Modified Hu-lu-ba-wan protects diabetic glomerular podocytes via promoting PKM2-mediated mitochondrial dynamic homeostasis.

BACKGROUND: Mitochondrial dysfunction is implicated in the progression of diabetic kidney disease (DKD). Damaged mitochondria produce excessive reactive oxygen species (ROS) that can cause apoptosis. Mitochondrial dynamics control the quality and function of mitochondria. Targeting mitochondrial dynamics may reduce ROS-induced apoptosis and improve renal injury in DKD. Modified Hu-lu-ba-wan (MHLBW) shows distinct clinical effects on DKD patients, which are related to its role in antioxidant stress modulation. However, the relevant mechanisms of MHLBW have not been clearly explored. PURPOSE: This study was aimed to evaluate the therapeutic effects of MHLBW on spontaneous DKD mice and clarify the potential mechanisms. METHODS: The main components of MHLBW were identified by HPLC. Using db/db mice as DKD models, we evaluated the therapeutic effects of MHLBW on mice after an 8-week administration. We investigated the molecular mechanism of MHLBW in regulating mitochondrial dynamic homeostasis, podocyte apoptosis, and glomerular damage. After that, computational docking analysis and in vitro experiments were conducted for further mechanism verification. RESULTS: Intragastric administration of MHLBW for 8 weeks in db/db mice significantly improved glucose metabolism, basement membrane thickening, mesangial expansion, glomerular fibrosis, and podocyte injury. MHLBW can reverse podocyte apoptosis via promoting mitochondrial dynamic homeostasis, which was related to regulating the PKM2/ PGC-1α/Opa1 pathway. Berberine (BBR), one of the components of MHLBW, exhibited preeminent affinity with PKM2 as reflected by computational docking analysis. In cultured podocytes, BBR can also prevent apoptosis by promoting PKM2-mediated mitochondrial dynamic homeostasis. CONCLUSION: Our study demonstrates that MHLBW can treat DKD by inhibiting glomerular damage and podocyte apoptosis through positive regulation of PKM2-mediated mitochondrial dynamic homeostasis. These results may provide a potential strategy against DKD.

Developing a RiskS-core Model based on Angiogenesis-related lncRNAs for Colon Adenocarcinoma Prognostic Prediction.

AIM: We screened key angiogenesis-related lncRNAs based on colon adenocarcinoma (COAD) to construct a RiskS-core model for predicting COAD prognosis and help reveal the pathogenesis of the COAD as well as optimize clinical treatment. BACKGROUND: Regulatory roles of lncRNAs in tumor progression and prognosis have been confirmed, but few studies have probed into the role of angiogenesis-related lncRNAs in COAD. OBJECTIVE: To identify key angiogenesis-related lncRNAs and build a RiskS-core model to predict the survival probability of COAD patients and help optimize clinical treatment. METHODS: Sample data were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The HALLMARK pathway score in the samples was calculated using the single sample gene set enrichment analysis (ssGSEA) method. LncRNAs associated with angiogenesis were filtered by an integrated pipeline algorithm. LncRNA-based subtypes were classified by ConsensusClusterPlus and then compared with other established subtypes. A RiskS-core model was created based on univariate Cox, least absolute shrinkage and selection operator (LASSO) regression and stepwise regression analysis. The Kaplan-Meier curve was drawn by applying R package survival. The time-dependent ROC curves were drawn by the timeROC package. Finally, immunotherapy benefits and drug sensitivity were analyzed using tumor immune dysfunction and exclusion (TIDE) software and pRRophetic package. RESULTS: Pathway analysis showed that the angiogenesis pathway was a risk factor affecting the prognosis of COAD patients. A total of 66 lncRNAs associated with angiogenesis were screened, and three molecular subtypes (S1, S2, S3) were obtained. The prognosis of S1 and S2 was better than that of S3. Compared with the existing subtypes, the S3 subtype was significantly different from the other two subtypes. Immunoassay showed that immune cell scores of the S2 subtype were lower than those of the S1 and S3 subtypes, which also had the highest TIDE scores. We recruited 8 key lncRNAs to develop a RiskS-core model. The high RiskS-core group with inferior survival and higher TIDE scores was predicted to benefit limitedly from immunotherapy, but it may be more sensitive to chemotherapeutics. A nomogram designed by RiskS-core signature and other clinicopathological characteristics shed light on rational predictive power for COAD treatment. CONCLUSION: We constructed a RiskS-core model based on angiogenesis-related lncRNAs, which could serve as potential prognostic predictors for COAD patients and may offer clues for the intervention of anti-angiogenic application. Our results may help evaluate the prognosis of COAD and provide better treatment strategies.

Trigonelline inhibits tubular epithelial-mesenchymal transformation in diabetic kidney disease via targeting Smad7.

OBJECTIVES: Diabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes. Inhibiting the epithelial-mesenchymal transition (EMT) of proximal tubule epithelial cells (PTCs) can slow down renal fibrosis. Trigonelline (TRL), an alkaloid isolated from the fenugreek, has demonstrated therapeutic effects on diabetes and its complications. Nevertheless, the underlying mechanisms for the effects of TRL are still obscure. The present study was aimed to evaluate the treatment of TRL against DKD and explore the potential mechanisms. METHODS: The db/db mice were used as a spontaneous model of DKD and TRL solution was administered by daily gavage for 8 weeks. Indicators associated with glucose metabolism, renal function and urinary albumin were tested. Renal fibrosis in diabetic mice was evaluated by histopathological staining. Kidney transcriptomics was performed after confirming therapeutic effects of TRL on DKD mice. Molecular biology techniques and in vitro experiments were utilized for final mechanism verification. RESULTS: Biochemical tests revealed that TRL ameliorated renal damage and reduced microalbuminuria in DKD mice. TRL exhibited a protective effect on PTCs, effectively mitigating tubular EMT and renal fibrosis in diabetic kidneys. Transcriptomics analysis indicated that TRL may target Smad7, an inhibitor of TGF-ß1 signaling, to alleviate fibrosis. Furthermore, in vitro experiments validated that silencing Smad7 abolished the therapeutic effect of TRL. CONCLUSION: Our findings indicate that TRL can alleviate tubular epithelial-mesenchymal transition and renal fibrosis in db/db mice by upregulating Smad7 in PTCs, suggesting that TRL is a promising medicine against DKD.

Multi-target regulation of intestinal microbiota by berberine to improve type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) and its complications are major public health problems that seriously affect the quality of human life. The modification of intestinal microbiota has been widely recognized for the management of diabetes. The relationship between T2DM, intestinal microbiota, and active ingredient berberine (BBR) in intestinal microbiota was reviewed in this paper. First of all, the richness and functional changes of intestinal microbiota disrupt the intestinal environment through the destruction of the intestinal barrier and fermentation/degradation of pathogenic/protective metabolites, targeting the liver, pancreas, visceral adipose tissue (VAT), etc., to affect intestinal health, blood glucose, and lipids, insulin resistance and inflammation. Then, we focus on BBR, which protects the composition of intestinal microbiota, the changes of intestinal metabolites, and immune regulation disorder of the intestinal environment as the therapeutic mechanism as well as its current clinical trials. Further research can analyze the mechanism network of BBR to exert its therapeutic effect according to its multi-target compound action, to provide a theoretical basis for the use of different phytochemical components alone or in combination to prevent and treat T2DM or other metabolic diseases by regulating intestinal microbiota.

PHLDA1 knockdown inhibits inflammation and oxidative stress by regulating JNK/ERK pathway, and plays a protective role in sepsis-induced acute kidney injury.

BACKGROUND: Acute kidney injury (AKI), a prevalent complication of sepsis, causes substantial burden on patients' families as well as the society. More reliable markers are urgently required for the prevention and treatment of AKI. Pleckstrin homology-like domain, family A, member 1 (PHLDA1) was implicated in various diseases, but its involvement in sepsis-induced AKI remains to be explored. The JNK/ERK pathway has been revealed as being involved in progression of sepsis. One previous study demonstrated that PHLDA1 could activate the JNK/ERK pathway in hepatic ischemia/reperfusion injury. Nevertheless, involvement of PHLDA1 in sepsis-triggered AKI through the JNK/ERK pathway has not been probed. METHODS: A cecal ligation and punctured (CLP) mice model of sepsis-induced AKI was established. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence staining were applied to evaluate the expression of PHLDA1. Concentration of blood urea nitrogen (BUN) and serum creatinine (Scr), inflammation markers, including interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α, as well as oxidative stress-associated proteins (catalase, malondialdehyde, superoxide dismutase, and glutathione), in the kidney tissues of mice were evaluated by enzyme-linked-immunosorbent serologic assay. Western blot analysis was applied for measuring protein expression levels. RESULTS: The BUN and SCr levels in mice were obviously elevated in the CLP group compared to the sham group. Moreover, the expression of PHLDA1 was also elevated in the CLP group in comparison to the sham group. Down-regulation of PHLDA1 alleviated renal injury, inflammation, and oxidative stress in AKI model. Mechanistic study showed that PHLDA1 knockdown suppressed the activation of c-JUN N-terminal kinase/p38 and extracellular signal-regulated kinase (JNK/ERK) pathway. CONCLUSION: Down-regulation of PHLDA1 suppressed inflammation and oxidative stress through the modulation of JNK/ERK pathway in sepsis-induced AKI. The results could offer a novel insight into the treatment of patients with sepsis-induced AKI.

New Therapeutic Horizon of Graves' Hyperthyroidism: Treatment Regimens Based on Immunology and Ingredients From Traditional Chinese Medicine.

Graves' disease is an autoimmune disease characterized by goiter and hyperthyroidism, and 25% patients develop GO. Traditional treatment options, such as antithyroid drugs, radioiodine or thyroidectomy, have remained largely unchanged over the past 70 years. For many patients, there is a high rate of recurrence after antithyroid drugs and lifelong hypothyroidism after ablation and thyroidectomy. The symptoms and quality of life of some patients have not been effectively improved. The clinical demand for new therapeutic regimens, coupled with a deeper understanding of the pathophysiology and immunobiology of Graves' disease, has led to the emergence of several new therapeutic ideas, including biologics, small molecule peptides, immunomodulators and teprotumumab, a specific antibody targeting IGF-1R. Besides, the elements of TCM have attracted more and more interests in modern medicine, because some effective components have been successfully used in the treatment of autoimmune diseases. Based on the pathophysiology and efficacy of clinical management and treatment in Graves' hyperthyroidism, here we review the new strategies under investigation and summarize the effective components of traditional Chinese medicine used for Graves' hyperthyroidism, and explore their mechanisms. These therapies have opened a new window for the treatment of Graves' disease, but the exact mechanism and the research direction still need to be further explored.

Research on sleep status, body mass index, anxiety and depression of college students during the post-pandemic era in Wuhan, China.

OBJECTIVE: Wuhan was the first Chinese city to be lockdown for the coronavirus disease 2019 (COVID-19) outbreak in springtime of 2020. The purpose of this study was to investigate the relationship between sleep status, body mass index, anxiety and depression in college students during the post-pandemic era in the universities of Wuhan, China. METHODS: A total of 1457 college students completed the online surveys from December 25, 2020 to January 16, 2021. Collected data included gender, age, school name, native place, grade, major, body mass index (BMI), the scores of self-assessment lists of sleep (SRSS), Zung self-rating anxiety scale (SAS) and Zung depression self-rating scale (SDS). RESULTS: 1445 valid questionnaires (99.18%) were received. Of all the respondents, the prevalence of insomnia, overweight and obesity, anxiety and depression were 32.73%, 19.45%, 15.43% and 62.91%, respectively. Female students were more likely to have insomnia and anxiety than male students. The rate of insomnia, overweight and obesity in postgraduates were higher than undergraduates. Non-medical students were more likely to be overweight and obese than medical students. In addition, insomnia severity was positively correlated to anxiety severity, and BMI was positively correlated to anxiety or depression severity. There was also a positive correlation between the severity of anxiety and depression. CONCLUSION: During the post-pandemic era, insomnia and depression are common problems among college students in Wuhan, suggesting that we should strengthen the sleep education of college students to improve sleeping disorders and psychosomatic health.

Berberine Alleviates Insulin Resistance and Inflammation via Inhibiting the LTB4-BLT1 Axis.

Background: Chronic low-grade inflammation is recognized as a key pathophysiological mechanism of insulin resistance. Leukotriene B4 (LTB4), a molecule derived from arachidonic acid, is a potent neutrophil chemoattractant. The excessive amount of LTB4 that is combined with its receptor BLT1 can cause chronic low-grade inflammation, aggravating insulin resistance. Berberine (BBR) has been shown to relieve insulin resistance due to its anti-inflammatory properties. However, it is not clear whether BBR could have any effects on the LTB4-BLT1 axis. Methods: Using LTB4 to induce Raw264.7 and HepG2 cells, we investigated the effect of BBR on the LTB4-BLT1 axis in the progression of inflammation and insulin resistance. Results: Upon exposure to LTB4, intracellular insulin resistance and inflammation increased in HepG2 cells, and chemotaxis and inflammation response increased in RAW264.7 cells. Interestingly, pretreatment with BBR partially blocked these changes. Our preliminary data show that BBR might act on BLT1, modulating the LTB4-BLT1 axis to alleviate insulin resistance and inflammation. Conclusions: Our study demonstrated that BBR treatment could reduce intracellular insulin resistance and inflammation of hepatic cells, as well as chemotaxis of macrophages induced by LTB4. BBR might interact with BLT1 and alter the LTB4-BLT1 signaling pathway. This mechanism might be a novel anti-inflammatory and anti-diabetic function of BBR.

Efficacy and safety of rituximab for childhood refractory nephrotic syndrome: A meta-analysis of randomized controlled trials / Eficacia y seguridad de rituximab para el síndrome nefrótico refractario infantil: un meta-análisis de ensayos controlados aleatorios

Background: Idiopathic nephrotic syndrome is the most common glomerular disease in children, but there are still some difficulties in treating childhood steroid-dependent or steroid-resistant nephrotic syndrome (SDNS/SRNS). Rituximab (RTX) might be an effective and safe choice.MethodsStudies were searched from PubMed, Web of Science, Cochrane library and some Chinese databases up to April 2020. Only randomized controlled trials (RCT) were included.ResultsOf 1383 screened articles, 6 RCTs with 334 participants were included. RTX was better than the control group at improving relapse-free rate in the short term [RR (risk ratio) (95% CI (confidence interval)), 1.84(1.41, 2.39)]. As for long-term, RTX did not show significant improvement [RR (95% CI), 4.43(.57, 34.67)]; but in subgroup analysis, RTX was still better than conventional drugs and tacrolimus [RR (95% CI), 9.91(1.95, 50.52) and 1.42(1.15, 1.75), respectively]. And there was a difference between the two groups of prednisolone dose after treatment [MD (mean difference) (95% CI), −.22(−.36, −.09) mg/kg/d)]. However, RTX did not significantly improve serum albumin and creatinine [MD (95% CI), 3.46(−1.40, 8.32)g/L and −3.66(−11.79, 4.48)μmol/L, respectively]. No significant differences between the RTX and the control group were found in total adverse events (AEs) or serious AEs.ConclusionChildhood SDNS/SRNS patients appear to benefit from RTX in relapse-free rate and dose of prednisolone use. Also, RTX did not significantly increase the incidence of AEs. But RTX did not show improvements in biological indicators, more studies are required to explain the effect of RTX. (AU)

Antecedentes: El síndrome nefrótico idiopático es la enfermedad glomerular más común en niños, pero aún existen algunas dificultades para tratar el síndrome nefrótico infantil dependiente de esteroides o resistente a esteroides. El rituximab (RTX) podría ser una opción efectiva y segura.MétodosSe realizaron búsquedas en los estudios de PubMed, Web of Science, Cochrane Library y algunas bases de datos chinas hasta abril de 2020. Sólo se incluyó ensayo controlado aleatorio (ECA).ResultadosDe 1.383 artículos seleccionados, se incluyeron 6 ECA con 334 participantes. RTX fue mejor que el grupo control para mejorar la tasa libre de recaídas a corto plazo [Relación de riesgo (IC95%), 1,84 (1,41, 2,39)]. En cuanto a largo plazo, RTX no mostró una mejora significativa [4,43 (0,57, 34,67)]; pero en el análisis de subgrupos, RTX fue aún mejor que los fármacos convencionales y el tacrolimus [9,91 (1,95, 50,52) y 1,42 (1,15, 1,75), respectivamente]. Se encontró una diferencia entre los dos grupos de dosis de prednisolona después del tratamiento [Diferencia media (IC95%), -0,22 (-0,36, -0,09) mg/kg/d)]. Sin embargo, RTX no mejoró significativamente la albúmina sérica y la creatinina [3,46 (-1,40, 8,32) g/L y -3,66 (-11,79, 4,48) μmol/L, respectivamente]. No se encontraron diferencias significativas entre RTX y el grupo de control en los eventos adversos totales (EA) o los EA graves.ConclusiónLos niños con síndrome nefrótico refractario parecen beneficiarse de RTX en la tasa libre de recaídas y la dosis de uso de prednisolona. Además, RTX no aumentó significativamente la incidencia de EA. Pero RTX no mostró mejoras en los indicadores biológicos, se requieren más estudios para explicar el efecto de RTX. (AU)

The Therapeutic Effect of Aromatherapy on Insomnia: a Meta-Analysis.

BACKGROUND: Insomnia is a more and more common sleep disorder, which affects health and quality of life. Aromatherapy is one of the effective treatments to improve sleep quality. This paper is to comprehensively evaluate the existing research on aromatherapy as a treatment of insomnia to verify its therapeutic effect. RESULTS: 16 studies (19 comparisons) met inclusion and exclusion criteria were used for meta-analysis. The results showed that aromatherapy had a significant effect on improving sleep quality (WMD: -2.52; 95% CI: -3.24 to -1.79). Subgroup analysis showed that different types of patients from different countries can improve their sleep quality through aromatherapy. The inhalation group, rather than the massage group had an obvious therapeutic effect, which may be due to the number of studies using massage included in our analysis is too small. What's more, different intervention duration does not seem to have a significant effect on the efficacy of aromatherapy. CONCLUSION: Aromatherapy has a significant effect on improving sleep quality. It can be used as one of the non-pharmacological treatments for insomnia, and relevant guide should be formulated to facilitate future clinical applications.

Characteristics of Viral Shedding in Respiratory Samples and Specific Antibodies Production in 564 COVID-19 Patients.

Positive nucleic acid (NA) results have been found in recovered and discharged COVID-19 patients, but the proportion is unclear. This study was designed to analyze the recurrent positive rate of NA results after consecutively negative results, and the relationship between the specific antibody production and positive NA rate. According to Strengthening the Reporting of Observational Studies in Epidemiology guidelines, data of inpatients in Sino-French New City Branch of Tongji Hospital between Jan. 28 and Mar. 6, 2020 were collected. A total of 564 COVID-19 patients over 14 years old who received the examinations of NA and antibodies against SARS-CoV-2 were included. Days of viral shedding and specific antibodies were recorded and assessed. Among NA tests in respiratory samples (throat swabs, nasopharyngeal swabs, sputum and flushing fluid in alveoli), the patients with all-negative NA results accounted for 17.20%, those with single-positive results for 46.63%, and those with multiple-positive results for 36.17% respectively. Besides, the recurrent positive NA results after consecutively negative results appeared in 66 patients (11.70%). For multiple-positive patients, median viral shedding duration was 20 days (range: 1 to 57 days). Of the 205 patients who received 2 or more antibody tests, 141 (68.78%) had decreased IgG and IgM concentrations. IgM decreased to normal range in 24 patients, with a median of 44 days from symptom onset. Viral shedding duration was not significantly correlated with gender, age, disease severity, changes in pulmonary imaging, and antibody concentration. It is concluded that antibody level and antibody change had no significant correlation with the positive rate of NA tests and the conversion rate after continuous negative NA tests. In order to reduce the recurrent positive proportion after discharge, 3 or more consecutive negative NA test results with test interval more than 24 h every time are suggested for the discharge or release from quarantine.

Efficacy and safety of rituximab for childhood refractory nephrotic syndrome: A meta-analysis of randomized controlled trials.

BACKGROUND: Idiopathic nephrotic syndrome is the most common glomerular disease in children, but there are still some difficulties in treating childhood steroid-dependent or steroid-resistant nephrotic syndrome (SDNS/SRNS). Rituximab (RTX) might be an effective and safe choice. METHODS: Studies were searched from PubMed, Web of Science, Cochrane library and some Chinese databases up to April 2020. Only randomized controlled trials (RCT) were included. RESULTS: Of 1383 screened articles, 6 RCTs with 334 participants were included. RTX was better than the control group at improving relapse-free rate in the short term [RR (risk ratio) (95% CI (confidence interval)), 1.84(1.41, 2.39)]. As for long-term, RTX did not show significant improvement [RR (95% CI), 4.43(.57, 34.67)]; but in subgroup analysis, RTX was still better than conventional drugs and tacrolimus [RR (95% CI), 9.91(1.95, 50.52) and 1.42(1.15, 1.75), respectively]. And there was a difference between the two groups of prednisolone dose after treatment [MD (mean difference) (95% CI), -.22(-.36, -.09) mg/kg/d)]. However, RTX did not significantly improve serum albumin and creatinine [MD (95% CI), 3.46(-1.40, 8.32)g/L and -3.66(-11.79, 4.48)µmol/L, respectively]. No significant differences between the RTX and the control group were found in total adverse events (AEs) or serious AEs. CONCLUSION: Childhood SDNS/SRNS patients appear to benefit from RTX in relapse-free rate and dose of prednisolone use. Also, RTX did not significantly increase the incidence of AEs. But RTX did not show improvements in biological indicators, more studies are required to explain the effect of RTX.

Effects of aromatherapy on anxiety: A meta-analysis of randomized controlled trials.

SCOPE: The effects of aromatherapy on relieving anxiety were controversial. The purpose of this meta-analysis was to evaluate the effects of aromatherapy on anxiety in patients. METHODS AND RESULTS: We searched randomized controlled trials (RCTs) about aromatherapy on decreasing anxiety on PUBMED, WEB OF SCIENCE (January 1990 to October 2019), COCHRANE LIBRARY, EMBASE (updated to October 2019), and the Chinese databases CNKI, WanFang and CBMD. Twenty-five articles (Thirty-two trials) were included in this meta-analysis. The data of scale scores of Spielberger State-Trait Anxiety Inventory (STAI) were extracted. The pooled results demonstrated that inhalation and massage aromatherapy significantly decreased anxiety levels in different conditions. The weighted mean difference was -5.16 for State Anxiety Inventory (SAI) (95%CI: -5.78, -4.55, p<0.001) and -2.85 for Trait Anxiety Inventory (TAI) (95%CI: -3.95, -1.75, p<0.001). No side effects were mentioned in all of studies. CONCLUSION: The meta-analysis suggested that aromatherapy with different essential oils could alleviate anxiety significantly no matter the reason of anxiety. However, the proper dosage of essential oils needs further research.

Angiopoietin-1 Promotes the Integrity of Neovascularization in the Subcutaneous Matrigel of Type 1 Diabetic Rats.

OBJECTIVE: This study aimed to investigate the effects of Ang-1 on neovascularization of diabetic organs by subcutaneous Matrigel angiogenesis model, established in type 1 diabetic rats. METHODS: Ang-1 adenoviral vector was constructed. The rat model was established by STZ and divided into four group. The Matrigel was inserted subcutaneously into the abdominal cavity of rats at 8 weeks, the treatment group was injected with Ang-1 adenovirus vector via tail vein, and the rats were sacrificed at 10 weeks. Neovascularization of Matrigel was observed with transmission electron microscopy. The marker of vascular endothelial cell and pericyte were detected by immunofluorescence. Immunohistochemical detection of the neovascular endothelial junction protein was performed. RT-PCR was used to determine protein expression of neovascular in Matrigel. RESULTS: Vascular cavity-like structure could be seen in subcutaneous Matrigel of diabetic rats, and the cavity was filled with a lot of red blood cells. Transmission electron microscopy showed that neovascular endothelial structure of the Matrigel was incomplete, while the Ang-1 treatment group had more vascular cavity-like structures, intact vascular endothelial structure, and reduced inflammatory cell infiltration in Matrigel. Additionally, the integrity of vascularization improved, and the marker of pericyte and the cell tight junctions protein was upregulated in Ang-1 treatment group. CONCLUSION: Hyperglycemia could induce pathological angiogenesis in subcutaneous Matrigel of diabetic rats, and Ang-1 could upregulate the expression of intercellular junction protein in subcutaneous Matrigel of diabetic rats and promote the integrity of neovascularization in the subcutaneous Matrigel of diabetic rats.

[Value of acute renal injury associated biomarkers for patients in intensive care unit].

OBJECTIVE: To evaluate the early predictive and diagnostic significance of the acute kidney injury (AKI) associated biomarkers for patients in the intensive care unit (ICU).
 METHODS: From January to June, 2014, relevant clinical data of participants were collected upon admission to the intensive care unit (ICU) in Affiliated Hospital of Zunyi Medical College. Levels of serum cystatin C (sCys C), neutrophil gelatinase-associated lipocalin (sNGAL), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1), interleukin-18 (uIL-18), and N-acetyl-beta-D-glucosaminidase (uNAG) were detected by enzyme linked immune sorbent assay (ELISA), and compared between AKI and non-AKI patients. Diagnostic significance of these biomarkers was evaluated by a receiver operating characteristic (ROC) curve and the area under the ROC curve.
 RESULTS: A total of 176 patients were enrolled in this study. Among them, 71 patients were diagnosed as AKI, in which 57 patients hospitalized with AKI and 14 developed AKI after 24 h hospitalization. The renal replacement therapy ratio was increased with the progress of clinical stage for AKI. AKI mortality rate was 18.8% (46.5% of the total number of deaths). The levels of sCys C, sNGAL, uNGAL, and uIL-18 in AKI patients were increased compared with those in the non-AKI patients (P<0.05). With the progress of AKI, sCys C, and uNGAL levels were also elevated. In 14 patients who suffered from AKI 24 h after hospitalization, the average levels of sCys C, uNGAL, uIL-18, and uKIM-1 were significantly increased (P<0.05). Sensitivity and specificity of the uNGAL, sCys C, and uIL-18 in AKI diagnosis were 97.2%, 76.1%, 54.9% and 93.3 %, 96.2%, 78.1%, respectively. The areas under the ROC curve of uNGAL, sCys C, and uIL-18 were 0.99, 0.90, and 0.69, respectively.
 CONCLUSION: uNGAL, sCys C and uIL-18 can be used to predict and diagnose AKI, and to evaluate the AKI clinical stage.