Evaluation of environmental factors and microbial community structure in an important drinking-water reservoir across seasons.

The composition of microbial communities varies in water and sediments, and changes in environmental factors have major effects on microbiomes. Here, we characterized variations in microbial communities and physicochemical factors at two sites in a large subtropical drinking water reservoir in southern China. The microbiomes of all sites, including the diversity and abundance of microbial species, were determined via metagenomics, and the relationships between microbiomes and physicochemical factors were determined via redundancy analysis. The dominant species in sediment and water samples differed; Dinobryon sp. LO226KS and Dinobryon divergens were dominant in sediment samples, whereas Candidatus Fonsibacter ubiquis and Microcystis elabens were dominant in water. The diversity was also significantly different in microbial alpha diversity between water and sediment habitats (p < 0.01). The trophic level index (TLI) was the major factor affecting the microbial community in water samples; Mycolicibacterium litorale and Mycolicibacterium phlei were significantly positively related to TLI. Furthermore, we also studied the distribution of algal toxin-encoding genes and antibiotic-resistant genes (ARGs) in the reservoir. It found that water samples contained more phycotoxin genes, with the cylindrospermopsin gene cluster most abundant. We found three genera highly related to cylindrospermopsin and explored a new cyanobacteria Aphanocapsa montana that may produce cylindrospermopsin based on the correlation through network analysis. The multidrug resistance gene was the most abundant ARG, while the relationship between ARGs and bacteria in sediment samples was more complicated than in water. The results of this study enhance our understanding of the effects of environmental factors on microbiomes. In conclusion, research on the properties, including profiles of algal toxin-encoding genes and ARGs, and microbial communities can aid water quality monitoring and conservation.

Comparative performance of the GenoLab M and NovaSeq 6000 sequencing platforms for transcriptome and LncRNA analysis.

BACKGROUND: GenoLab M is a recently established next-generation sequencing platform from GeneMind Biosciences. Presently, Illumina sequencers are the globally leading sequencing platform in the next-generation sequencing market. Here, we present the first report to compare the transcriptome and LncRNA sequencing data of the GenoLab M sequencer to NovaSeq 6000 platform in various types of analysis. RESULTS: We tested 16 libraries in three species using various library kits from different companies. We compared the data quality, genes expression, alternatively spliced (AS) events, single nucleotide polymorphism (SNP), and insertions-deletions (InDel) between two sequencing platforms. The data suggested that platforms have comparable sensitivity and accuracy in terms of quantification of gene expression levels with technical compatibility. CONCLUSIONS: Genolab M is a promising next-generation sequencing platform for transcriptomics and LncRNA studies with high performance at low costs.

Breastfeeding restored the gut microbiota in caesarean section infants and lowered the infection risk in early life.

BACKGROUND: The initialization of the neonatal gut microbiota (GM) is affected by diverse factors and is associated with infant development and health outcomes. METHODS: In this study, we collected 207 faecal samples from 41 infants at 6 time points (1, 3, and 7 days and 1, 3, and 6 months after birth). The infants were assigned to four groups according to delivery mode (caesarean section (CS) or vaginal delivery (VD)) and feeding pattern (breastfeeding or formula milk). RESULTS: The meconium bacterial diversity was slightly higher in CS than in VD. Three GM patterns were identified, including Escherichia/Shigella-Streptococcus-dominated, Bifidobacterium-Escherichia/Shigella-dominated and Bifidobacterium-dominated patterns, and they gradually changed over time. In CS infants, Bifidobacterium was less abundant, and the delay in GM establishment could be partially restored by breastfeeding. The frequency of respiratory tract infection and diarrhoea consequently decreased. CONCLUSION: This study fills some gaps in the understanding of the restoration of the GM in CS towards that in VD.

Prediction of ESRD in IgA Nephropathy Patients from an Asian Cohort: A Random Forest Model.

BACKGROUND/AIMS: There is an increasing risk of end-stage renal disease (ESRD) among Asian people with immunoglobulin A nephropathy (IgAN). A computer-aided system for ESRD prediction in Asian IgAN patients has not been well studied. METHODS: We retrospectively reviewed biopsy-proven IgAN patients treated at the Department of Nephrology of the Second Xiangya Hospital from January 2009 to November 2013. Demographic and clinicopathological data were obtained within 1 month of renal biopsy. A random forest (RF) model was employed to predict the ESRD status in IgAN patients. All cases were initially trained and validated, taking advantage of the out-of-bagging(OOB) error. Predictors used in the model were selected according to the Gini impurity index in the RF model and verified by logistic regression analysis. The area under the receiver operating characteristic(ROC) curve (AUC) and F-measure were used to evaluate the RF model. RESULTS: A total of 262 IgAN patients were enrolled in this study with a median follow-up time of 4.66 years. The importance rankings of predictors of ESRD in the RF model were first obtained, indicating some of the most important predictors. Logistic regression also showed that these factors were statistically associated with ESRD status. We first trained an initial RF model using gender, age, hypertension, serum creatinine, 24-hour proteinuria and histological grading suggested by the Clinical Decision Support System for IgAN (CDSS, www.IgAN.net). This 6-predictor model achieved a F-measure of 0.8 and an AUC of 92.57%. By adding Oxford-MEST scores, this model outperformed the initial model with an improved AUC (96.1%) and F-measure (0.823). When C3 staining was incorporated, the AUC was 97.29% and F-measure increased to 0.83. Adding the estimated glomerular filtration rate (eGFR) improved the AUC to 95.45%. We also observed improved performance of the model with additional inputs of blood urea nitrogen (BUN), uric acid, hemoglobin and albumin. CONCLUSION: In addition to the predictors in the CDSS, Oxford-MEST scores, C3 staining and eGFR conveyed additional information for ESRD prediction in Chinese IgAN patients using a RF model.

Serum D-dimer is a potential predictor for thromboembolism complications in patients with renal biopsy.

Renal biopsy has been widely recommended in clinic to determine the histological patterns of kidney disease. To prevent bleeding complications, patients should routinely stop anticoagulants prior to renal biopsy. However, patients with kidney disease are susceptible to thromboembolisms, particularly in those with severe hypoalbuminemia. This study was designed to investigate the application of serum D-dimer as a predictor for thrombotic events after renal biopsy. 400 consecutive native renal biopsies were prospectively included in this 2-month follow-up study. The overall incidence of bleeding and thrombotic complication is 4%, including hematuria or large perinephric hematoma (2.5%, n = 10) and thrombotic complication (1.5%, n = 6). Compared to low serum D-dimer (<2.00 µg/ml), subjects in the group of high serum D-dimer (≥2.00 µg/ml) were more incline to develop thrombotic complications (9.1% versus 0.3%; RR, 30.33; p < 0.001). D-dimer correlated positively with age (rs = 0.258, P < 0.001). Inverse correlations were found for albumin (rs = -0.339, P < 0.001). Taken together, patients with high serum D-dimer carry an increased risk of thrombotic complications after renal biopsy. Our findings suggest that serum D-dimer can serve as a potential predictor for thrombotic events in patients with kidney disease. Further cautions should be given to these subjects.

Glycoprotein non-metastatic melanoma protein b (Gpnmb) is highly expressed in macrophages of acute injured kidney and promotes M2 macrophages polarization.

Acute kidney injury (AKI) is an increasingly common disorder that is strongly linked to short- and long-term morbidity and mortality. During AKI process, macrophages, one of the important immune response cells, can polarize into M1 and M2 subtype from M0 subtype. It is well-known that M1 macrophages play a pro inflammatory role while M2 macrophages play an anti-inflammatory role. Glycoprotein non-metastatic melanoma protein b (Gpnmb) is a glycosylated transmembrane protein highly expressed in numerous cells, including osteoblasts, dendritic cells and macrophages. Gpnmb serves as a negative regulator of inflammation in macrophages and has a protective effect on injuries. In acute kidney injury, the macrophage has been shown diverse roles depending on different phenotype. This study provided gene expression and protein expression evidence that Gpnmb was highly expressed in M2 macrophages in the damaged areas of kidney after ischemia-reperfusion injury. Then, we successful isolated and culture mouse bone marrow-derived macrophages (BMMφ) and found that Gpnmb showed different expression levels in M0, M1 and M2 BMMφ: lowest in M1, highest in M2. After knocking down Gpnmb with si-Gpnmb, BMMφ M2 polarization and secretion of anti-inflammatory cytokines IL-10 and TGF-ß were inhibited, while M1 polarization and secretion of proinflammatory cytokines IL-1ß and TNF-α were promoted. Moreover, IL-4-STAT6 pathway was involved in the promotion of M2 polarization by Gpnmb. Taken together, Gpnmb may serve as a potential biomarker of AKI and play a protective role against the AKI by modulating the polarization of macrophage.

Spontaneous Left Renal Subcapsular Hematoma and Right Hip Hematoma in a Hemodialysis Patient: A Case Report and Review of the Literature.

For maintenance hemodialysis (MHD) patients, the blood is in low hypercoagulable state due to the use of heparin or low molecular weight heparin during dialysis. It is not rare to see hematoma in the puncture site. In recent years, several cases have been reported of spontaneous kidney rupture, but no hip hematoma, let alone both occurred in succession. There was one MHD patient with spontaneous kidney bleeding and hip hematoma in our hospital in 2014, and we provided effective treatment and follow-up.

[A case of light and heavy chain deposition disease].

Monoclonal immunoglobulin deposition disease is rare in medical practice. The light and heavy chain deposition disease is characterized by deposition of monoclonal antibodies in the basement of membrane. Kidney is the most frequently involved organ. There was a male patient diagnosed as light and heavy chain deposition disease in department of Nephrology of the Second Xiangya Hospital, Central South University by renal biopsy. After treatment by oral prednisone, melphalan and thalidomide, the patient's proteinuria and serum creatinine decreased. The retrospective analysis of this case provides a guide for doctors to understand the light and heavy chain deposition disease. Early diagnosis and treatment could improve the prognosis.

Gpnmb/osteoactivin: an indicator and therapeutic target in tumor and nontumorous lesions.

Non-metastatic melanoma glycoprotein B (Gpnmb), a type I transmembrane glycoprotein, was first cloned and described in low-metastatic human melanoma and xenografts in 1995. Up to now a growing number of studies have confirmed that Gpnmb is expressed not only in numerous normal tissues but also at pathological sites and malignant tissues and often connected with the invasive and metastatic phenotypes, including breast cancer. Nowadays, immunotherapeutic approaches for cancer therapy, by which monoclonal antibodies (Mabs) target tumor specific antigens, have shown great potential. Glembatumumabvedotin, also called CR011-vcMMAE, is a Mab-drug conjugate which was developed for the treatment of Gpnmb-expressing cancers. Several phase I/II studies have confirmed the safety and activity of glembatumumabvedotin in patients with advanced/metastatic breast cancer and unresectable cutaneous melanoma. Moreover, increasing numbers of studies have supported the potential roles of targeting Gpnmb with glembatumumabvedotin in patients with recurrent osteosarcoma, uveal melanoma, ALS, Gaucher disease, pancreatic ductal adenocarcinoma etc. This review will summarize the latest understanding of Gpnmb in the aspects of diagnosis, progression and prognosis of pathological disorders and neoplasms, emphasizing the clinical advances in targeting Gpnmb-expressing malignancies.

[Survival analysis and risk factors for arteriovenous fistula in 472 patients].

OBJECTIVE: To evaluate the service life of the arteriovenous fistula (AVF) in patients with dialysis and to explore the associated factors for AVF service life.
 METHODS: A cohort study regarding 472 cases with AVFs at the Second Xiangya Hospital from January 2009 to December 2009 was retrospectively analyzed. The AVF placement-associated primary and secondary failure rates, complications and various risk factors were examined. Kaplan-Meier survival curves and Cox proportional hazard models were used to determine the service life and associated factors.
 RESULTS: By the end of January 1st, 2014, after excluding the patients with indeterminate outcome (72 lost to follow-up; 101 died; 44 transplanted), the primary failure rate was 10.9%, the survival rate for 1, 3 or 5 years was 80.5%, 65.1% or 50.5%. The complication rate and hospitalization rate for AVF were 39.8% and 9.8%, respectively. The influential factors for AVF were diastolic hypotension (HR: 0.86; 95% CI: 0.82 to 0.89), diabetes (HR: 1.87; 95% CI: 1.32 to 3.31) and serum albumin (HR: 0.83; 95% CI: 0.74 to 0.94).
 CONCLUSION: The complications after AVF placement must be considered before the surgery schedule. Hypotension, diabetes and serum albumin are the main risk factors for AVF service life.

Effect of p27 gene combined with Pientzehuang ([characters: see text]) on tumor growth in osteosarcoma-bearing nude mice.

OBJECTIVE: To observe the effect of p27 gene recombinant adenovirus combined with Chinese medicine Pientzehuang ([characters: see text]) on the growth of xenografted human osteosarcoma in nude mice. METHODS: Tissue transplantation was used to construct the orthotopic model of human osteosarcoma Saos-2 cell in nude mice. Thirty tumor-bearing nude mice were randomly divided into 5 groups with 6 mice in each group: blank control group (model of osteosarcoma), empty vector group (recombinant adeno-associated virus-multiple cloning site), Pientzehuang group, p27 gene group and combined treatment group (p27 gene combined with Pientzehuang). The effect of combined treatment on human osteosarcoma was analyzed through the tumor formation, tumor volume and inhibition rate of tumor growth. The expression of p27 was measured by immunohistochemical staining and Western blot. RESULTS: The orthotopic model of osteosarcoma in nude mice was successfully constructed. The general appearance of tumor-bearing nude mice in Pientzehuang and p27 gene groups was markedly improved compared with the blank control group; and in the combined treatment group it was significantly improved compared with the Pientzehuang and p27 gene groups. The tumor growth in the Pientzehuang and p27 gene groups was significantly inhibited compared with the blank control group P<0.05); while in the combined treatment group it was markedly inhibited compared with the Pientzehuang and p27 gene groups (P<0.05). The rates of tumor growth inhibition were 34.1%, 56.5% and 63.8% in the Pientzehuang, p27 gene and combined treatment groups, respectively. Meanwhile, the protein expression of p27 gene in the p27 gene group was significantly increased compared with the blank control group (P<0.05); and it was significantly increased in the combined treatment group compared with the p27 gene and Pientzehuang groups (P<0.05). CONCLUSION: p27 gene introduced by adenovirus combined with Pientzehuang can inhibit the growth of human osteosarcoma cell Saos-2 in nude mice.

Disseminated nocardiosis in a patient with nephrotic syndrome following HIV infection.

In the present study, a case of disseminated abscesses caused by Nocardia in a patient undergoing immunosuppressive therapy for nephrotic syndrome and infected with human immunodeficiency virus (HIV) is described. To the best of our knowledge, this is the first such case to be reported. The patient had membranous nephropathy and received systemic corticosteroid therapy for one year. During this time, the patient was diagnosed with HIV and developed disseminated abscesses in the lungs, brain and hip. Pathogens isolated from sputum and pus were identified as Nocardia asteroides. The patient was successfully treated following surgical drainage of the abscesses and by oral administration of trimethoprim-sulfamethoxazole.

[Research progress of Th17 cells and glomerulonephritis].

T helper (Th) 17 cells are a kind of Th cell subset, and are distinct from the Th1 and Th2 cells and produce interleukin-17A (IL-17A, IL-17). Th17 cells have a mechanism of independent differentiation and developmental regulation. The differentiation and cytokine secretion of Th17 cells are regulated by TGF-ß, IL-6, IL-23 and orphan nuclear receptor (RORγt). IL-17A induces pro-inflammatory cytokines and chemokines, mediating neutrophil recruitment. Increasing evidence implicated involvement of Th17 cells in anti-glomerular basement membrane disease, lupus nephritis and pauciimmune glomerulonephritis. In this review, we discussed the discovery of Th17 subset, its properties, its relationship with other Th subsets and involvement of Th17 cells in glomerulonephritis.

Effects of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in contrast-induced nephropathy.

Contrast-induced nephropathy (CIN) is considered the third leading cause of iatrogenic acute kidney injury in high-risk patients undergoing radiographic procedures. The main mechanism leading to CIN is medullary hypoxia due to decreased renal blood flow, secondary to renal artery vasoconstriction and direct tubular toxicity by contrast medium. Furthermore, experimental data suggests that an activated renin-angiotensin-aldosterone system (RAAS) plays a role in the pathophysiology of CIN. However, the role of RAAS blockers, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in CIN is controversial. They have been reported to be effective in the prevention of CIN in previous studies, but some studies have concluded that they were associated with an increased risk of CIN, especially in patients with pre-existing renal impairment. In summary, there is no solid data to link ACE inhibitors and ARB to CIN, and larger randomised controlled trials are necessary to further investigate their role in the development of CIN. In this review, we discuss the pathophysiology of CIN, the role of RAAS on the development of CIN, and the effect of RAAS blockers on CIN.

Excellent outcome of tubulointerstitial nephritis and uveitis: case report and five-year follow-up.

Acute tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease usually having a good prognosis. But the recurrence of uveitis and the chronic progression of kidney injury are still main problems. We report a 15-year-old girl with TINU who showed proteinuria, pathological renal change, multiple organ dysfunction, and immune disorders. After 2 months of 1 mg/kg/day corticosteroid therapy, 24-h urine protein, liver function tests, and creatine kinase returned to normal level. In spite of this, steroid was tapered off slowly and small dose of steroid maintenance therapy lasted for 1 year. Her kidney and ocular symptoms did not recur during 5 years of follow-up. We suggest low-dose steroid maintenance therapy to decrease the recurrence of the TINU syndrome.

[Metabolic syndrome and chronic kidney disease in a rural adult population of Hunan province, China].

OBJECTIVE: To explore the relationship between metabolic syndrome and chronic kidney disease (CKD) in a rural adult population of Hunan province. METHODS: 1953 residents (older than 18 years) from the same village were randomly selected, using a stratified, multistage sampling method. All residents were interviewed and tested for albuminuria with morning spot urine albumin to creatinine ratio (abnormal: >/= 30 mg/g), reduced renal function with estimated glomerular filtration rate by modified MDRD equation [abnormal: < 60 ml/min (1.73 m(2))]. The associations of kidney damage indicators with demographic characteristics (age, gender, smoking status), indicators on health (diabetes, hypertension) and metabolic syndrome traits were examined. RESULTS: Eligible data of 1709 subjects were enrolled in the study. After the adjustment of age, gender and other metabolic syndrome traits, participants with metabolic syndrome had a higher prevalence of CKD (19.3% vs. 13.2%, P < 0.001) than those without the syndrome. As the number of metabolic syndrome traits increased, so did the prevalence of CKD. There seemed to be a strong and independent association between metabolic syndrome and chronic kidney disease. For participants without hypertension and diabetes, metabolic syndrome was also associated with CKD (OR value 1.733, 95%CI: 1.20 - 2.41, P = 0.004). CONCLUSION: In these 1709 adults under this study from a village of southern China, metabolic syndrome seemed to be associated with CKD.

Norcantharidin ameliorates proteinuria, associated tubulointerstitial inflammation and fibrosis in protein overload nephropathy.

Norcantharidin (NCTD), the demethylated analog of cantharidin isolated from Mylabris, is an anticancer drug routinely used against various human cancers in China. The aims of this study are to learn if NCTD has a protective action against severe proteinuria and consequent interstitial inflammation and fibrosis, and if the inhibition of nuclear factor-kappaB (NF-kappaB) and connective tissue growth factor (CTGF) by NCTD might be involved. Male Sprague-Dawley rats with protein overload nephropathy induced by intraperitoneally injected bovine serum albumin were used as a model. The histopathological examination of kidney tissue in the 9th week by light microscopy and scanning electron microscopy revealed that inflammatory cells had extensively infiltrated into the tubulointerstitial areas with interstitial fibrosis. The administration of NCTD at 0.1 mg/kg/day to the bovine-serum-albumin-injected animal models effectively reduced the proteinuria, and prevented the proteinuria-induced interstitial inflammation and fibrosis. Expressions of the NF-kappaB p65 subunit and CTGF, detected by immunohistochemistry, Western blotting and reverse-transcription polymerase chain reaction, were upregulated in protein overload nephropathy and were attenuated by NCTD. Inhibition of the expressions of the NF-kappaB p65 subunit and CTGF was one beneficial effect of NCTD. These results suggest that in addition to the antiproteinuric action of NCTD, due to its anti-inflammatory and antifibrotic effects as shown in the present study, it may become a therapeutic agent for proteinuria and its associated chronic inflammatory and fibrotic nephropathy.

Comparative cytotoxicity of high-osmolar and low-osmolar contrast media on HKCs in vitro.

BACKGROUND: Radiocontrast-induced nephropathy is a clinically important complication of intravascularly applied radiocontrast media. A predominant toxic effect of contrast media on renal tubules has been shown in previous clinical trials and animal experiments. Bax and Bcl-2 are members of the Bcl-2 family. Caspases are a family of cell death proteases, caspase-3 is one of the key executioners of apoptosis. In this study, we evaluated the cytotoxicity of high-osmolar contrast media (HOCM; diatrizoate) and low-osmolar contrast media (LOCM; iohexol) on human renal tubular epithelial cells (HKCs), and determined the regulatory roles of Bax/Bcl-2 and caspase-3 on apoptosis induced by contrast media (CM) in HKCs. METHODS: An HKC line was used. Experiments were divided into 7 groups: the HOCM group with iodine 111 mg/mL, HOCM group with iodine 74 mg/mL, LOCM group with iodine 111 mg/mL, LOCM group with iodine 74 mg/mL, mannitol high-osmolar control group, mannitol low-osmolar control group and a culture media control group . The cytotoxicity of HOCM and LOCM were evaluated by cell proliferation and viability assay (MTT assay) and lactate dehydrogenase (LDH) release. Apoptosis were assessed by Hochest 33258 fluorescence-stained cytospins, TUNEL staining, DNA agarose gel electrophoresis, electron microscope and flow cytometric DNA analysis. The protein ex-pression of Bax/Bcl-2 was determined by Western blot analysis, and caspase-3 activity was also determined by the fluo-rometric method. RESULTS: Compared with the control group, LDH levels increased significantly (p<0.05) and cell viability decreased in cells treated with HOCM or LOCM (p<0.05) in an osmotic pressure-, iodinated ion- and time-dependent manner; in the HOCM groups, diatrizoate induced cultured HKC apoptosis. In the LOCM groups, iohexol did not induce apoptosis. Compared with equal osmotic pressure mannitol, apoptosis increased in HKCs incubated with diatrizoate (p<0.05). Bax/Bcl-2 production and caspase-3 activity were up-regulated in cultured HKCs treated with HOCM iodine 74 or 111 mg/mL meglumine diatrizoate. CONCLUSIONS: Both HOCM and LOCM had toxic effects on HKCs, HOCM was more cytotoxic than LOCM; HOCM induced cultured HKC apoptosis while LOCM did not induce cultured HKC apoptosis in the indicated concentrations. The regulation of apoptosis induced by HOCM in HKCs may be regulated by Bax/Bcl-2 and caspase-3.