1.Effect of carboxyamidotriazole-orotate on proliferation and fatty acid anabolism of human pancreatic cancer cell lines
Hongjiang GUO ; Yeting XU ; Diya ZHANG ; Jiaxing QIU ; Yucheng WANG ; Rui JU ; Lei GUO
Basic & Clinical Medicine 2024;44(4):440-446
Objective To study the effect of carboxyamidotriazole-orotate(CTO)on the proliferation and fatty acid anabolism regulation of human pancreatic cancer cells.Methods Human pancreatic cancer cell lines AsPC-1,AsPC-1/GEM(AR),PANC-1 and MiaPaCa-2 were used as the study subjects;cell survival rate was detected by sulfo-nylrhodamine B(SRB);the mRNA level of key genes for fatty acid synthesis was detected by qPCR;the protein level of the AMPK/ACC pathway was detected by Western blot;intracellular lipid metabolites were examined by liquid chromatography-mass spectrometry(LC-MS).Results Comparing to control group,CTO significantly de-creased the cell viability of AsPC-1,AR,PANC-1,and MiaPaCa-2(P<0.05).CTO down-regulated the mRNA level of key fatty acid synthesis genes(P<0.05).CTO significantly reduced the protein expression of AMPK,ACC and c-Myc(P<0.05),while increasing the protein expression of p-AMPK and p-ACC(P<0.05).CTO decreased lipid metabolite content in AR cells(P<0.05).Conclusions CTO attenuates cellular fatty acid anabolism by inhibition of oncogene c-Myc expression and AMPK/ACC pathway,down-regulates the expression of fatty acid synthesis-related genes,and then inhibits proliferation of the human pancreatic cancer cell lines AsPC-1,AR,PANC-1 and MiaPaCa-2.
2.Application of quantitative electroencephalogram trends in the assessment of the state of brain function in patients with severe stenosis of the internal carotid artery and its predictive value for the risk of acute occlusion in the short term(report of one case)
Siyao JI ; Yan WANG ; Yeting LU
Journal of Clinical Neurology 2024;37(1):26-30
Objective To explore the application of quantitative EEG(QEEG)trends in the assessment of the state of brain function in patients with severe stenosis of the internal carotid artery and its predictive value for the risk of acute occlusion in the short term.Methods The clinical and imaging data of a case of severe left internal carotid stenosis were retrospectively analyzed,and QEEG trends were used for evaluating the state of brain function.Results It showed that rhythmicity spectrogram,amplitude-integrated EEG,fast Fourier transformation spectrogram and fast Fourier transform power spectrum in QEEG trends could quickly and visually display theta activity and amplitude at the side of severe internal carotid artery stenosis continued to increase compared with the healthy side hemisphere.Acute occlusion of the left internal carotid artery and large artery atherosclerotic cerebral infarction occurred in the patient after 3 days.Conclusion As a supplement to neuroimaging examination,QEEG trends may be helpful for rapidly diagnosing brain function damage in the early stage of patients with severe internal carotid artery stenosis who are under the ischemic attack state,and even have potential predictive values for patients with acute occlusion in the short term.
3.Bmal1 mediates the neuroprotective effect of sodium butyrate in a mouse model of Parkinson's disease
Feixia WANG ; Zheng ZHANG ; Yan SUN ; Liujing YANG ; Tongtong GUO ; Yeting PAN ; Songtao DING ; Lin JIANG ; Handeng LIU
Journal of Southern Medical University 2024;44(5):876-884
Objective To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate(NaB)in a mouse model of Parkinson's disease(PD)via the gut-brain axis.Methods Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group,PD model group,and NaB treatment group.In the latter two groups,PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once daily for 5 consecutive days,and normal saline was injected in the control group.After modeling,the mice received daily gavage of NaB(300 mg/kg)or an equal volume of saline for 14 days.Behavioral tests were carried out to assess the changes in motor function of the mice,and Western blotting was performed to detect the expressions of tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the striatum and nuclear factor-κB(NF-κB),tumor necrosis factor(TNF-α),interleukin 6(IL-6),and the tight junction proteins ZO-1,Occludin,and Claudinin the colon.HE staining was used to observe inflammatory cell infiltration in the colon of the mice.RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues,and their expressions were verified using qRT-PCR and Western blotting.Results The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH,Occludin,and Claudin and downregulated expressions of α-syn,NF-κB,TNF-α,and IL-6(all P<0.05).HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice.RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice(P<0.05).Conclusion NaB can improve motor dysfunction,reduce dopaminergic neuron loss in the striatum,and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.
4.Bmal1 mediates the neuroprotective effect of sodium butyrate in a mouse model of Parkinson's disease
Feixia WANG ; Zheng ZHANG ; Yan SUN ; Liujing YANG ; Tongtong GUO ; Yeting PAN ; Songtao DING ; Lin JIANG ; Handeng LIU
Journal of Southern Medical University 2024;44(5):876-884
Objective To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate(NaB)in a mouse model of Parkinson's disease(PD)via the gut-brain axis.Methods Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group,PD model group,and NaB treatment group.In the latter two groups,PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once daily for 5 consecutive days,and normal saline was injected in the control group.After modeling,the mice received daily gavage of NaB(300 mg/kg)or an equal volume of saline for 14 days.Behavioral tests were carried out to assess the changes in motor function of the mice,and Western blotting was performed to detect the expressions of tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the striatum and nuclear factor-κB(NF-κB),tumor necrosis factor(TNF-α),interleukin 6(IL-6),and the tight junction proteins ZO-1,Occludin,and Claudinin the colon.HE staining was used to observe inflammatory cell infiltration in the colon of the mice.RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues,and their expressions were verified using qRT-PCR and Western blotting.Results The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH,Occludin,and Claudin and downregulated expressions of α-syn,NF-κB,TNF-α,and IL-6(all P<0.05).HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice.RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice(P<0.05).Conclusion NaB can improve motor dysfunction,reduce dopaminergic neuron loss in the striatum,and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.
5.Analysis of traffic accidents caused by epileptic seizures in 7 patients without definite diagnosis
Jiayin LI ; Siyao JI ; Yan WANG ; Yeting LU ; Xiangyi ZHU ; Shengjie PAN ; Min XU ; Yan LI ; Xiaowei HU
Chinese Journal of Neurology 2023;56(5):521-525
Objective:To elucidate the phenomenon that epileptic seizure occurs in patients with epilepsy without definite diagnosis when driving a motor vehicle and its hazards.Methods:From January 2020 to June 2022, 7 epileptic patients who experienced traffic accidents caused by seizures were selected from the First Affiliated Hospital of Soochow University, and their demographic data, traffic accident related data and epilepsy diagnosis and treatment data were summarized and analyzed.Results:A total of 7 adult patients with epilepsy were collected, including 6 males, 4 of whom had been driving for more than 10 years. Among them, 1 patient drove a bus, and the other 6 patients drove private cars. Totally 5/7 of the accidents resulted in personal injury, and 3/7 of the accidents resulted in personal death. In 5 patients, video electroencephalogram showed interictal epileptiform discharges. In 2 patients, the imaging findings suggested the presence of cerebral cortical lesions that may lead to seizures. In terms of the form of seizure, 3 patients′ seizure type was focal to bilateral tonic-clonic, and the other 4 patients were very probable to be focal impaired awareness seizure.Conclusions:Undiagnosed epileptic seizures lead to traffic accidents, endanger patients and public safety, which need to attract attention from both doctors and patients, as well as the whole society.
6.Value of ultrasound in the diagnosis of intraneural perineurioma
Tiezheng WANG ; Hengtao QI ; Zhibo LIU ; Zhidian HOU ; Yeting WANG ; Wen CHEN ; Jianbo TENG
Chinese Journal of Ultrasonography 2023;32(7):627-630
Objective:To investigate the value of ultrasound in the diagnosis of intraneural perineurioma.Methods:From June 2015 to June 2022, 11 patients with intraneural perineurioma confirmed by surgery or biopsy in Provincial Hospital Affiliated to Shandong First Medical University were retrospectively collected, all of whom underwent high-frequency ultrasound examination. Clinical data and sonographic characteristics were collected. The maximum cross-sectional area of the affected nerve was recorded and compared with the corresponding site of the contralateral nerve.Results:All the 11 cases of intraneural perineurioma were single neuropathy. The sonogram showed that the affected nerve was spindle shaped and thickened. There was a statistical difference between the maximum cross-sectional area of the thickened intraneural perineurioma and the corresponding site of the contralateral nerve [(0.158±0.043)cm vs (0.044±0.012)cm, t=8.669, P<0.001]. The fascicles of the affected nerve were thickened with loss of normal fascicular definition, but there were still hyperechoic linear separation among the fascicles. Conclusions:High-frequency ultrasound may be a valuable technique for the diagnosis of intraneural perineurioma.
7.Emergency multimodal computed tomography for the diagnosis of stroke mimic--epileptic seizure
Xiaowei Hu ; Shicun Huang ; Ziwei Lu ; Feirong Yao ; Yiqing Wang ; Yeting Lu ; Xiangyi Zhu ; Min Xu ; Qi Fang
Neurology Asia 2020;25(3):269-277
Background and Objectives: Stroke mimics are medical conditions producing stroke-like symptoms
but eventually get diagnosed as non-stroke diseases. Epileptic seizure is a common type of stroke
mimic. The purpose of this study is to investigate the application of emergency multimodal computed
tomography (CT) in the diagnosis of epileptic seizure. Methods: We retrospectively reviewed the case
group of patients with suspected stroke in the emergency stroke care service of the First Affiliated
Hospital of Suzhou University from September 2017 to October 2019. We included those who underwent
multimodal CT, including non-contrasted cranial CT, CT perfusion with CT angiography, and were
ultimately diagnosed as epileptic seizures. Ten patients with acute anterior circulation ischemic stroke
were assigned as controls. Results: A total of five cases met the inclusion criteria. Multimodal CT was
completed within 2.25 to 3.50h from symptom onset. On CT perfusion, hyperperfusion was shown in
four cases and slightly increased perfusion in one case with epileptic seizures. Cerebral blood flow
and cerebral blood volume were significantly increased, while time to peak and mean transit time
decreased in the regions of interest of the epileptic hemisphere when compared to either the non-affected hemisphere or the ischemic area in the control group (P<0.05). The abnormal perfusion areas did not follow vascular territory supply and CT angiography did not show vessel occlusion in the case group.
Conclusion: Emergency multimodal CT could be used effectively to differentiate epileptic seizure
from stroke.
8.Comparison of risk of death between older and non-older critical patients in ICU: a retrospective cohort study of consecutive 3 years
Yeting ZHOU ; Daoming TONG ; Shaodan WANG ; Liansong LIU ; Song YE ; Benwen XU
Chinese Critical Care Medicine 2017;29(5):448-452
Objective To investigate the risk of death between older and non-older critical patients in intensive care unit (ICU) in Shuyang People's Hospital.Methods A retrospective cohort study was conducted. The critical patients who aged 15 or above, and admitted to ICU of Shuyang People's Hospital from January 2014 to December 2016 were enrolled, and all the data was collected from theregistration and electronic medical records in the ICU. The prevalence and causes of death in ICU critical patients during the study period were observed. The patients were divided into elderly group (65 years and older) and non-elderly group (15-65 years), and logistic regression analysis was performed for the risk of death in the two groups.Results During the study period, 2707 critical patients in emergency were admitted to the ICU of Shuyang People's Hospital, and patients not satisfied the inclusion criteria were excluded. Finally, a total of 2466 patients were enrolled in the analysis with the male and female ratio of 1.6 : 1, an average age of (61.8±17.3) years, a median Glasgow coma scale (GCS) score of 6 (4, 8), and with a median ICU stay of 3 (1, 6) days. In 2466 critical patients, the most common cause of critical state was spontaneous intracerebral hemorrhage (25.5%) and traumatic brain injury (17.0%), with a fatality rate of 46.0% and 39.5% within first 7 days respectively. Compared with the non-elderly patients (n = 1415), the incidences of death of the elderly patients (n = 1051) due to traumatic brain injury, cerebral infarction, heart failure/cardiovascularcrisis, and respiratory critically ill were significantly increased (9.4% vs. 4.7%, 2.9% vs. 0.8%, 5.0% vs. 2.1%, 2.5% vs. 1.0%, respectively), while the incidence of death for pesticide/drug poisoning in the elderly group was significantly lower than that in the non-elderly group (0.2% vs. 1.2%, allP < 0.01). Stepwise logistic regression analysis showed that traumatic brain injury [hazard ratio (HR) = 1.878, 95% confidence interval (95%CI) = 1.233-2.864,P = 0.003), cerebral infarction (HR = 0.435, 95%CI = 0.229-0.826, P = 0.011), heart failure/cardiovascular crisis (HR = 0.399, 95%CI = 0.238-0.668,P = 0.000), and respiratory critically ill (HR = 0.239, 95%CI = 0.126-0.453,P= 0.000) in the older patients were significantly high risk factors of death as compared with those in non-older patients.Conclusions In the general ICU, the most common cause is spontaneous intracerebral hemorrhage and traumatic brain injury in critical patients with a high fatality rate. The risk of death in elderly patients with severe traumatic brain injury, cerebral infarction, heart failure/cardiovascular crisis, respiratory critically ill is higher than that of the non-elderly patients.
9.Sepsis associated encephalopathy is an independently risk factor for nosocomial coma in patients with supratentorial intracerebral hemorrhage:a retrospective cohort study of 261 patients
Guangsheng WANG ; Shaodan WANG ; Yeting ZHOU ; Xiaodong CHEN ; Xiaobo MA ; Daoming TONG
Chinese Critical Care Medicine 2016;28(8):723-728
Objective To investigate whether the presence of sepsis associated encephalopathy (SAE) would predict nosocomial coma (NC) and poor outcome in patients with supratentorial intracerebral hemorrhage (SICH). Methods A retrospective cohort study was conducted. The adult acute SICH patients with or without coma admitted to intensive care unit (ICU) of Shuyang People' Hospital Affiliated to Xuzhou Medical University from December 2012 to December 2015 were enrolled. Brain computed tomography (CT) scans were analyzed and the patients were divided into pre-hospital coma (PC) and NC groups. The clinical data and the incidence of SAE of patients in two groups were compared, and the 30-day prognosis was followed up. Univariate and Cox regression analyses were performed to analyze whether SAE would predict NC and poor outcome in patients with SICH. Results A total of 330 patients with acute SICH and coma were enrolled, excluding 60 cases of infratentorial cerebral hemorrhage, 3 cases of primary intraventricular hemorrhage, and 6 cases of unknown volume hematoma. Finally, 261 patients were included, with 111 patients of NC events, and 150 patients of PC events. 69 (62.2%) SAE in SICH with NC and 33 (22.2%) SAE in SICH with PC was diagnosed, and the incidence of SAE between two groups was statistically significant (P < 0.01). Compared with PC group, SICH patients in the NC group had lower incidence of hypertension (81.1% vs. 96.0%), longer time from onset to NC [days: 2.3 (23.9) vs. 0 (0.5)] and length of ICU stay [days: 5.0 (34.0) vs. 3.0 (12.0)], higher initial Glasgow coma score (GCS, 10.2±1.5 vs. 6.6±1.6) and sequential organ failure assessment (SOFA) score [4.0 (6.0) vs. 3.0 (3.0)], lower initial National Institutes of Health Stroke Scale (NIHSS) score (19.4±6.6 vs. 30.2±6.8), as well as more frequent sepsis (78.4% vs. 38.0%), vegetative state (24.3% vs. 14.0%), acute respiratory failure (24.3% vs. 10.0%), pneumonia (37.8% vs. 24.0%), septic shock (8.1% vs. 0), acute liver failure (5.4% vs. 0), hypernatremia (8.1% vs. 0), CT indicating that more frequent vasogenic edema (64.9% vs. 16.0%) and white matter lesion (13.5% vs. 2.0%), and less mannitol usage (94.6% vs. 100.0%), and less brain midline shift (32.4% vs. 68.0%) and hematoma enlargement (8.1% vs. 30.0%), less hematoma volume (mL: 28.0±18.8 vs. 38.3±24.4) in CT, and higher 30-day mortality (54.1% vs. 26.0%) with statistical differences (all P < 0.05). It was shown by Cox regression analyses that SAE [hazard ratio (HR) = 3.5, 95% confidence interval (95%CI) = 1.346-6.765, P = 0.000] and SOFA score (HR = 1.8, 95%CI = 1.073-1.756, P = 0.008) were independent risk factors of death of SICH patients with NC, and hematoma enlargement was independent risk factor of death of SICH patients with PC (HR = 3.0, 95%CI = 1.313-5.814, P = 0.000). Conclusion SAE is the independent factor of inducing NC event and poor prognosis in SICH patients.
10.Diagnosis of sepsis associated encephalopathy:a retrospective analysis of 6 patients
Shaodan WANG ; Guangsheng WANG ; Yeting ZHOU ; Xiaodong CHEN ; Tonghui YANG ; Yantao LIANG ; Daoming TONG
Chinese Journal of Primary Medicine and Pharmacy 2016;23(19):2941-2945
Objective To investigate whether the presence of infection in a case series with coma would predict sepsis associated encephalopathy(SAE).Methods From Jan 2013 to Oct 2014,we used the criteria of systemic inflammatory response syndrome (SIRS)positive sepsis with encephalopathy and retrospective diagnosed a comatose case series with infection and from a tertiary teaching hospital intensive care unit (ICU).Results Among 6 comatose patients with evidence of infection,3 cases were secondary infection after hemorrhagic stroke,1 case was secondary infection after trauma,and the other 2 cases were primary infection.All patients met the diagnosis of SIRS -positive sepsis with encephalopathy.Among them,the presence of SIRS 3 criteria was in 2 cases,four criteria in 4 cases. All patients with severe brain failure (100%),in addition to 5 cases with acute respiratory failure caused by lung injury,one case with acute liver failure.Brain imaging confirmed that the delayed vasogenic edema was in two cases (33.3%),the cerebral ischemic lesions in four cases(66.7%).The ischemic lesion included 1 patient with minor infarcts and 1 case with mild white matter lesions,and with a good prognosis.The other two ischemic cases included multifocal leukoencephalopathy with central pontine myelinolysis in 1 case and extensive white matter lesions in 1 case,eventually with a poor prognosis.Conclusion SAE is a common critically illness,the use of the new classifi-cation criteria of sepsis is helpful in the diagnosis of sepsis associated encephalopathy.


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