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Acute kidney injury (AKI) is a common adverse reaction of the anticancer drug. Among these chemotherapeutic agents, cisplatin, an effective chemotherapeutic drug, is extensively applied to the treatment of solid tumours, yet various adverse reactions, especially AKI, often limit their use. However, the pathogenesis of AKI caused by cisplatin remains poorly clarified. Therefore, we tested whether microRNAs, which have been certified as key regulators of disease are involved in this process. AKI mouse and HK2 cells were treated with cisplatin. Annexin V/PI staining and cleaved caspase-3 were used to assess apoptosis. Western blot analyses and qRT-PCR were used to evaluate the protein and mRNA level of TRPC6 and DRP1. miR-26a was remarkably decreased in cisplatin-induced AKI and in cisplatin co-cultured HK2 cells. Furthermore, we used a miR-26a mimics in vitro and found that apoptosis was alleviated than that in the control cells. We further verified that miR-26a protected against cisplatin-induced cell apoptosis by acting on transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamin-related protein 1 (DRP1), thus inhibited the mitochondrial apoptosis pathway. Therefore, the study unveiled that miR-26a/TRPC6/DRP1 is a novel protective pathway in cisplatin-induced AKI and may be targeted for the prevention and treatment of drug-related renal injury. SIGNIFICANCE OF THE STUDY: Our study found that miR-26a was significantly downregulated during cisplatin-induced AKI and during cisplatin co-cultured HK2 cells. Further, in vitro we used miR-26a mimic to intervene cells and found that apoptosis alleviated compared with control group. We further verified that miR-26a protected cisplatin-induced apoptosis by target transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamic-related protein 1 (DRP1) and inhibit the mitochondrial apoptosis pathway. Thus, miR-26a/TRPC6/DRP1 is a new protective pathway in cisplatin-induced AKI and may be targeted for the prevention and treatment of drug-related acute kidney injury.

Complement factor B (CFB) variants have been described to play a causative role in auto-immune associated C3 glomerulopathy (C3G) and/or atypical hemolytic uremic syndrome (aHUS) by affecting the dysregulations of alternative pathway activation. However, CFB variant concomitant with COL4A5 variant is scarce. Here, we depict two intriguing cases with concurrent novel heterozygosity for CFB c.2054_2057del (p.Ser687Profs∗16) variant and a previous reported COL4A5 c.2999G > T (p.Gly1000Val) variant in a pair of siblings. The clinical feature of either paternal CFB variant or maternal COL4A5 variant is just mild microscopic hematuria. Interestingly, their two children with paternal CFB c.2054_2057del (p.Ser687Profs∗16) variant and maternal COL4A5 c.2999G > T (p.Gly1000Val) variant presented with massive proteinuria, hematuria, and progressive renal failure with poor treatment response. Moreover, complement pathway activation in renal tissue further supports and strengthens the pathogenic role of CFB variant in the development of renal injury in the presence of COL4A5 variant. In conclusion, the rare sibling cases highlight that the extension of genetic analyses in the proband is helpful for the diagnosis and understanding of some family cluster renal diseases.

AIM Lipoprotein(a) [Lp(a)] is considered a risk factor for cardiovascular disease. However, the role of Lp(a) in chronic kidney disease (CKD) patients is not well understood. The aim of this study was to evaluate the association between Lp(a) levels and the presence of coronary artery disease (CAD) and the severity of coronary artery stenosis (CAS) in patients with stage 3-5 CKD. PATIENTS AND METHODS We retrospectively studied patients who were diagnosed with stage 3-5 CKD and underwent coronary artery angiography in Zhongda Hospital. The Gensini scoring system was used to assess the severity of coronary stenosis. RESULTS A total of 1003 patients were enrolled in this cross-sectional study, and 776 of these patients were diagnosed with CAD. The Lp(a) levels were significantly higher in the CAD group than the non-CAD group [271.50 (168.00-459.25) vs. 195.00 (131.00-347.00) mg/l, P

IgA nephropathy (IgAN) features variable renal pathology and a heterogeneous clinical course. Our aim was to search noninvasive biomarkers from urinary exosomes for IgAN patients; membrane nephropathy and minimal change disease were included as other glomerulopathy controls. Transmission electron microscopy and nanoparticle tracking analysis confirmed the size and morphology characteristic of urinary exosomes. Exosome markers (Alix and CD63) as well as renal cell markers [aquaporin 2 (AQP2) and nephrin] were detected, which indicate the renal origin of urinary exosomes. Exosome excretion was increased markedly in IgAN patients compared with controls and correlated with levels of proteinuria and tubular injury. More important, urinary exosome excretion correlated with greater histologic activity (mesangial hypercellularity, crescents, and endocapillary hypercellularity). Profiling of the inflammation-related mRNA revealed that exosomal chemokine (C-C motif) ligand 2 (CCL2) was up-regulated in IgAN patients. In a validation study, CCL2 was exclusively highly expressed in IgAN patients compared with healthy controls as well as minimal change disease and membrane nephropathy patients. Also, a correlation between exosomal CCL2 and estimated glomerular filtration rate levels was found in IgAN. Exosomal CCL2 was correlated with tubulointerstitial inflammation and C3 deposition. High CCL2 levels at the time of renal biopsy were associated with subsequent deterioration in renal function. Thus, urinary exosomes and exosomal CCL2 mRNA are promising biomarkers reflecting active renal histologic injury and renal function deterioration in IgAN.

Artemisinin (Art) is isolated from Artemisia annua L. and known as the most effective antimalaria drugs. Previous studies demonstrated that it could exert an immune-regulatory effect on autoimmune diseases. In this study, we first investigated its potential role in tubulointerstitial inflammation and fibrosis in rats with 5/6 nephrectomy. Subtotal nephrectomized (SNx) rats were orally administered Art (100 mg·kg -1 ·d - 1) for 16 weeks. Blood and urine samples were collected for biochemical examination. Kidney tissues were collected for immunohistochemistry and Western blot analyses. Ang II-induced injury of the human kidney 2 (HK-2) cells was used for in vitro study. It was shown that Art could significantly attenuate the renal function decline in SNx rats compared with control. More importantly, Art treatment significantly reduced the tubulointerstitial inflammation and fibrosis, as demonstrated by the evaluation of renal pathology. Furthermore, Art inhibited the activation of NLRP3 inflammasome and NF-κB in the kidneys. In in vitro study, Art pretreatment could significantly prevent the activation of NLRP3 inflammasome and NF-κB in Ang II-treated HK-2 cells, while BAY11-7082 (an inhibitor of NF-κB) significantly inhibited Ang II-induced NLRP3 inflammasome activation. This study suggested that Art could provide renoprotective role by attenuating the tubulointerstitial inflammation and fibrosis in SNx rats by downregulating the NF-κB/NLRP3 signaling pathway.

The study of parathyroid hyperplasia with bone disease as a critical manifestation of chronic kidney disease-mineral and bone disorders (CKD-MBDs) is challenging due to the lack of a suitable research model. Here, we established a rat model with secondary hyperparathyroidism (SHPT) and bone disease induced by adenine and a high phosphorous diet and analyzed the skeletal characteristics. We performed blood analysis, emission computed tomography (ECT), dual energy X-ray absorptiometry (DEXA), micro-computed tomography (micro-CT), bone histomorphometry, and bone mechanical tests. The CKD rats with SHPT induced by adenine and a high phosphorus diet showed severe abnormalities in calcium and phosphorus metabolism and exhibited parathyroid hyperplasia. The bone mineral density (BMD) of femurs and lumbar vertebrae was significantly lower in the CKD rats than in the control (CTL) rats. The cortical and trabecular bone parameters of femurs showed significant bone loss. In addition, we found decreases in ultimate force, work to failure, stiffness, and elastic modulus in the CKD rats. In conclusion, our findings demonstrated that the CKD rats with SHPT induced by adenine and a high phosphorus diet may serve as a useful model for skeletal analysis in CKD with SHPT.

Inflammation is a major contributor to the pathogenesis of ischemic acute kidney injury (AKI), which complicates the post-operative outcomes of large numbers of hospitalized surgical patients. Hydroxychloroquine (HCQ), a well-known anti-malarial drug, is commonly used in clinical practice for its anti-inflammatory actions. However, little is known about its role in renal ischemia/reperfusion (I/R) injury. In the current study, mice were subjected to I/R injury and HCQ was administered for seven days by gavage prior to surgery. In parallel, HK-2 human renal proximal tubule cells were prophylactically treated with HCQ and then were exposed to hypoxia/reoxygenation (H/R). The results showed that HCQ significantly attenuated renal dysfunction evidenced by blunted decreases in serum creatinine and kidney injury molecular-1 expression and the improvement of HK-2 cell viability. Additionally, HCQ markedly reduced macrophage and neutrophil infiltration, pro-inflammatory cytokine production, and NLRP3 inflammasome activation. Mechanistic studies showed that HCQ could inhibit the priming of the NLRP3 inflammasome by down-regulating I/R or H/R-induced NF-κB signaling. Moreover, HCQ reduced cathepsin (CTS) B, CTSD and CTSL activity, and their redistribution from lysosomes to cytoplasm. CTSB and CTSL (not CTSD) were implicated in I/R triggered NLRP3 inflammasome activation. Notably, we found that HCQ attenuated renal injury through downregulation of CTSB and CTSL-mediated NLRP3 inflammasome activation. This study provides new insights into the anti-inflammatory effect of HCQ in the treatment of AKI.

Gastric cancer is one of the most common malignant tumors of the digestive tract and one of the leading causes of death in patients with malignant tumors worldwide. In recent years, with the deepening of circRNA research, more and more evidence indicates that circRNA plays an important role in the occurrence and development of human malignant tumors. This study firstly conducted a retrospective analysis of the case data of gastric cancer patients who were treated at the Wuwei Cancer Hospital between 2015 and 2017. Subsequently, 18 cases of primary gastric cancer patients and 9 healthy people in Wuwei, Gansu Province were used as controls. The high-throughput microarray technology was used to screen the circRNA expression profiles of healthy and gastric cancer patients, and the expression was expressed by bioinformatics methods. Differential circRNA was used for gene ontology (GO) and KEGG pathway analysis, using its enrichment to predict the relevant biological functions of the differentially expressed circRNA and its involved pathways, and predicting miRNAs interacting with differentially expressed circRNAs, and constructing circRNA-miRNA interaction network. Q-PCR, gene organization microarray and bioinformatics techniques were used to validate candidate differential circRNAs and their linear parental genes and regulatable miRNAs. The results showed that there were 137 circRNAs with significant expression differences (including up-regulation of 67 and down-regulation of 70) in gastric cancer patients, and their differential expression may be related to the occurrence and development of gastric cancer; by GO, KEGG enrichment analysis and Regulating miRNA predictive analysis, the gastric cancer-related GO classification, KEGG Pathway and circRNA-miRNA network were preliminarily obtained, suggesting that differential circRNA may participate in gastric cancer-associated GO classification and KEGG pathway by regulating the expression of parental genes and miRNAs to influence the occurrence and development of gastric cancer. Finally, by using has verified the has_circ_0000437 and its parental genes and regulatable miRNAs, it was found that has_circ_0000437 is highly expressed in gastric cancer patients, and has a certain diagnostic value for the clinical diagnosis of gastric cancer. It may regulate its linear parental gene and The expression of miRNAs affects the development, metastasis and prognosis of clinical gastric cancer.

The aim of this study was to detect the spectrum of complement activation pathways in circulation and to assess their correlations with clinical and pathologic features in a large lupus nephritis cohort from China.Plasma levels of C1q, mannose-binding lectin, C4d, Bb, C3, C3a, C5a and soluble C5b-9 were detected by enzyme-linked immunosorbent assay in 222 patients with active biopsy-proven lupus nephritis, 34 patients with lupus nephritis at remission, 82 patients with active systemic lupus erythematosus without renal involvement and 39 normal controls. The correlations between levels of complement components and clinicopathological features of these patients were further analyzed.Plasma levels of C1q and C3 significantly decreased, and the levels of Bb, C3a, C5a and soluble C5b-9 were significantly elevated in patients with active lupus nephritis compared with those in remission, active systemic lupus erythematosus without renal involvement group and normal controls. In the lupus nephritis group, soluble C5b-9 levels were inversely correlated with C1q and C4d levels (r = -0.412, P0.001 and r = -0.221, P = 0.002, respectively), but more strongly correlated with the level of Bb (r = 0.546, P0.001). C3b, Bb and C5b-9 could colocalize on glomeruli in lupus nephritis. Plasma Bb level was significantly correlated with some renal disease activity indices and was a risk factor for renal outcomes (hazard ratio = 1.745; 95% CI: 1.106-2.754; P = 0.017) in the lupus nephritis group.Our findings suggested that the activation of the complement alternative pathway might play a more important role in the pathogenesis of lupus nephritis, and factor Bb might be a useful marker for evaluating renal disease activity and outcomes.

Increasing evidences have demonstrated that the activation of the alternative complement pathway is crucial for the pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Our recent study found that circulating levels of complement factor H (FH), a key regulator of the alternative pathway, were associated with disease activity. In the current study, functional activities of FH were assessed to further explore the potential role of FH in the pathogenesis of AAV. We found that the two patients with ANCA-negative pauci-immune necrotizing crescentic glomerulonephritis exhibited relatively normal functional activities of FH. However, patients with ANCA-positive vasculitis exhibited deficient functional activities of FH, in terms of interaction with and the regulation of C3b, binding to mCRP and endothelial cells, and the protection of host cells against complement attack. Our findings indicate that functional activities of FH are deficient in patients with ANCA-positive vasculitis, potentially contributing to the disease development.

Objective To investigate the protective effect of Astragalus-Lily Granules on intestinal mucosa and intestinal flora homeostasis in mice under high altitude hypoxia condition. Methods We put mice into high altitude hypoxia cabin to establish high altitude hypoxia model mice. Sixty Kunming mice were randomly divided into control group, model group, Astragalus-Lily particles (ALP) low, medium and high dose groups [1.75, 3.5, 7g/(kg•d)] respectively. After three days of routine feeding, the ALP mice received drug by intragastric administration, once a day for continuous 17 days，control group and model group were given double distilled water in same volume. From the 15th day, all the mice but control group were exposed to simulated high altitude hypoxia condition for 3 days in a high altitude hypoxia cabin after they were gavaged for half an hour daily. By the 18th day, the fresh mouse feces were collected and smeared to observe the changes of microflora. The pathological changes of intestinal tissues were observed by HE staining and the expression of HIF-1αprotein in intestines was detected by immunohistochemistry. Results The enterococci and gram negative bacteria showed a higher proportion (65.2%±2.4% and 56.7%±3.3%, respectively) in the model group compared with the control group (24.7%±1.2%, 23.2%±1.5%, respectively, P

On the basis of endocrine therapy for patients with low burden metastatic prostate cancer (LBMP), the clinical efficacy and quality of life were compared between prostate-only directed radiotherapy (PODT) and prostate and metastasis radiotherapy (PMRT). From November 2009 to November 2015, total 91 patients newly diagnosed with LBMP were retrospectively analyzed, of which 52 patients received PODT and 39 patients received PMRT. The biochemical failure free interval (IBF), prostate specific survival (PCSS), and overall survival (OS) time were compared between the 2 groups, and expanded prostate cancer index composite (EPIC) scale was used to evaluate the difference in quality of life between the 2 groups. The median IBF of the PODT group was 31 months, which was significantly lower than the 39 months of the PMRT group (P .05); the side effects of acute radiotherapy in PMRT group were significantly higher than PODT group (P .05). Patients with LBMP receiving PMRT can improve IBF, but cannot increase PCSS and OS, and increase the incidence of acute radiation injury.

316: F1006–F1015, 2019. First published March 6, 2019; doi: 10.1152/ajprenal.00413.2018 .—Experimental studies have shown that pharmacological activation of calcium-sensing receptor (CaSR) attenuates renal fibrosis in some animal models beyond modification of bone and mineral homeostasis; however, its underlying mechanisms remain largely unknown. Since excessive collagen deposition is the key feature of fibrosis, the present study aimed to examine whether CaSR was involved in the regulation of collagen expression in rats with adenine diet-induced renal fibrosis and in profibrotic transforming growth factor (TGF)-β1-treated renal proximal tubular epithelial cells (PTECs). The results showed that the CaSR agonist cinacalcet significantly attenuated renal collagen accumulation and tubular injury in adenine diet-fed rats. Additionally, the in vitro experiment showed that profibrotic TGF-β1 significantly increased the expression of collagen and decreased CaSR expression at the mRNA and protein levels in a concentration- and time-dependent manner. Furthermore, the CaSR CRISPR activation plasmid and cinacalcet partially abrogated the upregulation of collagen induced by TGF-β1 treatment. Blockade of CaSR by the CRISPR/Cas9 KO plasmid or the pharmacological antagonist Calhex231 further enhanced TGF-β1-induced collagen expression. Mechanistic experiments found that Smad2 phosphorylation and Snail expression were markedly increased in PTECs treated with TGF-β1, whereas the CaSR CRISPR activation plasmid and cinacalcet substantially suppressed this induction. In summary, this study provides evidence for a direct renal tubular epithelial protective effect of CaSR activation in renal fibrosis, possibly through suppression of collagen expression in PTECs.

Although glucocorticoids are the mainstays in the treatment of renal diseases for decades, the dose dependent side effects have largely restricted their clinical use. Microvesicles (MVs) are small lipid-based membrane-bound particles generated by virtually all cells. Here we show that RAW 264.7 macrophage cell-derived MVs can be used as vectors to deliver dexamethasone (named as MV-DEX) targeting the inflamed kidney efficiently. Methods: RAW macrophages were incubated with dexamethasone and then MV-DEX was isolated from the supernatants by centrifugation method. Nanoparticle tracking analysis, transmission electron microscopy, western blot and high-performance liquid chromatography were used to analyze the properties of MV-DEX. The LC-MS/MS was applied to investigate the protein compositions of MV-DEX. Based on the murine models of LPS- or Adriamycin (ADR)-induced nephropathy or in-vitro culture of glomerular endothelial cells, the inflammation-targeting characteristics and the therapeutic efficacy of MV-DEX was examined. Finally, we assessed the side effects of chronic glucocorticoid therapy in MV-DEX-treated mice. Results: Proteomic analysis revealed distinct integrin expression patterns on the MV-DEX surface, in which the integrin αLβ2 (LFA-1) and α4β1 (VAL-4) enabled them to adhere to the inflamed kidney. Compared to free DEX treatment, equimolar doses of MV-DEX significantly attenuated renal injury with an enhanced therapeutic efficacy against renal inflammation and fibrosis in murine models of LPS- or ADR-induced nephropathy. In vitro, MV-DEX with about one-fifth of the doses of free DEX achieved significant anti-inflammatory efficacy by inhibiting NF-κB activity. Mechanistically, MV-DEX could package and deliver glucocorticoid receptors to renal cells, thereby, increasing cellular levels of the receptor and improving cell sensitivity to glucocorticoids. Notably, delivering DEX in MVs significantly reduced the side effects of chronic glucocorticoid therapy (e.g., hyperglycemia, suppression of HPA axis). Conclusion: In summary, macrophage-derived MVs efficiently deliver DEX into the inflamed kidney and exhibit a superior capacity to suppress renal inflammation and fibrosis without apparent glucocorticoid adverse effects. Our findings demonstrate the effectiveness and security of a novel drug delivery strategy with promising clinical applications.

Problem Postpartum atypical hemolytic uremic syndrome (aHUS) is a life-threatening syndrome with unclear pathogenesis. The current study aimed to investigate the clinical and pathological features, complement activation status, and the genetic variations in a Chinese cohort of patients with renal biopsy-proven postpartum aHUS. Method of study Five patients with postpartum aHUS were recruited. Renal biopsy specimens were examined and scored. Plasma levels of complements were detected, and coding sequences of complement regulators were screened. Anti-CFH/CFI autoantibodies were further detected. Results Patients with postpartum aHUS patients presented with severe clinical manifestations and renal involvement. The renal biopsies of the five patients showed typical features of thrombotic microangiopathies. The levels of the following complement components, C4d, Bb, C3a, C5a, and SC5b-9, were significantly elevated in patients with postpartum aHUS compared with normal non-pregnant controls. The plasma levels of CFH and CFI significantly decreased in patients with postpartum aHUS compared with normal pregnant women. Three CFH single nucleotide polymorphisms (SNPs) were identified in the five patients. Two patients presented with CFH autoantibodies. Conclusion Postpartum aHUS is a clinical syndrome with severe renal damage. Genetic deficiencies and autoantibodies of CFH may lead to alternative pathway overactivation and participated in the pathogenesis of postpartum aHUS.

High-Cr cast-penetrated layer contained nanometer ceramic particles was formed on the surface of the medium carbon steel ZG250-470 by adding nanoTiN intermediate alloy powder to cast-penetrated agent. Microstructure and wear resistance of the strengthened cast-penetrated layer were studied. The results showed that: compared with not adding intermediate alloy, there were finer and more uniform microstructure and better high temperature and high speed wear performance of strengthened cast-penetrated layer strengthened by nanoTiN intermediate alloy. Strengthening effect would be best by adding the intermediate alloy containing rare earth. By adding intermediate alloy containing Ni, the best high temperature wear resistance of cast-penetrated layer could be obtained.

Objective The interaction between neutrophils and activation of alternative complement pathway plays a critical role in the pathogenesis of ANCA-associated vasculitis (AAV). MPO, which can be released from ANCA-stimulated neutrophils, was recently demonstrated to be capable of activating the alternative complement pathway. Here we aimed to investigate the interaction between MPO and factor H (FH), a key regulator of the alternative pathway, and its effect on the functional activities of FH. Methods Detection of FH and MPO on neutrophil extracellular traps (NETs) induced by serum from AAV patients and in kidney biopsies of AAV patients was performed by immunostaining. In vitro binding between MPO and FH was examined by ELISA and surface plasmon resonance. The influence of MPO on the complement regulatory activity of FH was further assessed. Results FH deposited and co-localized with MPO in NETs. In kidney biopsies from AAV patients, MPO was closely adjacent to FH in glomerular capillaries. We demonstrated that MPO binds to FH with an apparent nanomolar affinity and identified short consensus repeats 1-4 of FH as the major binding sites. In terms of functional analysis, MPO inhibited the interaction between FH and C3b and the decay-accelerating activity of FH. The fluid phase and surface cofactor activities of FH upon C3b inactivation were inhibited by MPO. Conclusion Our findings indicate that MPO binds to FH and influences the complement regulatory activity of FH. MPO-FH interaction may participate in the pathogenesis of AAV by contributing to activation of the alternative complement pathway.

Background Different sensitivity of advanced cervical cancer to irradiation can decrease effectiveness of radiotherapy in some cases. We attempted to identify the differentially expressed genes in residual cervical cancer after radiotherapy that might be associated with poor prognosis and radioresistance. Material/Methods Differential genes expression was identified by an oligonucleotide microarray in cervical cancer tissues before radiation and after a 50-Gy dose of radiation. The microarray results were validated by quantitative real-time PCR. CXCL12 was validated by immunohistochemistry in paraffin-embedded cervical cancer tissues before radiotherapy. The relationship between the differentiated gene and prognosis was validated by survival analysis. Results Hierarchic cluster analysis identified 238 differentiated genes that exhibited ≥3.0-fold change and p

OBJECTIVE: To investigate the effects of vasoactive intestinal peptide (VIP) on the airway inflammation and its regulatory effect on Th17/Treg imbalance in asthmatic mice. METHODS: A total of 30 BALB/c mice were equally and randomly divided into three groups:control, asthma, and VIP. An acute asthmatic mouse model was established by sensitization and challenge with ovalbumin (OVA). The control group received normal saline instead of OVA. Before the challenge with OVA, the VIP group was administered VIP (20 μg/mL) by aerosol inhalation for 30 minutes. The bronchoalveolar lavage fluid (BALF) and the lung tissue were collected from mice. The pathological changes in the lung tissue were observed by hematoxylin and eosin staining. The levels of Th17/Treg-related cytokines in BALF were measured by enzyme-linked immunosorbent assay. The expression of retinoid-related orphan receptor gamma t (RORγt) and forkhead box P3 (Foxp3) were measured by real-time fluorescence quantitative PCR and immunohistochemistry. RESULTS: The histopathological results showed that the VIP group had milder symptoms of airway inflammation than the asthma group. The level of IL-17 in BALF in the asthma group was significantly higher than that in the control group and the VIP group (P < 0.01), but the level of IL-17 in the control group was significantly lower than that in the VIP group (P < 0.01). The level of IL-10 in BALF in the asthma group was significantly lower than that in the control group and the VIP group (P < 0.01, but the level of IL-10 in the VIP group was significantly higher than that in the control group (P < 0.01). The asthma group showed significantly higher expression levels of RORγt mRNA and protein in the lung tissue and significantly lower expression levels of Foxp3 mRNA and protein than the control group (P < 0.01). The VIP group had significantly lower expression levels of RORγt mRNA and protein in the lung tissue and significantly higher expression levels of Foxp3 mRNA and protein than the asthma group (P < 0.05). CONCLUSIONS: The Th17/Treg imbalance may be closely related to the airway inflammation in asthmatic mice. VIP can improve airway inflammation by regulating the Th17/Treg imbalance in asthmatic mice.

Background and Aim Recent studies have shown that imbalance between tumor-infiltrating interleukin (IL)-17+ T cells and regulatory T cells (Tregs) is an important regulator of progression in various cancers, but little is known regarding this imbalance in hepatocellular carcinoma (HCC). This study explored the role of imbalance between IL-17+ T cells and Tregs in the immunopathogenesis of HCC in patients with chronic hepatitis B (CHB) infection. Methods Fifty-six of patient-matched tumors and peritumoral surgical specimens from 56 patient with HCC and 136 liver biopsies specimens from 46 patients with CHB, 37 with atypical hyperplasia (AH), and 53 with HCC were enrolled. The expressions of IL-17, FoxP3, CD4, and CD8 in liver tissue were measured by immunochemistry for the evaluation of liver-infiltrating lymphocytes. Results The density of liver infiltrated FoxP3+ Tregs was increased in a stepwise manner from CHB to AH then HCC, while there was a decreasing trend for the density of IL-17+ T cells and CD8+ T cells. In surgical specimens of less differentiated HCC, the quantity of tumor-infiltrating FoxP3+ Tregs was significantly lower and IL-17+ T cells and CD8+ T cells were significantly higher. Additionally, peritumoral IL-17+ T cells were increased in poorly differentiated HCC. High intratumoral FoxP3+ Tregs with high intratumoral IL-17+ T cells showed a significantly lower overall survival (OS) and disease-free survival (DFS) compared with other groups (OS, P = 0.033; DFS, P = 0.004). High intratumoral FoxP3+ Tregs with high peritumoral IL-17+ T cells showed a significantly lower survival rate compared with other groups (OS, P

The grain size of W-Cu nanocomposites would greatly affect the density of W-Cu alloy. In this work, W-Cu oxide nanocomposite powders were prepared by sodium tungstate and copper nitrate via hydrothermal method, and W-Cu nanocomposite powders were obtained by subsequently co-reduction process. The characterization of W-Cu nanocomposite powders were carried out by X-ray diffraction (XRD), scanning electron microscope (SEM), energy spectrum analysis (EDS) and transmission electron microscope (TEM). The results indicated that hydrothermal method was a good method for the preparation of W-Cu oxide nanocomposite powders. W-Cu nanocomposite powders, whose grain size was about 70nm and distributed uniformity, were manufactured by co-reduction process.

MicroRNAs are a class of small noncoding RNA which play important regulatory roles in a variety of cancers. MiRNA-specific expression profiles have been reported for several pathological conditions. In this study, we combined large scale parallel Solexa sequencing to identify 11 up-regulated miRNAs and 19 down-regulated miRNAs with computational techniques in the sera of ovarian cancer patients while using healthy serum as the control. Among the above, four miRNAs (miR-22, miR-93, miR-106b, miR-451) were validated by quantitative RT-PCR and found to be significantly aberrantly expressed in the serum of ovarian cancer patients (P

Objective. To assess clinicopathological characteristics of lupus nephritis patients with scanty immune deposits.Methods. The data of patients with scanty immune deposits lupus nephritis were retrospectively analyzed. Plasma ANCA and complement components were detected.Results. Among 316 cases with renal biopsy-proven lupus nephritis, 40 cases were diagnosed as scanty immune deposits. There were significantly higher value of serum creatinine (P=0.002) and lower hemoglobin level (P=0.009) and higher score of cellular crescents (P=0.015) in scanty immune deposits group compared with immune complex deposits group. The frequency of positive plasma ANCA was significantly higher in scanty immune deposits group than that in immune complex deposits group (52.5% versus 10.1%,P<0.001). As for comparisons of plasma complement components, there were significantly higher levels of C1q (P=0.005) and Bb (P=0.02) and lower level of factor H (P=0.003) in scanty immune deposits group. The ratio of treatment failure was significantly higher in scanty immune deposits group than that in immune deposits group (42.5% versus 19.20%,P=0.001). The renal outcomes were similar between the two groups.Conclusions. Patients with scanty immune deposits lupus nephritis had more severe kidney damage. ANCA and activation of complement alternative pathway might be involved in the pathogenesis of the disease.

A highly sensitive electrochemical sensor was fabricated by electropolymerizing p-aminobenzene sulfonic acid (ABSA) on quaternary amine functionalized multi-wall carbon nanotubes (Q-MWNTs) modified glassy carbon electrode (GCE). Q-MWNTs provide a conductive and stable network for the poly-ABSA (PABSA) immobilization. The voltammetric behaviors of methotrexate (MTX) and calcium folinate (CF) at the PABSA/Q-MWNTs/GCE were investigated by cyclic voltammetry (CV). Compared with bare GCE, Q-MWNTs/GCE and PABSA/GCE, the PABSA/Q-MWNTs/GCE exhibited excellent electrocatalytic oxidation toward MTX and CF. Separation of the oxidation peak potentials for MTX and CF was 0.26 V in phosphate buffer solution (pH 7.0), which made it suitable for simultaneous determination of these two compounds by differential pulse voltammetry (DPV). Under the optimized conditions, the anodic peak current of MTX was linear with the concentration from 0.1 to 8.0 μM in the presence of 8.0 μM CF, with a detection limit of 0.015 μM (S/N = 3). At the same time, the anodic current of CF was linear with the concentration from 0.1 to 6.5 μM with a detection limit of 0.020 μM in the presence of 8.0 μM MTX. The proposed sensor showed advantages of simple preparation, high sensitivity, good reproducibility and stability. It was successfully applied to simultaneous determination of MTX and CF in urine samples.

Aim Serum Golgi protein 73 (sGP73) is a novel biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in the progression of benign liver diseases to precancerous lesions and HCC. This study aimed to investigate GP73 expression and its correlation with clinicopathological parameters. Methods Tissue GP73 (tGP73) levels were detected in specimens of group A (n = 186) including HCC, peritumoral tissue (PTL), high/low-grade hepatic atypical hyperplasia (AH), chronic hepatitis B (CHB) and normal controls (NC) by immunohistochemistry, and GP73 expression in group B (n = 159) and group C (n = 16) were detected by reverse transcription polymerase chain reaction and western blot, respectively. sGP73 levels were detected in subjects of group D (n = 287) by enzyme-linked immunoassay. Results GP73 expression increased gradually from NC, CHB, PTL to high-grade AH and HCC at both protein and mRNA levels (P

Background Polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene can affect disease progression in HBV infection. However, the results from different reports are inconsistent. The aim of this study was to investigate the association between the MTHFR C677T polymorphism and the outcome of HBV infection in a Tianjin Han population. Methods TaqMan SNP genotyping was employed to determine the alleles and genotypes of MTHFR C677T in 2511 subjects from various stages of HBV infection and 549 healthy controls. Results Of the 3060 subjects, the genotypic frequencies were CT 48.9%, TT 29.3% and CC 21.8%; the allelic frequencies were T 53.8% and C 46.2%. There was no significant difference in genotypic or allelic distribution among the different disease groups. When either healthy subjects or self-limited subjects were used as controls, the TT genotype and the T allele conferred protective effects against hepatocellular carcinoma (HCC) (HCC vs healthy subjects: OR = 0.588, 95% CI = 0.413–0.836, P = 0.003; OR = 0.768, 95% CI = 0.645–0.915, P = 0.003, respectively. HCC vs self-limited subjects: OR = 0.598, 95% CI = 0.404–0.886, P = 0.010; OR = 0.772, 95% CI = 0.635–0.940, P = 0.010, respectively). After sub-stratification by gender, the prevalence of the TT genotype or T allele was the lowest in the male HCC group (TT 23.5%, T 49.8%). The protective effects of the TT genotype and the T allele were observed in male HCC and cirrhotic subjects (HCC vs self-limited subjects: OR = 0.470, 95% CI = 0.288–0.766, P = 0.002; OR = 0.681, 95% CI = 0.535–0.866, P = 0.002, respectively. Liver cirrhosis vs self-limited subjects: OR = 0.624, 95% CI = 0.392–0.992, P = 0.046; OR = 0.791, 95% CI = 0.627–0.998, P = 0.048, respectively), but not in female. When the subjects were stratified according to the clinical features, no statistically significant difference in the genotypic distribution was observed ( P > 0.05). Conclusions The TT genotype and T allele of MTHFR C677T may confer a protective effect on disease progression to HCC in HBV-infected individuals, especially among male patients, in a population with a high prevalence of this genetic marker.

Hemp haulm is processing residues extracted after the hemp fiber, with wide raw material sources, cheap price, light quality, good fiber shapes, good toughness, high strength and good buffer performance. In order to develop the application field of hemp stalk processing residues, cushioning packaging materials were prepared using hemp haulm as raw material with the hybrid inorganic foaming agent and corn starch adhesive by microwave foaming method. The properties including density, foam distribution and static compressive properties of this material were analyzed. The experimental results indicated that the density of hemp haulm foaming cushioning packaging materials was 0.235-0.339g/cm3, cell numbers were 14-25.5/cm2, and rebound rate was 62.2%-93.1%. The major influence factors on the properties of hemp haulm foam material were the particle size, foaming agent and adhesives, etc. Research showed while the hemp haulm diameter was small, the ratio of hemp haulm power and starch was 1:0.4 and starch with polyvinyl alcohol (PVA) was 1:0.5, the materials had good buffer performance. When the ratio of compound foaming agent(sodium bicarbonate, ammonium bicarbonate, ammonium carbonate)was 1:2:1, the material had the best cushioning properties as well as higher strength. Compared with polyethylene (EPE) and polystyrene (EPS), the hemp foam material was harder than EPS with no obvious yield point, no material collapsing and good cushioning properties. When the stress was greater than 5-15 N/cm2, the cushioning property of the hemp haulm foaming material was better than EPE, but close to EPS.

OBJECTIVE The aim of this study was to investigate serum complement factor H (CFH) and its associations with clinical and pathological features in patients with LN. METHODS Serum CFH was detected in 241 LN patients, 38 active and 11 inactive patients with SLE without clinical evidence of renal involvement and 51 normal controls. Serum CFH autoantibodies and CFH Tyr402His were screened in the 241 LN patients. CFH deposition in kidneys was detected in some patients. RESULTS Serum CFH levels in patients with LN at active phase were significantly lower than in 38 SLE patients or in normal controls. No serum anti-CFH autoantibodies were detected in patients with LN, and there was no significant difference in CFH Tyr402His distribution between patients with LN and normal controls. Glomerular expression of CFH was stronger than in normal controls. Serum CFH levels were mildly negatively associated with SLEDAI scores (r = -0.204, P = 0.001) and positively associated with serum C3 (r = 0.367, P < 0.001) and haemoglobulin levels (r = 0.193, P = 0.003). Patients with LN class III, subclass IV-S and those with thrombotic microangiopathy had the lowest serum CFH. CONCLUSION Serum CFH levels were associated with disease activity of LN.

The diagnostic value of combining glypican-3 (GPC3) and CD34 staining for small nodules in liver biopsy specimens has not been evaluated. In this study, 201 thin-core biopsy specimens were assessed using GPC3 and CD34 immunochemical staining, including 33 cirrhotic regenerative nodules, 31 high-grade dysplastic nodules, 70 hepatocellular carcinomas (HCCs) with nodules 3 cm or smaller, and 67 HCCs with nodules larger than 3 cm. The results showed that the accuracy of GPC3 staining (90.3%) among liver nodules 3 cm or smaller was better than its use among all nodules (P = .045). Furthermore, the positive expression rate of costaining was significantly greater than that observed for GPC3 or CD34 single staining (P < .001 and P = .002, respectively).These data demonstrate that GPC3 staining is more accurate for the diagnosis of HCC on thin-core biopsy specimens in nodules 3 cm or smaller compared with its use in all nodules, while GPC3 and CD34 costaining has better diagnostic value than does single staining.

The cross-reactive antigen(s) of tubulointerstitial nephritis and uveitis (TINU) syndrome from renal tubulointerstitia and ocular tissue remain unidentified. The authors' recent study demonstrated that the presence of serum IgG autoantibodies against modified C-reactive protein (mCRP) was closely associated with the intensity of tubulointerstitial lesions in lupus nephritis. The study presented here investigates the possible role of IgG autoantibodies against mCRP in patients with TINU syndrome.mCRP autoantibodies were screened by ELISA with purified human C-reactive protein in 9 patients with TINU syndrome, 11 with drug-associated acute interstitial nephritis, 20 with IgA nephropathy, 19 with minimal change disease, 20 with ANCA-associated vasculitis, 6 with Sjogren's syndrome, and 12 with amyloidosis. mCRP expression was analyzed by immunohistochemistry in renal biopsy specimens from the 9 patients with TINU syndrome and 40 from disease controls. Frozen normal human kidney and iris were used to demonstrate co-localization of human IgG and mCRP from patients with TINU syndrome with laser scanning confocal microscopy.The mCRP autoantibodies were detected in all nine patients with TINU syndrome, significantly higher than that of those with disease controls (P0.05). The renal histologic score of mCRP in TINU syndrome was significantly higher than that in disease controls (P0.05). The staining of mCRP and human IgG were co-localized in renal and ocular tissues.It is concluded that mCRP might be a target autoantigen in TINU syndrome.

Background CD62P is a platelet α-granule membrane protein, and P10 is a platelet membrane glycoprotein thrombospondin. To better understand the effects of hemodialysis (HD), we have conducted this study to investigate CD62P and P10 in assessing the efficacy of HD in treating patients with end-stage renal disease (ESRD). Methods The case group consisted of 111 patients suffering ESRD treated with regular HD and the control group enrolled 117 healthy subjects. Before and after HD treatment, a series of parameters were observed, based on which, CD62P and P10 levels were detected in the patients in two groups before and after HD therapy. The correlation analysis analyzed the correlations of CD62P and P10 markers with serum creatinine (Scr), blood urea nitrogen (BUN), and subjective score; and logistic regression analysis was performed to reveal factors affecting the efficacy of HD. Results BUN, Scr, serum phosphorus, intact parathyroid hormone (iPTH), fibrinogen, and β2-microglobulin (β2-MG) decreased while hemoglobin, albumin, and activated partial thromboplastin time increased in the patients suffering ESRD; patients presented with improvements in subjective symptoms and an increase in dry weight. CD62P and P10 levels were lower in post-treatment patients. CD62P and P10 positively correlated with Scr, BUN and subjective score; post-treatment CD62P and P10 levels, BUN, hemoglobin, albumin, triglyceride, iPTH, β2-MG, and fibrinogen were correlated with the efficacy of HD. Conclusion CD62P and P10 might be correlated to the efficacy of HD in treating ESRD, in turn providing predictive markers for assessing the ability of HD in treating ESRD.

The persistence of covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) in hepatocytes plays a key role in viral persistence and resistance to therapy. Therefore, quantitative cccDNA measurement is of clinical importance for evaluating the efficacy of antiviral drugs, selecting an appropriate treatment strategy, and predicting the prognosis. Current established methods for measurement of cccDNA need further improvement. A modified method was developed using digestion with restriction endonucleases that do not recognize sites in the HBV DNA and plasmid-safe ATP-dependent DNase (PSAD), and using a cccDNA-specific primer set in a real-time PCR reaction. The cccDNA-specific primer has a similar amplification efficiency as a commercial kit. Treatment of samples with restriction endonuclease followed by PSAD digestion increased significantly the specificity of a cccDNA-selective primer set compared with other treatments (P

Plants show different growth responses to N sources supplied with either NH + 4 or NO − 3 . The uptake of different N sources also affects the rhizosphere pH and therefore the bioavailability of soil phosphorus, particularly in alkaline soils. The plant growth, P uptake, and P availability in the rhizosphere of oat ( Avena nuda L.) grown in hydroponics and in soil culture were investigated under supply with sole NH + 4 -N, sole NO − 3 -N, or a combination. Sole NO − 3 -fed oat plants accumulated more biomass than sole NH + 4 -fed ones. The highest biomass accumulation was observed when N was supplied with both NH + 4 -N and NO − 3 -N. Growth of the plant root increased with the proportion of NO − 3 in the cultural medium. Better root growth and higher root/shoot ratio were consistently observed in NO − 3 -fed plants. However, root vigor was the highest when N was supplied with NO − 3 +NH + 4 . NH + 4 supply reduced the rhizosphere pH but did not affect P uptake by plants grown in soils with CaHPO 4 added as P source. No P deficiency was observed, and plant P concentrations were generally above 2 g kg −1 . P uptake was increased when N was supplied partly or solely as NO − 3 -N, similarly as biomass accumulation. The results suggested that oat was an NO − 3 -preferring plant, and NO − 3 -N was essential for plant growth and the maintenance of root absorption capacity. N supply with NH + 4 -N did not improve P nutrition, which was most likely due to the absence of P deficiency.

Van der Waals heterostructures (vdWHs), obtained by artificially stacking 2D layered material (2DLM) plains upon each other, are brand new structures that have exhibited novel electronic and optoelectronic properties and attracted a great deal of attention. So far, the results are only based on devices with symmetrical configurations: devices predominated by vdWH parts, or cross-like configurations combined with both vdWHs and extra individual 2DLM layers. Quite different gate tunable phenomena have been observed for these two configurations even though 2DLMs with similar band alignments were used, which may be due to the different device configurations utilized. For a deeper understanding, rational investigation on configuration-dependent properties of vdWHs is needed. Here, using MoTe2/MoS2 as an example, vdWH device is artificially designed with two asymmetrical configurations. Through comparing the respective results, it is found that the properties that stem only from the vdWH, i.e., the rectification behavior and open voltage in photovoltaic effect, are independent of the device structures. However, other properties, i.e., drain currents, short circuit currents, and photoreponse performances, strongly depend on the configuration used. These results give a guideline on studying the intrinsic properties of vdWHs and optimizing the device structures for better performances.

Increasing evidences have demonstrated that activation of alternative complement pathway plays an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to investigate the association of complement factor H (CFH), a key regulator of the alternative complement pathway, with the disease activity of AAV. Plasma CFH levels were measured in 82 patients with myeloperoxidase (MPO)-AAV in active stage. Of the 82 patients, plasma CFH levels of 27 patients were longitudinally measured. Serum anti-CFH autoantibodies were screened in AAV patients. Circulating complement activation profiles including C4d, Bb, C3a, C5a and soluble C5b-9 of AAV patients in active stage were further detected. Associations between plasma CFH levels and clinicopathological parameters as well as the prognosis were analyzed. Plasma CFH levels were significantly lower in active AAV patients compared with AAV patients in remission and normal controls. Correlation analysis showed that plasma CFH levels inversely correlated with initial serum creatinine, Birmingham Vasculitis Activity Score (BVAS), proportion of total crescents and cellular crescents in renal specimens, and circulating levels of C3a, C5a and Sc5b-9, meanwhile positively correlated with estimated glomerular filtration rate (eGFR), hemoglobin levels and circulating levels of C3. Moreover, multivariate survival analysis revealed that plasma CFH levels were independently associated with composite outcome of death or end stage renal disease (ESRD) in AAV patients, after adjusting for age, gender, hemoglobin level and urinary protein (P = 0.03, HR 0.85, 95 % CI 0.73–0.98) or adjusting for age, gender, total crescents (%) and urinary protein (P = 0.03, HR 0.85, 95 % CI 0.73–0.98), while not as an independent predictor after adjusting for age, gender, serum creatinine and urinary protein (P = 0.57, HR 0.96, 95 % CI 0.83–1.11). In conclusion, plasma CFH levels are associated with disease activity, and, to some extent, associated with composite outcomes of patients with MPO-ANCA-associated vasculitis.

This study aimed to evaluate the clinical efficacy of different target volumes in pelvic radiotherapy in postoperative treatment of cervical cancer based on the Sedlis criteria.Patients who admitted to our department for post-operative radiotherapy of cervical cancer from December 2001 to December 2011 and met the Sedlis criteria were retrospectively analysed. The incidences of acute and late radiation injuries, and overall, disease-free and tumour-specific survival with reduced-volume pelvic and whole-pelvis radiotherapy were evaluated and compared.A total of 371 patients were included in the study, including 239 receiving whole-pelvis radiotherapy and 132 receiving reduced-volume pelvic radiotherapy. The volume of contours for mean PTV volumes, bilateral femoral heads and small intestine volumes in reduced-volume pelvic radiotherapy were lower than whole-pelvis radiotherapy; the results were similar to the V10, V20, V30, V40 and V45 for pelvic bone marrow and small intestine dose volume (both p0.05). The acute radiation injury observed in the two groups was mainly haematologic toxicity and upper and lower gastrointestinal symptoms. The incidences of acute radiation injury, and late radiation injury of gastrointestinal and urinary tracts were both significantly lower with reduced-volume pelvic radiotherapy than with whole-pelvis radiotherapy (both p0.05). Moreover, there was no significant difference in the incidence of lower extremity oedema, or 2-year or 5-year overall, disease-free or tumour-specific survival between groups (all p0.05).Reduced-volume pelvic radiotherapy could relieve acute and late radiation injuries, especially myelosuppression, and did not affect long-term survival. Advanced in knowledge: Our study shows that reduced-volume base on National Comprehensive Cancer Network 2016 is more fit for cervical cancer than others.

Background The aim of the study was to assess the role of irradiation in the expression of HIF-1α, VEGF, and P53 in human cervical carcinoma cells under a simulated hypoxia environment. Material/Methods The tetrazolium-based colorimetric cellular assay (MTT) and flow cytometry (FCM) were used to detect the growth inhibition rates of HeLa cells in different groups. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to observe gene and protein expression of HIF-1α, VEGF, and P53. The effect of HIF-1α on radioresistance and expression of VEGF and P53 were confirmed with the HIF-1α siRNA in vivo and in vitro. Results Hypoxic conditions enhanced the radiation resistance dependent on HIF-1α by elevating the expression of VEGF and inhibiting the expression of p53. After transfection of HIF-1α siRNA, MTT assay showed the survival rates were increased in the cells receiving irradiation under hypoxia. The expression of VEGF decreased significantly more than that of cells transfected with sense oligodeoxynucleotides, while an opposite result was found in the expression of P53 protein in the same X-ray dose (p

Background After activation, the complement system is involved in the pathogenesis of Immunoglobulin A nephropathy (IgAN). Complement factor H (CFH) is a crucial inhibitory factor of the alternative pathway of the complement system. The study investigated the effects of urinary CFH levels on IgAN progression. Methods A total of 351patients with IgAN participated in this study. They were followed up for an average of 51.8±26.6 months. Renal outcome was defined as a composite endpoint, that included instances of end-stage renal disease (ESRD),≥ 50% decline in estimated glomerular filtration rate (eGFR) or doubling of plasma creatinine levels. Urinary CFH levels were measured by enzyme-linked immunosorbent assay and calculated as the ratio of urinary CFH over creatinine (uCFH/uCr). Results In the whole cohort, uCFH/uCr values were associated with disease progression either as continuous [log(uCFH/uCr)] or categorical traits (dichotomous and quartile variables) after adjusting for eGFR, proteinuria, mean arterial blood pressure, histological grading and immunosuppressive therapy in the Cox proportional hazard model. Kaplan-Meier analysis showed that higher uCFH/uCr values at baseline predicted worse renal outcome during follow-up (log-rank, P

Complement activation is common in patients with IgA nephropathy (IgAN) and associated with disease severity. Our recent genome-wide association study of IgAN identified susceptibility loci on 1q32 containing the complement regulatory protein-encoding genes CFH and CFHR1-5, with rs6677604 in CFH as the top single-nucleotide polymorphism and CFHR3-1 deletion (CFHR3-1∆) as the top signal for copy number variation. In this study, to explore the clinical effects of variation in CFH, CFHR3, and CFHR1 on IgAN susceptibility and progression, we enrolled two populations. Group 1 included 1178 subjects with IgAN and available genome-wide association study data. Group 2 included 365 subjects with IgAN and available clinical follow-up data. In group 1, rs6677604 was associated with mesangial C3 deposition by genotype-phenotype correlation analysis. In group 2, we detected a linkage between the rs6677604-A allele and CFHR3-1∆ and found that the rs6677604-A allele was associated with higher serum levels of CFH and lower levels of the complement activation split product C3a. Furthermore, CFH levels were positively associated with circulating C3 levels and negatively associated with mesangial C3 deposition. Moreover, serum levels of the pathogenic galactose-deficient glycoform of IgA1 were also associated with the degree of mesangial C3 deposition in patients with IgAN. Our findings suggest that genetic variants in CFH, CFHR3, and CFHR1 affect complement activation and thereby, predispose patients to develop IgAN.

In an attempt to find the correlation of aberrant expression of long intergenic noncoding RNAs (lincRNAs) with cancer, twenty-five samples of breast cancer tissue and respective adjacent normal tissue were studied for the expression of lincRNAs by RNA-seq. Among the 538 lincRNAs studied, 124 lincRNAs were exclusively expressed in cancer adjacent tissues and 62 lincRNAs were exclusively expressed in the cancer tissues. Furthermore, the expression of 134 lincRNAs was higher while 272 lower in breast cancer tissue compared with adjacent tissue. The expression of four selected lincRNAs (BC2, BC4, BC5, and BC8) was validated by semi-quantitative and real-time PCR. It was revealed that expression of lincRNA-BC5 was positively correlated with patients' age, pathological stage, and progesterone receptor concentration, while lincRNA-BC8 was negatively correlated with progesterone receptor expression. Higher expression of lincRNA-BC4 was seen in advanced breast cancer grade. LincRNA-BC2 showed no specific changes in the pathological features studied. Interactions between selected lincRNAs and breast cancer associated proteins were highly suggested by RPIseq based on the specific secondary structure. The results demonstrated that this group of lincRNAs was aberrantly expressed in breast cancer. They might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of breast cancer.

The aim of this study was to establish a method of purifying intact complement factor H (CFH) from human plasma. CFH was isolated from human plasma by polyethylene glycol (PEG) precipitation, following three sequential chromatographic columns, which consisted of l-lysine Sepharose column, Resource Q column and Sephacryl S-300 High Resolution HiPrep 16/60 column. All the above steps were performed at 4°C by Fast Protein Liquid Chromatography (FPLC) AKTA Purifier 10 with Frac-900. Identification of the purified CFH was confirmed by SDS-PAGE and Western blot. The following functions of the purified CFH were further analyzed compared with the commercial CFH in vitro: (1) binding ability with C3b; (2) binding ability with mCRP; (3) the protecting function of the hemolysis of sheep red blood cells; (4) the cofactor role for complement factor I-mediated proteolytic inactivation of C3b. Homogeneous CFH was purified from the plasma fraction through the above four steps. The purity and the functions of the purified CFH were comparable to the commercial CFH. The yield of CFH was 26±3% in our study. Compared with previous methods, our method was high yield with high purity. We established a stable and feasible system for purifying intact CFH, which could be used in the lab and clinical investigations.

Recently, many studies have shown that Single immunoglobulin interleukin-1 receptor related protein (SIGIRR), a member of the IL-1R family acting as a negative regulator of TLR/IL-1R signaling, affects autoimmune responses in animal model of systemic lupus erythematosus (SLE). However, the role of SIGIRR in the pathogenesis of human SLE has not been widely explored. In this study, we analyzed the frequency of SIGIRR-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) of SLE patients and its correlation with disease activity as well as the clinical data. Circulating SIGIRR-positive CD4+ T cells were quantified in 51 SLE patients and 38 healthy controls by using flow cytometer. Results showed that the percentages of SIGIRR-positive CD4+ T cells were decreased in the PBMCs of SLE patients compared with healthy controls (Z = −5.49, P