OBJECTIVE: To observe the effects of the "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture on key regulatory factors during mitochondrial apoptosis of testicular tissue in asthenozoospermia mice, and explore the potential mechanism of the protective effect of acupuncture on reproductive function. METHODS: Thirty C57BL/6 male mice were randomly divided into a blank group, a model group and an acupuncture group, 10 mice in each group. In the model and the acupuncture groups, the intraperitoneal injection of cyclophosphamide (30 mg•kg^-1•d^-1) was delivered for 7 days to prepare the asthenozoospermia model. After the success of modeling, the modeled mice in the acupuncture group were intervened with "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture, once daily and the needles were retained for 20 min. The duration of the intervention was 2 weeks. The general condition of each mouse was observed, and the body mass was recorded before modeling, after modeling and after intervention completion. After intervention, the testicular mass was recorded and the weight coefficient was calculated, and the mouse sperm quality was examined; the serum contents of testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were detected using ELISA, the morphology of testicular tissue was observed using HE, the mitochondrial ultra-microstructure of testicular tissue was observed under transmission electrone microscopy, the mitochondrial membrane potential level of testicular tissue was detected using JC-1 staining, the positive rate of apoptosis cell of testicular tissue was observed using TUNEL; and the mRNA and protein expression of b-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome c (Cyt C), apoptotic protease-activating factor1 (Apaf-1), Caspase-9 and Caspase-3 of testicular tissue was detected using real-time quantitative fluorescence PCR and Western blot methods separately; and the positive expression of Cleaved Caspase-3 of the testicular tissue was detected using immunohistochemistry. RESULTS: Compared with the blank group, the mice were in listless spirits, had shaggy hairs, the reduced appetite and movement, and weight loss in the model group (P<0.01); the testicular mass and the weight coefficient decreased (P<0.01); the total number of sperms, sperm motility, and sperm viability were declined (P<0.01); while the levels of serum T, FSH, and LH were dropped (P<0.01). The morphology of seminiferous tubules in testicular tissue was abnormal, the number of spermatogenic cells and the number of mitochondria decreased, the inner mitochondrial crest was fractured and lost, and vacuoles appeared. The level of mitochondrial membrane potential was reduced (P<0.01); and the positive rate of apoptosis cell in testicular tissue increased (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was elevated (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 was dropped (P<0.01), and the average absorbance value of Cleaved Caspase-3 increased (P<0.01). When compared with the model group, in the acupuncture group, the general condition of mice was improved, the testicular mass and the weight coefficient elevated (P<0.01); the total number of sperms, sperm motility, and sperm viability increased (P<0.01); while the levels of serum T, FSH, and LH rose (P<0.01). The pathological morphology of testicular tissue and the inner mitochondrial ultra-microstructure were ameliorated, the level of mitochondrial membrane potential was elevated (P<0.01); the positive rate of apoptosis cell was reduced (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was dropped (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 elevated (P<0.05), and the average absorbance value of Cleaved Caspase-3 declined (P<0.01). CONCLUSION "Zhibian" (BL54)-toward- "Shuidao" (ST28) acupuncture may ameliorate mouse reproductive function by inhibiting mitochondrial apoptosis pathway, alleviating testicular tissue damage in the asthenospermia mice induced by cyclophosphamide.
Animals ; Male ; Mice ; Apoptosis ; Acupuncture Therapy ; Mitochondria/metabolism* ; Asthenozoospermia/genetics* ; Humans ; Testis/metabolism* ; Mice, Inbred C57BL ; Spermatozoa/metabolism* ; Acupuncture Points ; Sperm Motility ; Testosterone/blood* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Caspase 3/genetics* ; Follicle Stimulating Hormone/blood* ; Reproduction ; Cytochromes c/genetics* ; bcl-2-Associated X Protein/genetics* ; Apoptotic Protease-Activating Factor 1/genetics*

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Objective To investigate the ameliorative effect of salidroside on diabetes retinopathy (DR) rats and its mechanism. Methods Male SD rats were randomly divided into blank group, model group, low-dose and high-dose salidroside treatment groups. Except for the blank group, other groups were modeled by intraperitoneal injection of streptozotocin. After successful modeling, treatment groups were injected intraperitoneally with [50 mg/(kg.d)] and [100 mg/(kg.d)] salidroside respectively, for 4 weeks; the blank group and model group were injected with corresponding doses of saline. ELISA was used to measure the expression levels of antioxidant-related enzyme activity and inflammatory factors in blood glucose and serum of rats in each group. Retinal tissue lesions were detected by HE staining, and the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) in retinal tissues were detected by immunohistochemical staining. Western blot analysis was used to detect the expression of phosphatidylinositol 3 kinase (PI3K) , nuclear factor κB p65 (NF-κB p65), phosphorylated p38 MAPK (p-p38 MAPK), and phosphorylated protein kinase B (p-AKT) proteins. Results Compared with model group, salidroside could significantly reduce blood glucose level and increase body mass in DR rats. The serum levels of superoxide dismutase (SOD) and catalase (CAT) were significantly increased, while the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and IL-1β were reduced. The protein expression of VEGF, ICAM-1, NF-κB p65 and p-p38 MAPK was significantly decreased, while the protein expression of PI3K and p-AKT was increased. Conclusion Salidroside can reduce DR in rats by inhibiting oxidative stress and immune inflammatory response, which may be related to the reduction of abnormal expression of VEGF and ICAM-1 and the activation of PI3K/AKT signaling pathway.
Animals ; Male ; Rats ; Blood Glucose ; Diabetes Mellitus ; Inflammation/metabolism* ; Intercellular Adhesion Molecule-1/metabolism* ; NF-kappa B/metabolism* ; Oxidative Stress ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Retinal Diseases ; Tumor Necrosis Factor-alpha/metabolism* ; Vascular Endothelial Growth Factor A/metabolism*

OBJECTIVES: Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke. Previous studies revealed that delayed recanalization might cause serious ischemia/reperfusion injury. However, plenty of evidences showed delayed recanalization improved neurological outcomes in acute ischemic stroke. This study aims to explore the role of delayed recanalization on blood-brain barrier (BBB) in the penumbra (surrounding ischemic core) and neurological outcomes after middle cerebral artery occlusion (MCAO). METHODS: Recanalization was performed on the 3rd day after MCAO. BBB disruption was tested by Western blotting, Evans blue dye, and immunofluorescence staining. Infarct volume and neurological outcomes were evaluated on the 7th day after MCAO. The expression of fibroblast growth factor 21 (FGF21), fibroblast growth factor receptor 1 (FGFR1), phosphatidylinositol-3-kinase (PI3K), and serine/threonine kinase (Akt) in the penumbra were observed by immunofluorescence staining and/or Western blotting. RESULTS: The extraversion of Evans blue, IgG, and albumin increased surrounding ischemic core after MCAO, but significantly decreased after recanalization. The expression of Claudin-5, Occludin, and zona occludens 1 (ZO-1) decreased surrounding ischemic core after MCAO, but significantly increased after recanalization. Infarct volume reduced and neurological outcomes improved following recanalization (on the 7th day after MCAO). The expressions of Claudin-5, Occludin, and ZO-1 decreased surrounding ischemic core following MCAO, which were up-regulated corresponding to the increases of FGF21, p-FGFR1, PI3K, and p-Akt after recanalization. Intra-cerebroventricular injection of FGFR1 inhibitor SU5402 down-regulated the expression of PI3K, p-Akt, Occludin, Claudin-5, and ZO-1 in the penumbra, which weakened the beneficial effects of recanalization on neurological outcomes after MCAO. CONCLUSIONS Delayed recanalization on the 3rd day after MCAO increases endogenous FGF21 in the penumbra and activates FGFR1/PI3K/Akt pathway, which attenuates BBB disruption in the penumbra and improves neurobehavior in MCAO rats.
Animals ; Rats ; Blood-Brain Barrier/metabolism* ; Brain Ischemia ; Claudin-5/metabolism* ; Infarction, Middle Cerebral Artery/metabolism* ; Ischemic Stroke/metabolism* ; Occludin/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Reperfusion Injury/metabolism*

Objective: To study the effect of gastrodin on oxidative stress and bone tissue around implants in type 2 diabetes mellitus rats (T2DM), so as to provide therapeutic basis for the problems of poor osseointegration and long repair period of implants in type 2 diabetic patients, to provide the basis for the development of new therapeutic drugs. Methods: Forty SD rats aged 5 weeks were divided into control group (n=10) and model group (n=30). The model group was fed with high glycolipid diet for 4 weeks and injected with 35 mg/kg streptozocin. The T2DM were divided into diabetic group (n=10) and gastrodin group (n=10). Pure screw titanium implants were placed in the metaphysis of both tibia. Rats in gastrodin group were given gastrodin 13.6 mg/kg everyday, while the control group and diabetic group were given the same dose of saline solution. Blood glucose was measured every two weeks after operation in all rats. After 4 and 8 weeks, the contents of serum malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to analyze the oxidative stress level in rats. The expression of anti-apoptosis protein [B cell lymphoma/lewkmia-2 (bcl-2)]and apoptosis protein [bcl-2-associated X protein (bax)] was analyzed by immunohistochemistry. HE staining and micro-CT scanning were used to analyze the osseointegration around the implants. Results: The blood glucose of gastrodin [(12.98±2.53), (13.64±1.96), (14.58±3.40) and (12.84±2.82) mmol/L] were significantly lower than that of diabetic group [(20.97±2.27), (17.94±3.76), (23.66±2.90) and (21.22±2.67) mmol/L] at corresponding time point (P<0.017). Four and 8 weeks following surgery, the MDA concentration in gastrodin group [(5.21±1.60) and (3.47±1.17) nmol/ml] was significantly lower than that in diabetic group [(11.42±5.11) and (7.31±1.37) nmol/ml] at the corresponding time points (P<0.017), while SOD activity in gastrodin group [(42.89±6.00) and (53.12±9.73) U/ml] was significantly higher than those in diabetic group [(27.09±6.11) and (32.08±2.97) U/ml] at the corresponding time points (P<0.017). Immunohistochemistry showed that the bcl-2 expression in gastrodin group was significantly higher than that in diabetic group at 4 and 8 weeks following surgery (P<0.017), while the bax expression in gastrodin group was significantly lower than that in diabetic group (P<0.017). Four weeks after surgery, the bone volume/tissue volume (BV/TV), connection density (Conn.D), trabecular number (Tb.N), trabecular thickness (Tb.Th) in gastrodin group were significantly higher than those in diabetic group (P<0.017). There was no significant difference in trabecular separation/spacing (Tb.sp) between gastrodin group and diabetic group (P<0.017). Eight weeks after surgery, the BV/TV, Tb.N in gastrodin group were significantly higher than those in the diabetic group (P<0.017). There was no significant difference in Conn.D between gastrodin group and diabetic group (P<0.017). There was no significant difference in Tb.Th and Tb.sp in three groups (P<0.017). The trabecular structure in gastrodin group was better than that in diabetic group by HE staining. Conclusions: Gastrodin can decrease blood glucose, improve oxidative stress, protect bone tissue from apoptosis and promote bone formation around implants in T2DM.
Animals ; Benzyl Alcohols ; Blood Glucose ; Dental Implants ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2 ; Glucosides ; Proto-Oncogene Proteins c-bcl-2 ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; Tibia ; bcl-2-Associated X Protein

OBJECTIVE: To examine the antiplatelet and antithrombotic activity of Rumex acetosella extract. METHODS: Standard light aggregometry was used for platelet aggregation, intracellular calcium mobilization assessed using Fura-2/AM, granule secretion (ATP release) by luminometer, and fibrinogen binding to integrin α_IIbβ₃ detected using flow cytometry. Western blotting is carried out to determine the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt signaling. RESULTS: Rumex acetosella displayed the ability to inhibit platelet aggregation, calcium mobilization, granule secretion, and fibrinogen binding to integrin α_IIbβ₃. Rumex acetosella has also down-regulated MAPK and PI3K/Akt phosphorylation (all P<0.01). CONCLUSION Rumex acetosella extract exhibits antiplatelet activity via modulating GPVI signaling, and it may protect against the development of platelet-related cardiovascular diseases.
Blood Platelets/metabolism* ; Calcium/metabolism* ; Fibrinogen/metabolism* ; Mitogen-Activated Protein Kinases/metabolism* ; Phosphatidylinositol 3-Kinase/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Phosphorylation ; Plant Extracts/pharmacology* ; Platelet Aggregation ; Platelet Aggregation Inhibitors/pharmacology* ; Platelet Glycoprotein GPIIb-IIIa Complex/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rumex/metabolism*

In this study,mouse models of benign prostatic hyperplasia induced by subcutaneous injection of testosterone propionate was used to investigate the therapeutic effect and mechanism of Urtica hyperborean( UW) extracts on prostate hyperplasia in mice. The effects of UW extracts on prostate index,serum epidermal growth factor( EGF) and dihydrotestosterone( DHT) in model mice were observed,and the EGF and anti-apoptotic factor( Bcl-2) mRNA expression levels were detected as well as pathological changes in prostate tissue. The results showed that the ethyl acetate extraction and alcohol soluble fraction of the UW could significantly reduce the prostate index,reduce the serum DHT and EGF levels( P<0. 01),and significantly decrease the EGF and Bcl-2 mRNA expression( P<0. 01),significantly improved the morphological structure of prostate tissue. The above results confirmed that ethyl acetate extract and alcohol-soluble parts of UW have a good preventive effect on mice prostatic hyperplasia model,and its mechanism may be to reduce androgen levels by regulating polypeptide growth factors and/or inhibiting cell hyperproliferation and promoting apoptosis. This study laid the foundation for the further research on UW.
Animals ; Dihydrotestosterone ; blood ; Epidermal Growth Factor ; blood ; Male ; Medicine, Tibetan Traditional ; Mice ; Plant Extracts ; pharmacology ; Prostatic Hyperplasia ; chemically induced ; drug therapy ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Testosterone Propionate ; Urticaceae ; chemistry

OBJECTIVE: To investigate the anti-apoptotic effect of Angelica polysaccharide (APS) on cryopreservated platelets and its mechanism. METHODS: The platelets were divided into 4 group: control group(4 ℃ stored platelets),APS group (APS-treated platelets stored at 4 ℃), LY294002 group (LY294002-treated platelets stored at 4 ℃) and LY294002+APS group(LY294002+APS treated platelets stored at 4 ℃ ). The expression of platelet membrane glycoprotein CD41 and CD61, as well as the platelet apoptotic rate, Caspase 3 expression and mitochondrial membrane potential (MMP) were detected by flow cytometry; the anti-apoptotic mechanism of APS by PI3K /AKT signaling pathway was analyzed by Western blot assay. RESULTS: The apoptosis rate of platelets in LY294002 group obviously increased, the activity of CD41 and CD61 expression gradually decreased along with the enhancement of LY294002 concentrations (r=-0.953)； compared with control group, the apoptosis rate of platelets in LY294002 group was enhanced significantly(P<0.05)，while the apoptosis rate of platelets in LY294002+APS group significantly was reduced(P<0.05) as compare with LY294002 group, which suggest that APS has an anti-apoptotic effect on the cryopreserved platelets. APS decreased the expression of Caspase-3 and inhibited the reduction of mitochondrial membrane potential induced by LY294002, moreover, APS could increase the activation of PI3K /AKT pathway in Plt. CONCLUSION APS has an anti-apoptotic effect on the cryopreserved platelets through activating the PI3K /AKT pathway, decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.
Angelica ; Apoptosis ; Blood Platelets ; Chromones ; Morpholines ; Phosphatidylinositol 3-Kinases ; Polysaccharides ; Proto-Oncogene Proteins c-akt

Objective To investigate the effects of simvastatin on diabetic neuropathic pain and systematic inflammation in diabetic rats and explore their molecular mechanisms.Methods Totally 24 rats were equally randomized into the normal+vehicle(NV)group,diabetic+vehicle(DV)group,and diabetic+simvastatin(DS)group using the random number table.Streptozotocin(STZ)was used to establish the rat models of diabetes.Blood glucose,body mass,paw withdrawal mechanical threshold(PWMT),and paw withdrawal thermal latency(PWTL)in each group were observed on days 7,14,21,and 28 after STZ injection.On day 28 after STZ injection,rats were sacrificed,and the lumbar spinal dorsal horn and serum were collected.Western blotting was used to detect the expression of receptor for advanced glycation end products(RAGE)and the phosphorylation levels of protein kinase B(AKT),extracellular signal-regulated kinase(ERK),p38,and c-Jun N-terminal kinase(JNK)in the spinal dorsal horn of rats in each group.Enzyme-linked immunosorbent assay was performed to determine the serum concentrations of oxidized low density lipoprotein(ox-LDL)and interleukin-1β(IL-1β).Results On days 14,21 and 28 after STZ injection,the PWMT in DV group were(8.6 ± 0.8),(7.1 ± 1.6),and(7.8 ± 0.8)g respectively,which were significantly lower than (12.0 ± 0.9)(=8.482, =0.000),(11.6 ± 1.5)(=11.309, =0.000),and(11.7 ± 1.5)g(=9.801, =0.000)in NV group.The PWMT in DS group on days 21 and 28 were(9.4 ± 1.4)(=5.780, =0.000)and(9.7 ± 0.9)g(=4.775, =0.003),respectively,which were significantly improved comparing with those of DV group.On days 7,14,21,and 28,there were no significant differences in PWTL among these three groups (all <0.05).The expression of RAGE in the spinal dorsal horn of DV group was significantly higher than those of NV group(=6.299, =0.000)and DS group(=2.891, =0.025).The phosphorylation level of AKT in the spinal dorsal horn of DV group was significantly higher than those of NV group(=8.915,=0.000)and DS group(=4.103,=0.003).The phosphorylation levels of ERK( =8.313,=0.000),p38( =2.965, =0.022),and JNK(=7.459, =0.000)in the spinal dorsal horn of DV group were significantly higher than those of NV group;the phosphorylation level of JNK in the spinal dorsal horn of DS group was significant lower than that of DV group(=3.866, =0.004);however,there were no significant differences in the phosphorylation levels of ERK(=1.987,=0.122)and p38(=1.260,=0.375)in the spinal dorsal horn between DS group and DV group.The serum concentrations of ox-LDL and IL-1β in DV group were(41.86 ± 13.40)ng/ml and(108.16 ± 25.88)pg/ml,respectively,which were significantly higher than those in NV group [(24.66 ± 7.87)ng/ml(=3.606,=0.003)and(49.32 ± 28.35)pg/ml(=5.079,=0.000)] and DS group [(18.81 ± 5.62)ng/ml (=4.833, =0.000)and(32.73 ± 11.73)pg/ml(=6.510, =0.000)].Conclusions Simvastatin can relieve the mechanical allodynia of diabetic rats possibly by inhibiting the activation of RAGE/AKT and the phosphorylation of JNK in the spinal dorsal horn.Simvastatin can also decrease the serum concentrations of ox-LDL and IL-1β in diabetic rats,which may contribute to the relief of systematic inflammation.
Animals ; Diabetes Mellitus, Experimental ; complications ; Hyperalgesia ; Inflammation ; drug therapy ; Interleukin-1beta ; blood ; Lipoproteins, LDL ; blood ; Neuralgia ; drug therapy ; Proto-Oncogene Proteins c-akt ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor for Advanced Glycation End Products ; metabolism ; Simvastatin ; pharmacology

OBJECTIVE: To explore the value of serum microRNA-494 (miR-494) expression in predicting the prognosis of acute renal injury (AKI) after cardiac surgery in children. METHODS: 116 children with AKI after cardiopulmonary bypass for congenital heart disease admitted to Sanya People's Hospital from January 2016 to March 2019 were enrolled. The expression of miR-494 in serum was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and the levels of serum neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were detected by enzyme linked immunosorbent assay (ELISA) of all the children. The children were divided into survival group and death group according to 28-day survival. Serum levels of miR-494, NGAL and KIM-1 were measured in two groups. Multivariate Logistic regression was used to analyze the risk factors of death in children with AKI after cardiac surgery. The receiver operating characteristic (ROC) curve analysis of serum levels of miR-494, NGAL and KIM-1 in predicting prognosis of children with AKI after cardiac surgery was performed. Pearson correlation analysis was used to analyze the correlation between serum levels of miR-494 and NGAL, KIM-1. RESULTS: After cardiopulmonary bypass in 116 children with AKI, 27 cases died and 89 cases survived during the 28-day observation. Compared with the survival group, the proportion of cyanosis in the death group was significantly increased, the proportion of blood perfusion was significantly decreased, the time of cardiopulmonary bypass and postoperative mechanical ventilation were significantly prolonged, and the blood glucose level was significantly increased after operation. There was no significant difference in other general data. The serum levels of miR-494, NGAL and KIM-1 in the death group were significantly higher than those in the survival group [miR-494 (2^-ΔΔCt): 3.75±1.28 vs. 1.48±0.71, NGAL (mg/L): 583.60±52.72 vs. 320.52±31.84, KIM-1 (g/L): 30.53±6.38 vs. 17.40±3.72, all P < 0.01]. Multivariate Logistic regression analysis showed cyanosis [odds ratio (OR) = 1.716, 95% confidence interval (95%CI) was 1.184-2.982, P = 0.039], postoperative blood glucose (OR = 1.925, 95%CI was 1.262-3.387, P = 0.005), serum miR-494 (OR = 2.527, 95%CI was 1.706-5.148, P < 0.001), NGAL (OR = 2.473, 95%CI was 1.620-4.935, P < 0.001) and KIM-1 (OR = 1.805, 95%CI was 1.213-3.106, P < 0.001) were independent risk factors for death in children with AKI after cardiac surgery. ROC curve analysis showed the area under the curve (AUC) to predict the death of children with postoperative AKI was 0.868, 0.857 and 0.819 respectively, AUC of serum miR-494, NGAL and KIM-1 levels combination to predict the death of children with postoperative AKI was the largest (0.964, 95%CI was 0.908-0.997), with a high sensitivity and specificity of 97.0% and 91.8%. The correlation analysis showed the expression level of serum miR-494 was positively correlated with NGAL and KIM-1 in the death group (r₁ = 0.902, r₂ = 0.873, both P < 0.01). CONCLUSIONS Serum levels of miR-494 increased significantly in children with AKI after cardiac surgery, which is an independent risk factor for death in children with AKI after cardiac surgery, and the combination of NGAL and KIM-1 levels had a high value in predicting the prognosis of children with AKI after cardiac surgery.
Acute Kidney Injury/diagnosis* ; Acute-Phase Proteins ; Biomarkers ; Cardiac Surgical Procedures ; Child ; Humans ; Lipocalin-2 ; MicroRNAs/blood* ; Predictive Value of Tests ; Prognosis ; Proto-Oncogene Proteins