1.Effect of butylphthalide injection on serum neuron specific enolase, C-reactive protein and fatty acid binding protein levels in patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage
Shufa ZHENG ; Peisen YAO ; Xiaofen HUANG ; Lianghong YU ; Wei WANG ; Dezhi KANG
Chinese Journal of Biochemical Pharmaceutics 2015;35(10):44-47
To investigate influence of butylphthalide injection on serum neuron specific enolase, C-reactive protein and fatty acid binding protein levels in patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage.Methods Ninety patients with cerebral vasospasm were admitted to The First Affiliated Hospital of Fujian Medical University, then the patients were divided into two groups: The control group (45 patients) was treated with nimodipine and triple-H therapy after surgery;in addition to nimodipine and triple-H therapy, butylphthalide injection was administered to the experimental group(45 patients).Transcranial doppler(TCD)was used for the evaluating cerebral artery blood flow velocity, and the serum neuron specific enolase(NSE), C-reactive protein(CRP) and fatty acid binding protein(FABP) levels in patients with cerebral vasospasm were measured. Results The experimental group improved significantly more than the control group, a significant decrease in cerebral blood flow velocity of the middle cerebral artery in the experimental group as measured by TCD (P<0.05).The serum levels of NSE, CRP and FABP in the patients in the experimental group decreased more significantly (P<0.05).And the incidence of cerebral infarction in experimental group was lower than that in control group (P<0.05).Conclusion The serum levels of NSE, CRP and FABP in the patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage could be significantly reduced by administration of butylphthalide injection, which also could improve cerebral blood supply.Therefore, administration of butylphthalide injection is an effective treatment for cerebral vasospasm.
2.O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells
Hehe CHEN ; Yanhua SHI ; Jiayun YING ; Zhuoya DONG ; Yan WANG ; Yao ZHENG ; Peisen RUAN
Chinese Critical Care Medicine 2023;35(2):164-169
Objective:To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells.Methods:Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. Results:Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2 -ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2 -ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2 -ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2 -ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2 -ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2 -ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2 -ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2 -ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. Compared with the blank control group, the phosphorylation level of Akt in the LPS group was increased. Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2 -ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2 -ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2 -ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2 -ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2 -ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2 -ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2 -ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. Conclusions:The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. AKT may be involved in the effect of LPS on the inhibition of O-GlcNAc modification.
3.Surgical outcomes of focal cortical dysplasia patients with "difficult to locate" intractable epilepsy and their influencing factors
Chengjun LI ; Feng WANG ; Peisen YAO ; Mingxia XU ; Lianghong YU ; Dezhi KANG ; Yuanxiang LIN
Chinese Journal of Neuromedicine 2021;20(8):793-798
Objective:To explore the surgical outcomes of focal cortical dysplasia (FCD) patients with "difficult to locate" intractable epilepsy and their influencing factors.Methods:Thirty-five FCD patients with "difficult to locate" intractable epilepsy, underwent surgical treatment after intracranial electroencephalogram (iEEG) evaluation in our hospital from January 2011 to December 2018, were chosen in our study. Engel grading was used to evaluate the surgical efficacies of these patients, and they were divided into a satisfied efficacy group (Engel grading I) and an incomplete satisfied efficacy group (Engel grading II-IV). The clinical data of patients from the 2 groups were compared. Multivariate Logistic regression analysis was performed to explore the influencing factors for surgical outcomes of FCD patients with "difficult to locate" intractable epilepsy.Results:Of these 35 patients, 26 patients (74.3%) achieved satisfied efficacy, and 4 had incomplete satisfied efficacy. As compared with those in the satisfied efficacy group, patients in the incomplete satisfied efficacy group had significantly lower total resection rate of epileptogenic foci ( P<0.05). Multivariate Logistic regression analysis showed that incomplete resection of epileptogenic foci was the influencing factor for surgical outcomes of FCD patients with "difficult to locate" intractable epilepsy ( P=0.014, OR=0.050, 95%CI: 0.005-0.547). Conclusion:The FCD patients with "difficult to locate" intractable epilepsy can achieve satisfactory results by surgical resection of epileptogenic zones after iEEG monitoring; these FCD patients with "difficult to locate" intractable epilepsy with incomplete resection of epileptogenic foci often have poor surgical outcomes.
4.Research progress in the regulation of autophagy and mitochondrial homeostasis by AMPK signaling channels
Peisen RUAN ; Yao ZHENG ; Zhuoya DONG ; Yan WANG ; Ya'nan XU ; Hehe CHEN
Chinese Critical Care Medicine 2024;36(4):425-429
AMP-activated protein kinase (AMPK) is a widely distributed and evolutionarily conserved serine/threonine protein kinase present in eukaryotic cells. In regulating cellular energy metabolism, AMPK plays an extremely important role as an energy metabolic kinase. When the body is in a low energy state, AMPK is activated in response to changes in intracellular adenine nucleotide levels and is bound to adenosine monophosphate (AMP) or adenosine diphosphate (ADP). Activated AMPK regulates various metabolic processes, including lipid and glucose metabolism and cellular autophagy. AMPK directly promotes autophagy by phosphorylating autophagy-related proteins in the mammalian target of rapamycin complex 1 (mTORC1), serine/threonine protein kinase-dysregulated 51-like kinase 1 (ULK1) and type Ⅲ phosphatidylinositol 3-kinase-vacuolar protein-sorting 34 (PIK3C3-VPS34) complexes. AMPK also indirectly promotes autophagy by regulating the expression of downstream autophagy-related genes of transcription factors such as forkhead box O3 (FOXO3), lysosomal function transcription factor EB (TFEB) and bromodomain protein 4 (BRD4). AMPK also regulates mitochondrial autophagy, induces the division of damaged mitochondria and promotes the transfer of the autophagic response to damaged mitochondria. Another function of AMPK is to regulate mitochondrial health by stimulating mitochondrial biogenesis and participating in various aspects of mitochondrial homeostasis regulation. This review discusses the specific regulation of mitochondrial biology and internal environmental homeostasis by AMPK signaling channels as central to the cellular response to energy stress and regulation of mitochondria, highlighting the key role of AMPK in regulating cellular autophagy and mitochondrial autophagy, as well as advances in research on the regulation of mitochondrial homeostasis.
5.Clinical efficacy of meropenem by different infusion therapies in treatment of severe sepsis in children
Yu HAN ; Peisen RUAN ; Yao ZHENG ; Yinquan XU ; Hehe CHEN
China Modern Doctor 2024;62(29):73-76
Objective To evaluate the clinical efficacy and clearance rate of pathogens of meropenem by different infusion therapies in treatment of severe sepsis for pediatric patients.Methods Sixty inpatients with serious sepsis from Pediatric Intensive Care Unit,Women and Children's Hospital of Ningbo University were randomly divided into three groups 20 in each.The meropenem was given according to the recommended therapeutic dose.Group A:The micropump was pumped for 0.5h at a rate of 100ml/h.Group B:The micropump was pumped for 3h at a rate of 16.7ml/h.Group C:Half of the menopenen was pumped for 0.5h at a rate of 50ml/h,and the other half was pumped for 2.5h at a rate of 10ml/h.Changes of indexes were compared before and after the treatment to estimate of the clinical effective rate,clearance rate of pathogens and side effects among the groups.Results There were observable improvements in the inflammatory indicators after treatment,such as white cell count,C-reactive protein and procalcitonin,etc.The total effective rate was 60%in group A,75%in group B,and 95%in group C.There were statistically differences among the groups(P<0.05).Meanwhile,the bacterial clearance rates of the groups were 50%(group A),70%(group B)and 100%(group C),respectively(P<0.05).The rate of side effect was 20%(group A),15%(group B)and 20%(group C),respectively(P>0.05).Conclusion It can significantly improve the clinical efficacy and antibacterial efficacy by the two step infusion therapy of meropenem,compared with traditional infusion therapy and extended infusion.
6.Effect of Porcine Large Intestine-processed Dahuang (Radix et Rhizoma Rhei) on Defecation and Colon Pathological Changes in Constipation Model Mice
Xiaotian RAO ; Linjin HUANG ; Peisen ZHENG ; Bangyang CHEN ; Dianwei WU ; Maosheng HUANG ; Qiuming CHEN ; Dongjin HUANG ; Hongyue ZHAN ; Yinghua YAO ; Chao CHEN
Journal of Traditional Chinese Medicine 2023;64(18):1916-1921
ObjectiveTo investigate the effect of porcine large intestine-processed Dahuang (Radix et Rhizoma Rhei) on defecation in constipation model mice and the possible mechanism. MethodsFifty Kunming mice were randomized to blank group (n=10) and model group (n=40). Loperamide suspension at the dose of 8 mg/(kg·d) was given by gavage for four consecutive days to establish a model of constipation. The 24 successfully modeled mice were randomly divided into model group, processed Dahuang group, lactulose group, raw Dahuang group, with six mice in each group. Moreover, six randomly selected mice were chosen as control group. Since the fifth day, 8 mg/(kg·d) of loperamide suspension by gavage was given to the model group, processed Dahuang group, raw Dahuang group, and lactulose group; two hours later, the processed and raw Dahuang groups were administered with 0.6 g/(kg·d) of processed and raw Dahuang suspension, respectively, while the lactulose group was given 0.6 g/(kg·d) of latulose suspension, and the blank group and the model group were given 0.2 ml/10 g of distilled water by gavage, all for four days. The general condition, body weight after the last gavage, number of fecal particles within six hours, fecal wet weight, fecal water content ratio, intestinal propulsion rate and colonic histology changes by HE staining of each group were detected. ResultsThe body weight of the mice in the raw Dahuang group was significantly lighter than that in the other groups (P<0.05 or P<0.01). The number of fecal particles, fecal wet weight and intestinal propulsion rate of mice significantly decreased in the model group than in the blank group (P<0.05 or P<0.01). Compared to those in the model group, the number of fecal particles and fecal wet weight in the processed Dahuang group, lactulose group and raw Dahuang group significantly increased, and the fecal water content ratio in the raw Dahuang group increased as well (P<0.05 or P<0.01). Compared to those in the processed Dahuang group, the number of fecal particles and fecal wet weight in the raw Dahuang group decreased, while the fecal water content ratio increased (P<0.05 or P<0.01), and the fecal water content ratio in the lactulose group increased significantly (P<0.05). The intestinal propulsion rate in the processed Dahuang group was higher than that in the model group, lactulose group and raw Dahuang group (P<0.05 or P<0.01). Histopathological analysis showed that the colonic crypts and goblet cells in the blank group were normal and clear, and the colonic muscular layer was thicker. The colonic crypts of the mice in the model group were damaged, with reduced goblet cells to varying degrees and changed colonic muscularis. In the lactulose group and raw Dahuang group, part of the crypts were broken, and the goblet cells were damaged to varying degrees, while in the processed Dahuang group, still the colonic tissue structure of the mice was relatively clear, and the colonic crypts and goblet cells were relatively normal, with thickened muscular layer of the colon. ConclusionPorcine large intestine-processed Dahuang could improve defecation in constipation model mice, and reduce the drastic purgation function of raw Dahuang, for which the mechanism may be related to the protection of colon histopathological damage.