Apelin-13 alleviates contrast-induced acute kidney injury by inhibiting endoplasmic reticulum stress.

Contrast-induced acute kidney injury (CI-AKI) is a severe complication associated with significant morbidity and mortality, and effective therapeutic strategies are still lacking. Apelin is an endogenous physiological regulator with antioxidative, anti-inflammatory and antiapoptotic properties. However, the role of apelin-13 in CI-AKI remains unclear. In our study, we found that the protein expression levels of apelin were significantly downregulated in rat kidney tissues and HK-2 cells during contrast media treatment. Moreover, we explored the protective effect of apelin-13 on renal tubule damage using in vitro and in vivo models of CI-AKI. Exogenous apelin-13 ameliorated endoplasmic reticulum stress, reactive oxygen species and apoptosis protein expression in contrast media-treated cells and rat kidney tissues. Mechanistically, the downregulation of endoplasmic reticulum stress contributed critically to the antiapoptotic effect of apelin-13. Collectively, our findings reveal the inherent mechanisms by which apelin-13 regulates CI-AKI and provide a prospective target for the prevention of CI-AKI.

Is intravenous iodinated contrast medium administration really harmful in hospitalized acute kidney injury patients: a propensity score-matched study.

OBJECTIVES: To evaluate the effects of intravenous iodinated contrast medium (ICM) administration on the deterioration of renal function (DRF), new renal replacement therapy (RRT) induction and mortality of hospitalized acute kidney injury (AKI) patients. METHODS: Adult hospitalized patients undergoing a contrast-enhanced or unenhanced CT scan within 7 days after AKI diagnosis from January 2015 to December 2019 were identified in this retrospective study. Propensity score matching was performed. Outcomes in 7 and 30 days after CT scan were compared between the contrast and non-contrast groups. Additional analyses were also performed in patients stratified by SCr levels at AKI diagnosis, times and time of CT scan, and in patients without chronic kidney disease or RRT requirement prior to CT scan. RESULTS: In total, 1172 pairs were generated after 1:1 propensity score matching from 1336 cases exposed to ICM and 2724 unexposed. No significant differences were found in the outcomes between the two groups: DRF, 7.8% vs 9.0% (odds ratio (OR) 0.83, 95% confidence interval (CI) 0.62-1.11) in 7 days, 5.1% vs 5.4% (OR 0.93, 95%CI 0.64-1.34) in 30 days; new RRT induction, 2.3% vs 3.3% (OR 0.72,95%CI 0.43-1.18) in 7 days, 4.2% vs 4.5% (OR 0.95,95%CI 0.64-1.41) in 30 days; and mortality, 3.9% vs 4.8% (OR 0.83,95%CI 0.56-1.22) in 7 days, 9.0% vs 10.2% (OR 0.88,95%CI 0.68-1.15) in 30 days. Subset analyses showed similar results. CONCLUSION: Intravenous ICM administration during AKI duration did not increase the risks of DRF, new RRT induction, and mortality in 7 and 30 days after CT scan. KEY POINTS: • Intravenous ICM administration in hospitalized AKI patients does not increase the risks of deterioration of renal function, RRT induction, and mortality in 7 and 30 days after CT scan. • The effects of intravenous ICM on adverse outcomes are minimal even in AKI patients with high level of SCr values or multiple CT scans.

Post-contrast acute kidney injury in a hospitalized population: short-, mid-, and long-term outcome and risk factors for adverse events.

OBJECTIVES: To investigate the prognosis including major adverse kidney events within 30 days (MAKE30) and 90-day and 1-year adverse outcome in hospitalized patients with post-contrast acute kidney injury (PC-AKI) to identify high-risk factors. METHODS: This retrospective observational study included 288 PC-AKI patients selected from 277,898 patients admitted to hospitals from January 2015 to December 2015. PC-AKI was defined according to the 2018 guideline of European Society of Urogenital Radiology. Multivariable Cox regression and logistic regression analyses were used to analyze main outcome and risk factors. RESULTS: PC-AKI patients with AKI stage ≥ 2 had much higher incidence of MAKE30 than those with AKI stage 1 (RR = 7.027, 95% CI 4.918-10.039). Persistent renal dysfunction, heart failure, central nervous system failure, baseline eGFR < 60 mL/min/1.73 m2, oliguria or anuria, blood urea nitrogen ≥ 7.14 mmol/L, respiratory failure, and shock were independent risk factors of 90-day or 1-year adverse prognosis (p < 0.05). Compared with transient renal dysfunction, PC-AKI patients with persistent renal dysfunction had a higher all-cause mortality rate (RR = 3.768, 95% CI 1.612-8.810; RR = 4.106, 95% CI 1.765-9.551) as well as combined endpoints of death, chronic kidney disease, or end-stage renal disease (OR = 3.685, 95% CI 1.628-8.340; OR = 5.209, 95% CI 1.730-15.681) within 90 days or 1 year. CONCLUSIONS: PC-AKI is not always a transient, benign creatininopathy, but can result in adverse outcome. AKI stage is independently correlated to MAKE30 and persistent renal dysfunction may exaggerate the risk of long-term adverse events. KEY POINTS: • PC-AKI can result in adverse outcome such as persistent renal dysfunction, dialysis, chronic kidney disease (CKD), end-stage renal disease (ESRD), or death. • AKI stage is independently correlated to MAKE30. • Persistent renal dysfunction may exaggerate the risk of long-term adverse events.

Clinical efficacy of robotic spine surgery: an updated systematic review of 20 randomized controlled trials.

Purpose: To determine whether using robots in spine surgery results in more clinical advantages and fewer adverse consequences. Methods: Between October 1990 and October 2022, a computer-based search was conducted through the databases of PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, China Biology Medicine, VIP databases, and WAN FANG. The study only included randomized controlled trials (RCTs) comparing the clinical efficacy and safety of robot-assisted surgery with those of conventional spine surgery. The review was conducted following PRISMA 2020, and AMSTAR-2 was used to evaluate the methodological quality. R version 4.2.1 was used in the meta-analysis. The Cochrane Collaboration Tool was used for evaluating the risk of bias. Results: This study analyzed 954 participants from 20 RCTs involving cervical spondylosis, lumbar degenerative disease, scoliosis, etc. The robot-assisted group outperformed the freehand group in terms of intraoperative blood loss, number of screws in grade A position, grade A + B position, radiation dose, and hospital stay. Operation duration, visual analog scale scores of low back pain, Oswestry disability index, and radiation exposure time did not significantly differ between the two groups. Conclusions: Although robotic spine surgery is more accurate in pedicle screw placement than conventional methods, the robot group did not demonstrate an advantage in terms of clinical efficacy. Studies of complications and cost-effectiveness are still very rare.

Meta-analysis of the clinical efficacy and safety of oblique lateral interbody fusion and transforaminal interbody fusion in the treatment of degenerative lumbar spondylolisthesis.

Objective: The aim of this study was to comprehensively evaluate the efficacy of oblique lateral interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of degenerative lumbar spondylolisthesis by meta-analysis. Methods: A computer-based search of PubMed, Cochrane Library, Embase, Web of Science Core Collection databases, the China National Knowledge Infrastructure, China Biology Medicine, and Wanfang Digital Periodicals was conducted from the time of inception of each database to December 2021. The review process was conducted according to the PRISMA guidelines and registered in the PROSPERO database. Meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library. Results: Thirteen studies were included in the statistical analysis. One randomized controlled study and 12 cohort studies with 954 patients were included. In terms of operation time, intraoperative blood loss, Oswestry disability index score, intervertebral height, and complications, the OLIF group was better than the TLIF group, and the difference was statistically significant (P < 0.05). There was no significant difference between the two groups in terms of visual analogue scale score, lumbar lordosis or fused segment lordosis (P > 0.05). Conclusion: Both OLIF and TLIF are effective surgical modalities in the treatment of degenerative lumbar spondylolisthesis. They achieve similar therapeutic effects, but OLIF is superior to TLIF in restoring intervertebral height. At the same time, OLIF has the advantages of short operation time and less intraoperative blood loss.

A Bibliometric Analysis and Visualization of Current Research Trends in Chinese Medicine for Osteosarcoma.

BACKGROUND: To illustrate the research framework, overall knowledge structure, and development trends of Chinese medicine (CM) treatment for osteosarcoma (OS) by using a bibliometric analysis and newly developed visualization tools. METHODS: Research datasets were acquired from the Web of Science (WOS) database from January 1, 1980 to September 30, 2019. VOS viewer and Citespace software was used to analyze the data and generate visualization knowledge maps. Annual trends of publications, distribution of institutes, distribution of journals, citation and H-index status, co-authorship status, research hotspots and co-citation status were analyzed. RESULTS: A total of 223 publications in the WOS database met the requirement. The number of published articles showed a rise but the citation frequency and the H-index of China were relatively low. The cooperation between the countries, institutes and authors were relatively weak. Most publications were basic researches. Most of the previous researches focused on basic mechanisms of CM in treating OS, and therapy and improvement of dosage form may become a frontier in this research field. CONCLUSIONS: Compared with other fields, the field of CM treatment for osteosarcome is still in infancy. The distribution of researches is imbalanced and cooperation between countries, institutions and authors remains to be strengthened. Furthermore, basic research occupies an absolute dominant position, and the exploration of the molecular mechanism of CM in preventing and treating OS may become a key point in the future.

Effects of mesenchymal stem cells in renovascular disease of preclinical and clinical studies: a systematic review and meta-analysis.

Renal artery stenosis (RAS) causes severe renovascular hypertension, worsening kidney function, and increased cardiovascular morbidity. According to recent studies, mesenchymal stem cells (MSCs) administration is a promising therapy for the improvement of RAS outcomes. The meta-analysis aims to evaluate the therapeutic effects of MSC therapy on RAS. We performed a search in MEDLINE, Web of Science, Embase, and Cochrane Library from inception to 5, October 2022. We included 16 preclinical and 3 clinical studies in this meta-analysis. In preclinical studies, the pooled results indicated that animals treated with MSCs had lower levels of systolic blood pressure (SBP) (SMD = - 1.019, 95% CI - 1.434 to - 0.604, I2 = 37.2%, P = 0.000), serum creatinine (Scr) (SMD = - 1.112, 95% CI - 1.932 to - 0.293, I2 = 72.0%, P = 0.008), and plasma renin activity (PRA) (SMD = - 0.477, 95% CI - 0.913 to 0.042, I2 = 43.4%, P = 0.032). The studies also revealed increased levels of renal blood flow (RBF) in stenotic kidney (STK) (SMD = 0.774, 95% CI - 0.351 to 1.197, I2 = 0%, P = 0.000) and the glomerular filtration rate (GFR) of STK (SMD = 1.825, 95% CI 0.963 to 2.688, I2 = 72.6%, P = 0.000). In clinical studies, the cortical perfusion and fractional hypoxia of the contralateral kidney (CLK) were alleviated by MSC therapy. Taken together, this meta-analysis revealed that MSCs therapy might be a promising treatment for RAS. However, due to the discrepancy between preclinical studies and early clinical trials outcomes, MSC therapy couldn't be recommended in clinical care for the moment, more high-quality randomized controlled clinical trials are needed to validate our conclusions and standardize MSCs protocols.

Deep learning-based high-accuracy quantitation for lumbar intervertebral disc degeneration from MRI.

To help doctors and patients evaluate lumbar intervertebral disc degeneration (IVDD) accurately and efficiently, we propose a segmentation network and a quantitation method for IVDD from T2MRI. A semantic segmentation network (BianqueNet) composed of three innovative modules achieves high-precision segmentation of IVDD-related regions. A quantitative method is used to calculate the signal intensity and geometric features of IVDD. Manual measurements have excellent agreement with automatic calculations, but the latter have better repeatability and efficiency. We investigate the relationship between IVDD parameters and demographic information (age, gender, position and IVDD grade) in a large population. Considering these parameters present strong correlation with IVDD grade, we establish a quantitative criterion for IVDD. This fully automated quantitation system for IVDD may provide more precise information for clinical practice, clinical trials, and mechanism investigation. It also would increase the number of patients that can be monitored.

Machine learning for early discrimination between transient and persistent acute kidney injury in critically ill patients with sepsis.

Acute kidney injury (AKI) is commonly present in critically ill patients with sepsis. Early prediction of short-term reversibility of AKI is beneficial to risk stratification and clinical treatment decision. The study sought to use machine learning methods to discriminate between transient and persistent sepsis-associated AKI. Septic patients who developed AKI within the first 48 h after ICU admission were identified from the Medical Information Mart for Intensive Care III database. AKI was classified as transient or persistent according to the Acute Disease Quality Initiative workgroup consensus. Five prediction models using logistic regression, random forest, support vector machine, artificial neural network and extreme gradient boosting were constructed, and their performance was evaluated by out-of-sample testing. A simplified risk prediction model was also derived based on logistic regression and features selected by machine learning algorithms. A total of 5984 septic patients with AKI were included, 3805 (63.6%) of whom developed persistent AKI. The artificial neural network and logistic regression models achieved the highest area under the receiver operating characteristic curve (AUC) among the five machine learning models (0.76, 95% confidence interval [CI] 0.74-0.78). The simplified 14-variable model showed adequate discrimination, with the AUC being 0.76 (95% CI 0.73-0.78). At the optimal cutoff of 0.63, the sensitivity and specificity of the simplified model were 63% and 76% respectively. In conclusion, a machine learning-based simplified prediction model including routine clinical variables could be used to differentiate between transient and persistent AKI in critically ill septic patients. An easy-to-use risk calculator can promote its widespread application in daily clinical practice.

Thoracic full-endoscopic unilateral laminotomy with bilateral decompression for treating ossification of the ligamentum flavum with myelopathy.

BACKGROUND: The aim of the present study was to evaluate the curative effect and safety of thoracic full-endoscopic unilateral laminotomy with bilateral decompression (TE-ULBD) for treating ossification of the ligamentum flavum (OLF) with myelopathy. METHODS: Between January 2015 and December 2018, 23 consecutive patients with symptomatic thoracic OLF were treated with TE-ULBD. Of these, 21 (13 women and 8 men, aged 49-75 years) were included in the study and followed up for a minimum of 1 year. The mean blood loss was 15.48 mL (10-30 mL), operative duration was 78.86 min (55-115 min), and hospitalization was 5.05 days (3-15 days). The Japanese Orthopaedic Association (JOA) was used to evaluate spinal cord function, and the curative effect was defined by the JOA improvement rate. The area of OLF (AOLF), the maximum spinal cord compression (MSCC), and the area of spinal cord (ASC) were used to evaluate OLF clearance and spinal cord decompression status. RESULTS: At the final follow up,the JOA score was 8.33 points (5-11 points), which was a significant improvement from the preoperative 5.33 points (3-9 points, P<0.01). The excellent and good rate was 76.19% (16/21). The average preoperative AOLF and AOLF ratio were 85.27±23.66 mm2 and 57.86%±11.86%, respectively, and the postoperative AOLF and AOLF ratio were 16.27±11.75 mm2 and 8.13%±5.38%, respectively. The MSCC increased from 27.99%±13.51% preoperatively to 48.02%±6.66% postoperatively. The ASC was 42.90±10.60 mm2 preoperatively and 64.54±21.36 mm2 postoperatively. There were statistically significant differences in all parameters preoperatively and postoperatively (P<0.01). One case had postoperative hematoma, and the symptoms gradually eased after 3 weeks of conservative treatment. There were no other complications. No recurrence of OLF was detected during the follow-up period. CONCLUSIONS: TE-ULBD is safe and effective for thoracic OLF with the advantages of reduced trauma and bleeding, and faster recovery.

Acute kidney disease in hospitalized acute kidney injury patients.

BACKGROUND: Acute kidney injury (AKI) and chronic kidney disease (CKD) have become worldwide public health problems, but little information is known about the epidemiology of acute kidney disease (AKD)-a state in between AKI and CKD. We aimed to explore the incidence and outcomes of hospitalized patients with AKD after AKI, and investigate the prognostic value of AKD in predicting 30-day and one-year adverse outcomes. METHODS: A total of 2,556 hospitalized AKI patients were identified from three tertiary hospitals in China in 2015 and followed up for one year.AKD and AKD stage were defined according to the consensus report of the Acute Disease Quality Initiative 16 workgroup. Multivariable regression analyses adjusted for confounding variables were used to examine the association of AKD with adverse outcomes. RESULTS: AKD occurred in 45.4% (1161/2556) of all AKI patients, 14.5% (141/971) of AKI stage 1 patients, 44.6% (308/691) of AKI stage 2 patients and 79.6% (712/894) of AKI stage 3 patients. AKD stage 1 conferred a greater risk of Major Adverse Kidney Events within 30 days (MAKE30) (odds ratio [OR], 2.36; 95% confidence interval 95% CI [1.66-3.36]) than AKD stage 0 but the association only maintained in AKI stage 3 when patients were stratified by AKI stage. However, compared with AKD stage 0, AKD stage 2-3 was associated with higher risks of both MAKE30 and one-year chronic dialysis and mortality independent of the effects of AKI stage with OR being 31.35 (95% CI [23.42-41.98]) and 2.68 (95% CI [2.07-3.48]) respectively. The association between AKD stage and adverse outcomes in 30 days and one year was not significantly changed in critically ill and non-critically ill AKI patients. The results indicated that AKD is common among hospitalized AKI patients. AKD stage 2-3 provides additional information in predicting 30-day and one-year adverse outcomes over AKI stage. Enhanced follow-up of renal function of these patients may be warranted.

Development of mortality prediction model in the elderly hospitalized AKI patients.

Acute kidney injury (AKI) correlates with increased health-care costs and poor outcomes in older adults. However, there is no good scoring system to predict mortality within 30-day, 1-year after AKI in older adults. We performed a retrospective analysis screening data of 53,944 hospitalized elderly patients (age > 65 years) from multi-centers in China. 944 patients with AKI (acute kidney disease) were included and followed up for 1 year. Multivariable regression analysis was used for developing scoring models in the test group (a randomly 70% of all the patients). The established models have been verified in the validation group (a randomly 30% of all the patients). Model 1 that consisted of the risk factors for death within 30 days after AKI had accurate discrimination (The area under the receiver operating characteristic curves, AUROC: 0.90 (95% CI 0.875-0.932)) in the test group, and performed well in the validation groups (AUROC: 0.907 (95% CI 0.865-0.949)). The scoring formula of all-cause death within 1 year (model 2) is a seven-variable model including AKI type, solid tumor, renal replacement therapy, acute myocardial infarction, mechanical ventilation, the number of organ failures, and proteinuria. The area under the receiver operating characteristic (AUROC) curves of model 2 was > 0.80 both in the test and validation groups. Our newly established risk models can well predict the risk of all-cause death in older hospitalized AKI patients within 30 days or 1 year.

Role of Nrf2 in Lipopolysaccharide-Induced Acute Kidney Injury: Protection by Human Umbilical Cord Blood Mononuclear Cells.

BACKGROUND: Acute kidney injury (AKI) is one of the common complications of sepsis. Heretofore, there is no effective treatment for septic AKI. Recent studies have revealed that besides treating hematological malignancies, human umbilical cord blood mononuclear cells (hUCBMNCs) show good therapeutic effects on other diseases. But whether hUCBMNCs can protect against septic AKI and its underlying mechanism are unknown. METHODS: The rat model of lipopolysaccharide- (LPS-) induced AKI was developed, and the injection of hUCBMNCs was executed to prevent and treat AKI. ML385, a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor, was used to silence Nrf2. The cell experiments were conducted to elaborate the protective mechanism of Nrf2 pathway. RESULTS: An effective model of LPS-induced AKI was established. Compared to the rats only with LPS injection, the levels of inflammation, reactive oxygen species (ROS), and apoptosis in renal tissues after hUCBMNC injection were markedly attenuated. Pathological examination also indicated significant remission of renal tissue injury in the LPS+MNCs group, compared to rats in the LPS group. Transmission electron microscopy (TEM) showed that the damage of the mitochondria in the LPS+MNCs group was lighter than that in the LPS group. Noteworthily, the renal Nrf2/HO-1 pathway was activated and autophagy was enhanced after hUCBMNC injection. ML385 could partly reverse the renoprotective effect of hUCBMNCs, which could demonstrate that Nrf2 participated in the protection of hUCBMNCs. Cell experiments showed that increasing the expression level of Nrf2 could alleviate LPS-induced cell injury by increasing the autophagy level and decreasing the injury of the mitochondria in HK-2 cells. CONCLUSION: All results suggest that hUCBMNCs can protect against LPS-induced AKI via the Nrf2 pathway. Activating Nrf2 can upregulate autophagy to protect LPS-induced cell injury.

Stanniocalcin-1 Alleviates Contrast-Induced Acute Kidney Injury by Regulating Mitochondrial Quality Control via the Nrf2 Pathway.

Contrast-induced acute kidney injury (CI-AKI) is the third common cause of acute kidney injury (AKI), which is associated with poor short- and long-term outcomes. Currently, effective therapy strategy for CI-AKI remains lacking. Stanniocalcin-1 (STC1) is a conserved glycoprotein with antiapoptosis and anti-inflammatory functions, but the role of STC1 in controlling CI-AKI is unknown. Here, we demonstrated a protective role of STC1 in contrast-induced injury in cultured renal tubular epithelial cells and CI-AKI rat models. Recombinant human STC1 (rhSTC1) regulated mitochondrial quality control, thus suppressing contrast-induced mitochondrial damage, oxidative stress, inflammatory response, and apoptotic injury. Mechanistically, activation of the Nrf2 signaling pathway contributes critically to the renoprotective effect of STC1. Together, this study demonstrates a novel role of STC1 in preventing CI-AKI and reveals Nrf2 as a molecular target of STC1. Therefore, this study provides a promising preventive target for the treatment of CI-AKI.

Novel risk models to predict acute kidney disease and its outcomes in a Chinese hospitalized population with acute kidney injury.

Acute kidney disease (AKD) is a state between acute kidney injury (AKI) and chronic kidney disease (CKD), but the prognosis of AKD is unclear and there are no risk-prediction tools to identify high-risk patients. 2,556 AKI patients were selected from 277,898 inpatients of three affiliated hospitals of Central South University from January 2015 to December 2015. The primary point was whether AKI patients developed AKD. The endpoint was death or end stage renal disease (ESRD) 90 days after AKI diagnosis. Multivariable Cox regression was used for 90-day mortality and two prediction models were established by using multivariable logistic regression. Our study found that the incidence of AKD was 53.17% (1,359/2,556), while the mortality rate and incidence of ESRD in AKD cohort was 19.13% (260/1,359) and 3.02% (41/1,359), respectively. Furthermore, adjusted hazard ratio of mortality for AKD versus no AKD was 1.980 (95% CI 1.427-2.747). In scoring model 1, age, gender, hepatorenal syndromes, organic kidney diseases, oliguria or anuria, respiratory failure, blood urea nitrogen (BUN) and acute kidney injury stage were independently associated with AKI progression into AKD. In addition, oliguria or anuria, respiratory failure, shock, central nervous system failure, malignancy, RDW-CV ≥ 13.7% were independent risk factors for death or ESRD in AKD patients in scoring model 2 (goodness-of fit, P1 = 0.930, P2 = 0.105; AUROC1 = 0.879 (95% CI 0.862-0.896), AUROC2 = 0.845 (95% CI 0.813-0.877), respectively). Thus, our study demonstrated AKD was independently associated with increased 90-day mortality in hospitalized AKI patients. A new prediction model system was able to predict AKD following AKI and 90-day prognosis of AKD patients to identify high-risk patients.

Human umbilical cord blood mononuclear cells protect against renal tubulointerstitial fibrosis in cisplatin-treated rats.

Currently, there is no effective method to prevent renal interstitial fibrosis after acute kidney injury (AKI). In this study, we established and screened a new renal interstitial fibrosis rat model after cisplatin-induced AKI. Our results indicated that rats injected with 4 mg/kg cisplatin once a week for two weeks after firstly administrated with 6.5 mg/kg loading dose of cisplatin could set up a more accurate model reflecting AKI progression to renal interstitial fibrosis. Then, we investigated the effects and possible mechanisms of human umbilical cord blood mononuclear cells (hUCBMNCs) on renal tubular interstitial fibrosis after cisplatin-induced AKI. In rats injected with hUCBMNCs for four times, level of matrix metalloproteinase 7 (MMP-7) in serum and urine, urinary albumin/creatinine ratio, tubular pathological scores, the relative collagen area of the tubulointerstitial region, endoplasmic reticulum dilation and the mitochondrial ultrastructural damage were significantly improved. The level of reactive oxygen species, α-smooth muscle actin (α-SMA), [NOD]-like pyrin domain containing protein 3 and cleaved-Caspase 3 in renal tissue decreased significantly. However, in rats injected with hUCBMNCs for two times, no significant difference was discovered in MMP-7 levels and urinary albumin/creatinine ratio. Although expression of α-SMA and the percentage areas of collagen staining in tubulointerstitial tissues were ameliorated in rats injected with hUCBMNCs for two times, the effects were significantly weaker than those in rats injected with hUCBMNCs for four times. Taken together, our study constructed a highly efficient, duplicable novel rat model of renal fibrosis after cisplatin-induced AKI. Multiple injections of hUCBMNCs may prevent renal interstitial fibrosis after cisplatin-induced AKI.

Human umbilical cord blood mononuclear cells protect against renal tubulointerstitial fibrosis in cisplatin-treated rats.

Currently, there is no effective method to prevent renal interstitial fibrosis after acute kidney injury (AKI). In this study, we established and screened a new renal interstitial fibrosis rat model after cisplatin-induced AKI. Our results indicated that rats injected with 4 mg/kg cisplatin once a week for two weeks after firstly administrated with 6.5 mg/kg loading dose of cisplatin could set up a more accurate model reflecting AKI progression to renal interstitial fibrosis. Then, we investigated the effects and possible mechanisms of human umbilical cord blood mononuclear cells (hUCBMNCs) on renal tubular interstitial fibrosis after cisplatin-induced AKI. In rats injected with hUCBMNCs for four times, level of matrix metalloproteinase 7(MMP-7)in serum and urine, urinary albumin/creatinine ratio, tubular pathological scores, the relative collagen area of the tubulointerstitial region, endoplasmic reticulum dilation and the mitochondrial ultrastructural damage were significantly improved. The level of reactive oxygen species, α-smooth muscle actin (α-SMA), [NOD]-like pyrin domain containing protein 3 and cleaved-Caspase 3 in renal tissue decreased significantly. However, in rats injected with hUCBMNCs for two times, no significant difference was discovered in MMP-7 levels and urinary albumin/creatinine ratio. Although expression of α-SMA and the percentage areas of collagen staining in tubulointerstitial tissues were ameliorated in rats injected with hUCBMNCs for two times, the effects were significantly weaker than those in rats injected with hUCBMNCs for four times. Taken together, our study constructed a highly efficient, duplicable novel rat model of renal fibrosis after cisplatin-induced AKI. Multiple injections of hUCBMNCs may prevent renal interstitial fibrosis after cisplatin-induced AKI.

First 3D 3d-4f interpenetrating structure: synthesis, reaction, and characterization of {[LnCr(IDA)2(C2O4)]}n.

The hydrothermal reaction of Cr(NO3)3, Ln2O3, and iminodiacetate acid (H(2)IDA) in the molar ratio of 1:1:3 produced {[LnCr(IDA)2(C2O4)]}n (Ln = Eu, 1; Sm, 2), which represent the first 3D 3d-4f interpenetrating coordination polymers. In the reaction, the H(2)IDA ligands partly decompose into oxalate anions (ox), which connect Ln(III) ions to form 1D {Ln(ox)}n chains. Each of the Cr(III) ions is tridentate-coordinated by two IDA ligands, which act as tetradentate metalloligands to link {Ln(ox)}n chains to form 3D open networks. The two open networks interpenetrate each other to form nonporous products. 1 and 2 are thermally stable up to 327 and 360 degrees C, respectively. Both of complexes show normally paramagnetic behavior. The luminescent results imply that the energy transfers from Ln(III) to Cr(III) are strong.