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Objective:To investigate the effect of hemorrhagic transformation (HT) and its different subtypes on the clinical outcome of patients with acute ischemic stroke (AIS).Methods:Patients with AIS within 24 h of onset treated in Henan Provincial People's Hospital from January 2018 to January 2021 were retrospectively enrolled. HT was defined as intracranial hemorrhage found by CT reexamination within 7 d after the onset of AIS, and further divided into hemorrhagic infarction (HI) and parenchymal hematoma (PH) according to the classification standard of European Cooperative Acute Stroke Study (ECASS)-Ⅱ. The modified Rankin Scale was used to evaluate the outcome at 90 d after onset. 0-2 was defined as good outcome and 3-5 were defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent influencing factors of the outcomes. Results:A total of 822 patients were enrolled, including 478 males (58.2%), aged 60.6±10.6 years. The median score of the baseline National Institutes of Health Stroke Scale (NIHSS) was 8 (interquartile range: 6-12). Two hundred and eighty-two patients (34.4%) developed HT and 447 (54.4%) had poor outcomes. Multivariate logistic regression analysis showed that PH-1 (odds ratio [ OR] 2.461, 95% confidence interval [ CI] 1.285-4.712; P=0.007), PH-2 ( OR 5.291, 95% CI 1.178-23.758; P=0.030), blood glucose at admission ( OR 1.063, 95% CI 1.018-1.109; P=0.005) and baseline NIHSS score ( OR 1.124, 95% CI 1.076-1.175; P<0.001) were the independent influencing factors of the poor outcomes. Conclusion:Different HT subtypes have different effects on the outcomes of patients with AIS, among which PH-1 and PH-2 are the independent risk factors for poor outcomes.
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Objective:To investigate the monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) for the predictive value of early neurological deterioration (END) and poor outcome in patients with acute anterior circulation ischemic stroke (AACIS).Methods:Patients with AACIS admitted to Henan Provincial People's Hospital from January 2021 to January 2022 were included retrospectively. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score within 7 d of onset increase ≥2 compred with baseline or the increase of motor function score ≥1. The patients were divided into END group and non-END group according to the presence or absence of END. The patients were also divided into good outcome group (0-2 points) and poor outcome group (3-6 points) according to the modified Rankin Scale score 3 months after onset. Multivariate logistic regression analysis was used to determine the independent risk factors for END and poor outcome, and the predictive value of MHR for END and poor outcome was evaluated by receiver operating characteristic (ROC) curve. Results:A total of 522 patients were enrolled, including 338 male (64.8%), aged 61.99±11.39 years old. One hundred and five patients (20.1%) had END, 123 (23.6%) had poor outcome. Multivariate logistic regression analysis showed that baseline NIHSS score (odds ratio [ OR] 1.075, 95% confidence interval [ CI] 1.017-1.137; P=0.010) and MHR (with the lowest quartile as the reference, the third quartile: OR 2.778, 95% CI 1.255-6.151, P=0.012; the fourth quartile: OR 12.645, 95% CI 5.942-26.912; P<0.001) were the independent risk factors for END; the baseline NIHSS score ( OR 1.075, 95% CI 1.021-1.132; P=0.006), END ( OR 2.306, 95% CI 1.010-6.261; P=0.047) and MHR (with the first quartile as reference, the fourth quartile: OR 2.769, 95% CI 1.167-6.569; P=0.021) were the independent risk factors for poor outcomes. ROC curve analysis showed that area under the curve of MHR for predicting END and poor outcome in patients with AACIS were 0.805 (95% CI 0.750-0.860; P<0.001) and 0.747 (95% CI 0.690-0.803; P<0.001) respectively. The best cutoff value was 0.435, the sensitivity was 73.3% and 64.2%, and the specificity was 79.6% and 78.7% respectively. The area under the curve of MHR for predicting END and poor outcome was higher than that of monocyte and HDL-C alone. Conclusion:MHR can be used as a predictor of END and poor outcome in patients with AACIS, and its predictive value is higher than that of monocytes or HDL-C.
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Objective:To explore the expression of microRNA-4695-5p in the serum of colorectal cancer patients and its effect on the proliferation and invasion of colorectal cancer CACO-2 cells.Methods:A total of 43 serum samples of colorectal cancer patients who were admitted to the Department of Gastrointestinal Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University from March 2018 to November 2021 were selected, and serum samples of 43 healthy people who underwent outpatient physical examination were used as controls. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels in the serum of colorectal cancer patients and those of healthy individuals. The miR-4695-5p overexpression plasmid or the negative control plasmid were transfected into CACO-2 cells, namely the miR-4695-5p group and the control group, and the transfection efficiency was verified by qRT-PCR. CCK8 method and Transwell experiment were used to detect the effect of overexpression of miR-4695-5p on the proliferation and invasion of CACO-2 cells. The dual luciferase reporter gene experiment was used to verify the targeted binding relationship between miR-4695-5p and Ras-related C3 botulinum toxin substrate 1 (RAC1). qRT-PCR and Western blot were used to detect the effect of overexpression of miR-4695-5p on the expression of RAC1 gene and Wnt/β-Catenin signaling pathway protein.The software of SPSS28.0 was used to conduct data analysis. The measurement data of normal distribution were espressed by Mean±SD. The t-test was used to compare the means between two groups, and the one-way analysis of variance was used to compare the means of multiple groups. Results:The expression level of miR-4695-5p in the serum of patients with colorectal cancer was significantly lower than that of healthy individuals ( P<0.01). The relative expression levels of miR-4695-5p in the control group and miR-4695-5p group were 1.09 ± 0.65 and 8.83±2.03, respectively. The expression level of miR-4695-5p in CACO-2 cells in the miR-4695-5p group was 8.10 times that of the control group, and CACO-2 cells overexpressing miR-4695-5p were successfully constructed ( P<0.01). Compared with the control group, the proliferation ability of CACO-2 cells in the miR-4695-5p group was significantly reduced ( P<0.05), and the invasion ability of CACO-2 cells was significantly reduced ( P<0.01). Bioinformatics tools and dual luciferase reporter gene experiments confirmed that miR-4695-5p can target and bind RAC1 ( P<0.01). Compared with the control group, the expression of RAC1 gene in the miR-4695-5p group was significantly decreased ( P<0.01), and the expression of Wnt/β-Catenin signaling pathway proteins Wnt3a, β-catenin, and c-MYC decreased significantly. Conclusions:miR-4695-5p is lowly expressed in the serum of colorectal cancer patients. miR-4695-5p inhibits the proliferation and invasion of colorectal cancer CACO-2 cells by targeting the inhibition of RAC1 gene expression and down-regulating the activity of the Wnt/β-Catenin signaling pathway.
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Objective To evaluate the effect of lovastatin on shedding of heparan sulfate proteoglycan (HSPG) and syndecan-1 (SDC-1) in the lung tissues of rats with sepsis-induced acute lung injury.Methods One-hundred and twenty male Wistar rats aged 8-12 weeks,weighing 325-425 g,were randomly divided into 3 groups (n =40 each) using a random number table:sham operation group (group S),cecal ligation and puncture (CLP) group and lovastatin group (group L).Lovastatin 4 mg/kg was injected once a day for 5 consecutive days in S and L groups,while the equal volume of 0.5％ CMC (the solvent) was given in CLP group.Sepsis was produced by CLP on 5th day of administration in CLP and L groups.The left lung was lavaged at 24 h after operation.The broncho-alveolar lavage fluid (BALF) was collected for determination of protein concentrations,white blood cell (WBC) count and percentage of neutrophils.Blood samples were collected for determination of the concentrations of HSPG and SDC-1 in serum (by ELISA).Evans blue was injected at 24 h after operation in the remaining 20 rats of each group.The lungs were removed for examination of the pathological changes and for measurement of HSPG and SDC-1 mRNA and protein expression (using Western blot and PCR),and Evans blue content (reflecting pulmonary capillary permeability) in the lung tissue.Results Compared with group S,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly increased,and HSPG and SDC-1 mRNA and protein expression was down-regulated in CLP and L groups.Compared with group CLP,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly decreased,and HSPG and SDC-1 mRNA and protein expression was up-regulated in group L.The pathological changes of lungs were significantly attenuated in group L as compared with group CLP.Conclusion The mechanism by which lovastatin attenuates acute lung injury induced by sepsis may be related to reduced shedding of HSPG and SDC-1 in lung tissues and improved function of pulmonary vascular endothelium in rats.
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Objective To observe the protective effects of lovastatin against lung injury and the expression changes of adiponectin in the septic rats.Methods Fifty four male Wistar rats weighting 250-300g were randomly divided into the three groups:sham operation group ( group Sham) ,sepsis group ( group CLP) and lovastatin interven tion group (group LOV).Rats were injected with lovastatin (4mg/kg) or 0.5%CMC (vehicle) for five days and then subjected to CLP.At 4h,12h and 24h after operation.BALF was collected to determine the levels of TNF-αand IL-6,lung tissue was obtained to observe histopathological changes,and to detect the content of MPO and MDA,the blood sample was obtained to detect the level of adiponectin.Results In the group Sham,at 4h,12h and 24h time points,the levels of TNF-αwere (1.80 ±0.13)pg/mL,(2.04 ±0.15)pg/mL and (1.930.19)pg/mL;the levels of IL-6 were (20.56 ±0.23)pg/mL,(18.35 ±0.15) pg/mL and (21.23 ±0.20) pg/mL;the contents of MPO were (2.82 ±0.14) U/g tissue,(2.88 ±0.07) U/g tissue and (2.76 ±0.18) U/g tissue;and the levels of MDA were (3.32 ±0.12)nmol/mg,(3.09 ±0.11)nmol/mg and (3.21 ±0.08)nmol/mg;the concentrations of adiponectin were (2.68 ±0.14)μg/mL,(2.80 ±0.07)μg/mL and (2.86 ±0.18)μg/mL.Compared with group Sham,both LOV group and CLP group had increased pulmonary damage:(1)the levels of TNF-α[4h,12h and 24h were (4.23 ± 0.18)pg/mL,(5.62 ±0.24)pg/mL and (5.14 ±0.10)pg/mL,t=28.41,30.98 and 36.62]and IL-6[4h,12h and 24h were (39.12 ±0.17) pg/mL,(47.25 ±0.21) pg/mL and (44.690.27) pg/mL,t =158.90,273.40 and 127.28] of the CLP group in BALF were both increased,and MPO[4h,12h and 24h were (4.85 ±0.13) U/g tissue, (6.17 ±0.08)U/g tissue and (7.84 ±0.10)U/g tissue,t=26.39,79.40 and 60.43]and MDA[4h,12h and 24h were (6.24 ±0.06)nmol/mg,(7.56 ±0.15)nmol/mg and (8.43 ±0.10)nmol/mg,t=53.31,58.86 and 90.06] concentrations in lung homogenate were raised with the decreased expression of serum adiponectin[4h,12h and 24h were (1.35 ±0.10)μg/mL,(1.17 ±0.07)μg/mL and (1.24 ±0.11)μg/mL,t=19.86,12.75 and 18.81](all P<0.05);(2) meanwhile the levels of TNF-α[4h,12h and 24h were (2.85 ±0.17) pg/mL,(3.720.13) pg/mL and (3.240.09)pg/mL,t=12.02、20.73 and 16.68]and IL-6[4h,12h and 24h were (30.75 ±0.22)pg/mL, (37.52 ±0.29)pg/mL and (32.43 ±0.26)pg/mL,t=78.42,68.29 and 83.67]in BALF of the LOV group were all increased,the contents of MPO[4h,12h and 24h were(3.59 ±0.05)U/g tissue,(4.67 ±0.11)U/g tissue and (5.33 ± 0.05)U/g tissue,t=12.03,33.63 and 33.70]and MDA[4h,12h and 24h were (4.45 ±0.10)nmol/mg,(5.01 ± 0.11)nmol/mg and (5.83 ±0.04) nmol/mg,t =17.72,30.23 and 71.75] were also increased with the serum adiponectin concentrations[4h,12h and 24h were (2.09 ±0.08)μg/mL,(2.07 ±0.05)μg/mL and (2.03 ± 0.10)μg/mL,t=8.96,20.79 and 6.30]dicreased(all P<0.05).There were less histopathological changes in the LOV group,and the levels of TNF-α(t=13.46,17.05 and 15.43),IL-6(t=73.70,64.10 and 80.12),MPO(t=22.16,27.01and 32.86) and MDA(t=37.59,42.72 and 59.13) were lower than those in CLP group,also the level of adiponectin(t=14.15,8.10 and 3.19) increased siginificantly(all P<0.05).Conclusion Administration of lovastatin could attenuate lung injury of the sepsis by down-regulate the level of TNF-αand IL-6,with reduced inflam-matory response and oxidative stress,and could upregulate the level of adiponectin in serums of rats with sepsis.
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Objective To evaluate the effects of adiponectin on the mitochondrial damage in septic rats with lung injury .Methods Sixty male Wistar rats ,aged 7-8 weeks ,weighing 180-220 g ,were randomly divided into 3 groups (n=20 each) using a random number table :sham operation group (S group) ,sepsis group (SEP group) and adiponectin group (APN group) .The animals were anesthetized with intraperitoneal 2% pentobarbital sodium 50 mg/kg .Sepsis was produced by cecum ligation and puncture (CLP) .In APN groups ,gene recombinant adiponectin 6 mg/kg was injected intraperitoneally at 12 h after CLP .At 24 h after the operation ,10 rats from each group were chosen and sacrificed ,and lungs were removed for detection of interleukin-6 (IL-6 ) and high-mobility group box-1 (HMGB1 ) contents . The mitochondria of lung samples were isolated for measurement of the malondialdehyde (MDA ) content and degree of mitochondrial swelling and mitochondrial activity . The survival rates within 7 days after operation were recorded in the left 10 rats in each group .Results Compared with S group , IL-6 and HMGB1 contents in lung tissues and MDA content in the mitochondria were significantly increased ,the degree of mitochondrial swelling was increased , and the mitochondrial activity and survival rates within 7 days after operation were decreased in SEP group ( P<0.05 ) . Compared with SEP group , IL-6 and HMGB1 contents in lung tissues and MDA content in the mitochondria were significantly decreased ,the degree of mitochondrial swelling was reduced ,and the mitochondrial activity and survival rates within 7 days after operation were increased in APN groups ( P< 0.05 ) .Conclusion Adiponectin can attenuate lung injury and raise the survival rates in septic rats ,and reduction of mitochondrial damage in lung tissues is involved in the mechanism .
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Objective To evaluate the effect of dexmedetomidine on the expression of 8-Oxoguanine DNA glycosylase 1 (OGG1) mRNA in rat hippocampal neurons subjected to oxygen-glucose deprivation/reoxygenation and restoration (OGD/R).Methods Hippocampal neurons isolated from pathogen-free neonatal Sprague-Dawley rats born within 3 days,were cultured primarily and seeded in 96-well plates (100 μl/well) or 6-well plates (2 ml/well) at the density of 1 × 106 cells/ml.The cells were randomly divided into 5 groups (n=30 each):control group (group C),group OGD/R,and different concentrations of dexmedetomidine groups (DEX1-3 groups).The cells were cultured in normal culture medium in group C and the cells were subjected to OGD/R in the other groups.In DEX1-3 groups,dexmedetomidine with the final concentrations of 0.1,1.0 and 10.0μmol/L were added,respetively,at 2h before OGD.At 24h of restoration,hippocampal neurons were stained with haematoxylin and eosin (H.E) for examination of pathological changes,the cell survival rate was detected by MTT method,the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) were detected by colorimetric method,and the expression of OGG1 mRNA was detected by RT-PCR.Results The pathological changes of neurons were obvious in group OGD/R,and the pathological changes of neurons were significantly mitigated in DEX1,DEX2 and DEX3 groups.Compared with group C,the cell survival rate and SOD activity were significantly decreased,MDA content was increased,and the expression of OGG1 mRNA was down-regulated in OGD/R,DEX1,DEX2 and DEX3 groups (P ＜ 0.05).Compared with group OGD/R,the cell survival rate and SOD activity were significantly increased,MDA content was decreased,and the expression of OGG1 mRNA was up-regulated in DEX1,DEX2 and DEX3 groups (P ＜ 0.05).There was no significant difference in the indices mentioned above between DEX1,DEX2 and DEX3 groups (P ＞ 0.05).Conclusion Dexmedetomidine may protect hippocampal neurons against oxidative stress injury by up-regulating the expression of OGG1 mRNA in rat hippocampal neurons subjected to OGD/R.
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Objective To evaluate the effects of rapamycin combined with rosiglitazone on lung injury in septic rats.Methods One hundred and twenty healthy male Wistar rats were randomly divided into 5 groups (n =6 each):sham operation group (group S); cecum ligation and punture (CLP) group; rapamycin group (group RPM) ; rosiglitazone group (group RGZ) ; rapamycin plus rosiglitazone group (group RPM + RGZ).The rats were anesthetized with intraperitoneal 10% chloral hydrate 100 mg/kg.Sepsis was induced by CLP in groups CLP,RPM,RGZ and RPM + RGZ.At 30 min before CLP,rapamycin 0.4 mg/kg was injected subcutaneously in RPM group,rosiglitazone 0.3 mg/kg was injected via the femoral vein in RGZ group,and rapamycin 0.4 mg/kg was injected subcutaneously and rosiglitazone 0.3 mg/kg was injected via the femoral vein in group RPM + RGZ.While the equal volume of normal saline was given instead in CLP group.Six rats were sacrificed at 2,6,24 and 48 h after CLP in each group,and lungs were removed and cut into sections which were stained with haematoxylin and eosin and examined under microscope.The pathological changes of lungs were scored.The myeloperoxidase (MPO) activity and signal transducer and activator of transcription 3 (STAT3)-DNA binding activity in lung tissues were measured.Results Compared with group S,the pathological scores,MPO activity and STAT3-DNA binding activity were significantly increased in groups CLP,RPM,RGZ,RPM + RGZ (P ＜ 0.05).The pathological scores,MPO activity and STAT3-DNA binding activity were significantly lower in groups RPM,RGZ and RPM +RGZ than in group CLP,and in group RPM + RGZ than in groups RPM and RGZ (P ＜ 0.05).Conclusion Rapamycin combined with rosiglitazone offers additional benefit to attenuating lung injury induced by sepsis over rapamycin or rosiglitazone alone,and inhibition of activation of STAT3 pathway is involved in the mechanism.