clinical and pathological characteristics from 20 kidney biopsy-proven pauci-immune anti-myeloperoxidase antibody-associated GN patients with nephrotic proteinuria were analyzed and were compared with ANCA GN patients without nephrotic proteinuria. RESULTS: Acute kidney injury (AKI) and gross hematuria were much prevalent but extra-renal involvement was less prevalent in pauci-immune ANCA GN with nephrotic proteinuria than in pauci-immune ANCA GN without nephrotic proteinuria. No more severe hypoalbuminemia, hypercoagulability, hyperlipidemia or higher thrombosis incidence were found between two groups. Compared with patients without nephrotic proteinuria, patients with nephrotic proteinuria had more prevalent crescentic category in histopathology. Proteinuria decreased quickly after treatment but much poorer renal prognosis was found in pauci-immune ANCA GN with nephrotic proteinuria. The results of urinary albumin to total protein ratio and urinary protein electrophoresis showed pauci-immune ANCA GN with nephrotic proteinuria had obvious non-selective proteinuria. CONCLUSIONS: Pauci-immune ANCA GN with nephrotic proteinuria do not have more severe hypoalbuminemia, hypercoagulability or hyperlipidemia than patients without nephrotic proteinuria. Non-selective proteinuria might be the reason. However, pauci-immune ANCA GN with nephrotic proteinuria have more prevalent crescentic category in histopathology, higher incidence of AKI, gross hematuria and poorer renal prognosis despite of good sensitivity to therapy of proteinuria.

Increased prevalence of peripheral arterial disease in patients with obese sarcopenia undergoing hemodialysis.

Background peripheral arterial disease (PAD) is a common complication in patients undergoing dialysis, which reduces the quality of life and increases the risk of mortality. Recent literature has documented an association between increased visceral fat (VF) content and a proatherogenic factors in end-stage renal disease. The present study investigated the prevalence of PAD in patients undergoing hemodialysis. PAD was determined as an ankle-brachial index <0.9. Additionally, VF content was determined using multiple frequency bioelectrical impendence analysis. The nutritional status of the patients was evaluated by subjective global assessment and endothelial function was measured by ultrasonographic brachial artery flow-mediated dilatation. Patients divided into two groups (malnourished and non-malnourished) with two further subgroups in each (high VF and low VF content). The prevalence of PAD was identified to be significantly higher in patients with a high VF mass compared with a low VF mass in non-malnourished patients. PAD was significantly more common in malnourished patients compared with non-malnourished patients (P<0.01). The presence of PAD in patients undergoing hemodialysis was identified to be significantly correlated with age, diabetes mellitus (DM) status VF content, malnutrition, serum albumin level, diastolic blood pressure and log C-reactive protein levels. Furthermore, logistic regression analysis determined that age, DM, VF content and malnutrition were significant independent risk factors for PAD in patients undergoing hemodialysis. In conclusion, the results of the present study indicated that obesity and malnutrition act synergistically to increase the risk of PAD in patients undergoing dialysis.

Hypoalbuminaemia in antineutrophil cytoplasmic antibody-associated vasculitis: incidence and significance.

OBJECTIVES: Hypoalbuminaemia has been proved to be a biomarker of poor prognosis in many diseases. The objective of this study was to investigate the significance of hypoalbuminaemia in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Data of 117 AAV patients were analysed retrospectively. The relationship between hypoalbuminaemia and disease severity were studied. The influence of albumin on the pathogenetic role of ANCA was investigated in vitro. RESULTS: Among all patients, 52 had light hypoalbuminaemia (30g/L<=albumin<35g/L) and 40 had nephrotic hypoalbuminaemia (albumin <30g/L). Patients with hypoalbuminaemia had higher inflammation levels and more severe kidney injury than patients without hypoalbuminaemia, but no significant difference of the urinary protein levels were found between patients with nephrotic and light hypoalbuminaemia. Multivariate analysis showed serum albumin correlated with age (r=-0.566, p=0.018), C-reactive protein (r=-0.521, p=0.032) and haemoglobin (r=0.512, p=0.036). Patients with nephrotic hypoalbuminaemia had higher incidence of infection, end stage renal disease and all cause mortality during treatment than patients with light hypoalbuminaemia or normal serum albumin. In vitro study indicated albumin could inhibit the binding between ANCA and neutrophils in a concentration dependent manner. Albumin also inhibited the ANCA-induced respiratory burst and neutrophil extracellular traps formation. CONCLUSIONS: Serum albumin have an inhibitory effect on the binding between ANCA and its antigen. The incidence of hypoalbuminaemia in AAV with kidney involvement is high but is not caused by heavy proteinuria. Hypoalbuminaemia is correlated with the high inflammation level and poor prognosis of AAV. Therapy targeting hypoalbuminaemia might benefit patients with AAV.

[Effect of miRNA from Glycyrrhiza uralensis decoction on gene expression of human immune cells].

MicroRNAs(miRNA) are small non-coding RNAs that regulate the expression of protein coding genes by repressing translation of protein coding mRNA or enhancing mRNA degradation. Its functions have attracted more and more attention from the public. In recent years, the cross-border regulation of miRNA has become a new research direction, and provides a new perspective for people to comprehensively understand the functions of miRNA. Plant miRNA is usually methylated and not easy to degrade. According to our previous researches, there were abundant small RNAs in the decoction of dried liquorice, which provides a new way to study the mechanism of action of licorice. In this study, small RNAs extracted from Glycyrrhiza uralensis decoction and synthesized miRNA mimics were used to treat peripheral blood mononuclear cells(PBMC) isolated from healthy volunteers. The gene expression of toll-like receptors(TLRs), some transcription factors, signal molecules and cytokines were analyzed by RT-PCR. The results showed that glycyrrhiza miRNA could significantly regulate PBMC by inhibiting the expression of genes involved in T cell differentiation, inflammation and apoptosis. The study brought new ideas to us in comprehensively studying the mechanism of licorice and developing the traditional Chinese medicine.