AIM:To detect the effect and underlying mechanism of parthenolide ( PN) on neointimal hyperpla-sia.METHODS:After 1 week of high-fat feeding, 30 male New Zealand white rabbits (2.0~2.3 kg) were randomly di-vided into 6 groups: sham +NS, rabbits received 0.9% normal saline after sham operation; sham +DMSO, rabbits re-ceived DMSO after sham operation;balloon injury(BI)+NS, rabbits received NS after balloon injury;BI+DMSO, rabbits received DMSO after balloon injury;BI+PN low, rabbits received PN at 1 mg/kg after balloon injury;BI+PN high, rab-bits received PN at 2 mg/kg after balloon injury .The drugs were intraperitoneal injected once a day after the operation until sacrifice.After fed with high-fat diet for 4 weeks, the intima-media thickness, the expression of caspase-1, IL-1β, the lev-els of IL-8, TC, TG, LDL and HDL in the serum were measured .RESULTS:Compared with sham +DMSO group, the thickness of intima, the amount of caspase-1, IL-1βand IL-8 in BI +DMSO group were significantly increased ( P <0.05).The levels of caspase-1, IL-1βand IL-8 were significantly decreased in BI +PN high group compared with BI +DMSO group (P<0.05).CONCLUSION:Neointimal hyperplasia is suppressed by PN after balloon injury , the potential mechanism may be associated with its anti-inflammatory role .

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BACKGROUNDMethylenetetrahydrofolate reductase (MTHFR) plays an important role in metabolism of folate and DNA methylation. In vitro, many studies have demonstrated that abnormal methylation of some genes may affect the sensitivity of tumor cells to cytotoxic drugs and agents interfering with DNA synthesis. The aim of this study is to investigate the relationship between genetic polymorphisms of MTHFR C677T or A1298C and the response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC).

METHODSA total of 97 patients with NSCLC were analyzed. MTHFR genotypes were detected in all the patients by PCR-RFLP method. All the patients were treated with platinum-based chemotherapy.

RESULTS(1) Out of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 34.0%, 50.5% and 15.5%, respectively, while the frequencies of MTHFR A1298C A/A, A/C and C/C genotypes were 64.6%, 29.2% and 6.3%, respectively. The overall response rate (complete and partial response) to platinum-based chemotherapy was 39.2%. (2) No significant difference in response rate to chemotherapy was observed according to the MTHFR C677T or A1298C genotypes. However, MTHFR C677T and A1298C polymorphisms showed a synergic effect on chemotherapeutic efficacy, the response rate of patients with MTHFR C677T T allele and A1298C A/A genotype (51.1%) was significantly higher than those with MTHFR C677T C/T and A1298C C allele (12.5%)(P=0.007, OR=7.30, 95% CI: 1.34-52.47).

CONCLUSIONSThe results suggest that the synergic effect between MTHFR C677T and A1298C polymorphisms is associated with clinical response to platinum-based chemotherapy. Detection of MTHFR genotypes may indicate the sensitivity of NSCLC patients to platinum-based chemotherapy.

Objective:To explore whether circular RNA HECTD1 (circ-HECTD1) is involved in oxygen-glucose deprivation (OGD)-induced neuronal cell damage by regulating the expressions of miR-98-5p/ephrin A4 (EPHA4).Methods:Mouse primary cortical neuronal cells were isolated and cultured in vitro. The targeting relations of circ-HECTD1 and miR-98-5p with EPHA4 were detected by dual luciferase reporter assay and RNA binding protein immunoprecipitation assay. These neurons were randomly divided into control group (cultured for 24 h under normal condition) and 6, 12 and 24 h OGD treatment groups (treated with OGD for 6, 12 and 24 h, respectively), OGD+Vector group and OGD+circ-HECTD1 group, OGD+small interfering RNA (siRNA) negative control (si-NC) group and OGD+siRNA circ-HECTD1 (si-circ-HECTD1) group, OGD+micro RNA (miR) negative control (miRNC) group and OGD+miR-98-5p mimic group, OGD+miRNA inhibitor negative control (anti-miRNC) group and OGD+miR-98-5p inhibitor (anti-miR-98-5p) group, OGD+miR-98-5p mimic+pcDNA group and OGD+miR-98-5p mimic+EPHA4 group, OGD+si-circ-HECTD1+anti-miR-NC group and OGD+si-circ-HECTD1+miR-98-5p inhibitor group; pCD5-ciR empty vector, pCD5-ciR-circ-HECTD1, si-NC, si-circ-HECTD1, miR-NC, miR-98-5p mimic, anti-miR-NC or anti-miR-98-5p were transfected into the neurons, and miR-98-5p mimi and pcDNA3.1 empty vector, miR-98-5p mimic and pcDNA3.1-EPHA4 overexpression vector, si-circ-HECTD1 and anti-miR-NC, or si-circ-HECTD1 and anti-miR-98-5p were co-transfected into the neurons. After 24 h of OGD treatment, the circ-HECTD1, miR-98-5p and EPHA4 mRNA expressions were detected by real-time fluorescent quantitative PCR (qRT-PCR), the EPHA4 protein expression was detected by Western blotting, the proliferation activity was detected by MTT assay, the apoptosis rate was detected by flow cytometry, the levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in cell culture medium were detected by ELISA, and the activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by kit assay. Results:(1) Targeting relations between circ-HECTD1 and miR-98-5p, and EPHA4 and miR-98-5p were verified. (2) As compared with the control group, the neurons in 6, 12 and 24 h OGD treatment groups had significantly increased circ-HECTD1 and EPHA4 protein expressions and significantly decreased miR-98-5p expression ( P<0.05). (3) As compared with OGD+Vector group, OGD+circ-HECTD1 group had significantly increased circ-HECTD1 expression, and significantly decreased miR-98-5p expression ( P<0.05); as compared with OGD+si-NC group, OGD+si-circ-HECTD1 group had significantly increased miR-98-5p expression, and significantly decreased EPHA4 mRNA and protein expressions ( P<0.05); as compared with OGD+miR-NC group, OGD+miR-98-5p mimic group had significantly increased miR-98-5p expression, and significantly decreased EPHA4 protein expression ( P<0.05); as compared with OGD+anti-miR-NC group, OGD+anti-miR-98-5p group had significantly decreased miR-98-5p expression, and significantly increased EPHA4 protein expression ( P<0.05); as compared with the OGD+si-circ-HECTD1+anti-miR-NC group, OGD+si-circ-HECTD1+anti-miR-98-5p group had significantly increased EPHA4 mRNA and protein expressions ( P<0.05). (4) As compared with the control group, the OGD groups had significantly decreased cell viability and SOD activity, and significantly increased IL-1β and TNF-α levels, apoptosis rate and MDA activity ( P<0.05); as compared with the OGD+si-NC group, the OGD+si-circ-HECTD1 group had significantly decreased cell apoptosis rate, IL-1β and TNF-α levels, and MDA activity, and significantly increased cell viability and SOD activity ( P<0.05); as compared with the OGD+si-circ-HECTD1+anti-miR-NC group, the OGD+si-circ-HECTD1+anti-miR-98-5p group had significantly decreased cell viability and SOD activity, and significantly increased IL-1β and TNF-α levels, apoptosis rate and MDA activity ( P<0.05); as compared with the OGD+miR-NC group, OGD+miR-98-5p mimic group had significantly decreased cell apoptosis rate, IL-1β and TNF-α levels, and MDA activity, and significantly increased cell viability and SOD activity ( P<0.05); as compared with OGD+miR-98-5p mimic+pcDNA group, OGD+miR-98-5p mimic+EPHA4 group has significantly increased cell apoptosis rate, IL-1β and TNF-α levels, and MDA activity, and significantly increased cell viability and SOD activity ( P<0.05). Conclusion:Knockdown of circ-HECTD1 could ameliorate the OGD-induced neuronal cell damage in mice by targeting the expressions of miR-98-5p/EPHA4.

Objective To investigate the effect of targeting TRIM63 in regulating oxidative stress pathways and im-proving blood-brain barrier injury and neurological recovery after acute stroke.Methods Adult male C57 mice were ran-domly divided into Sham group,Vehicle group,and Myomed-205 group,and a mouse model of transient middle cerebral artery occlusion(tMCAO)was constructed.After removal of the suture,the mice in the Myomed-205 group and the Ve-hicle group were given intraperitoneal injection of TRIM63 inhibitor,and those in the Sham group were given intraperito-neal injection of an equal volume of solvent.On day 3 of reperfusion,TTC staining was used to observe cerebral infarct vol-ume,neurological score was used to evaluate neurological recovery,and the dry-wet weight method was used to measure brain water content.Reactive oxygen species(ROS),superoxide dismutase(SOD),glutathione(GSH),and malondial-dehyde(MDA)kits were used to measure the content of oxidative stress indices in brain.The Evans Blue method was used to observe blood-brain barrier injury,and Western blotting was used to measure the protein expression levels of ZO-1 and Occludin.Results Compared with the Vehicle group,the Myomed-205 group had a significant reduction in cerebral infarct volume(P<0.05),and compared with the control group,the 100 mg/ml Myomed-205 treatment group had signifi-cant reductions in neurological score(P<0.05)and brain water content(P<0.05).Compared with the Vehicle group,the Myomed-205 group had a significant reduction in the number of ROS-positive cells on days 3,7,and 14 after stroke(P<0.05),and compared with the control group,the Myomed-205 group had a significant reduction in the expression level of the pro-oxidative stress index MDA(P<0.05)and significant increases in the expression levels of the antioxidant indices GSH and SOD(P<0.05).Compared with the Vehicle group,the Myomed-205 group had a significant reduction in EB leakage on days 7 and 14 after stroke(P<0.05)and significant increases in the protein expression levels of ZO-1 and Occludin(P<0.05).Conclusion Inhibition of the TRIM63 signaling pathway can promote neurological recovery after cerebral ischemic stroke in mice,which may be achieved by alleviating oxidative stress and blood-brain barrier injury.

OBJECTIVEIn order to study the relation between polymorphisms of methylenetetrahydrofolate reductase C677T (MTHFR) and susceptibility of stomach cancer (SC).

METHODSWe conducted a case-control study with 107 cases of SC and 200 population-based controls in Huaian city of Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR genotypes were detected by PCR-RFLP method.

RESULTS(1) The frequency of MTHFR variant genotypes (C/T + T/T) among the cases (79.4%) was significantly higher than the controls (68.5%) (P = 0.041 6); the crude OR for SC was 1.78 (95% CI: 0.99 - 3.22). After adjustment for sex and age, the OR for SC was 1.89 (95% CI: 1.08 - 3.32). (2) Subjects who had MTHFR variant genotypes and having smoking habit were at a significantly higher risk of developing SC (OR = 7.72, 95% CI: 2.23 - 26.79) compared with those who had wild-type homozygotes (C/C) genotype and no smoking habit. Individuals who had variant genotypes and who had habit of frequent alcohol drinking were at an increased risk of developing SC (OR = 3.08, 95% CI: 1.30 - 7.23) compared with those with C/C genotype and low consumption of alcohol. As compared with subjects with C/C genotype and low consumption of alcohol and no smoking habit, individuals who had variant genotypes and who had habits of frequent alcohol drinking and smoking had 12.96 (95% CI: 2.76 - 70.46) folds risk developing SC.

CONCLUSIONSThese results in the present study suggested that the polymorphisms of MTHFR C677T was associated with risk of developing SC, and there was a coordinated effect between MTHFR genotypes and habits of smoking and alcohol drinking in the development of SC.

Alcohol Drinking ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; Middle Aged ; Oxidoreductases Acting on CH-NH Group Donors ; genetics ; Point Mutation ; Polymorphism, Genetic ; Risk Factors ; Smoking ; Stomach Neoplasms ; epidemiology ; genetics

Objectives: To explore weather oxygen uptake efficiency slope (OUES) may predict the prognosis in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods: The consecutive newly diagnosed IPAH patients in our hospital from 2010-11 to 2015-06 were prospectively enrolled and regular follow-up study was conducted to record cardiovascular events (death and lung transplantation). Kaplan–Meier curve, uni- and multivariate Cox regression analysis were performed to assess the survival rate in relevant patients. Results: A total of 210 IPAH patients at the mean age of (32±10) years were finished cardiopulmonary exercise test (CPET) and received regular follow-up study including 159 female. There were 31 patients died and 1 received lung transplantation over 41 months follow-up period. OUES was positively related to peak oxygen uptake (VO2)/body weight (r=0.71, P<0.0001). Multivariate analysis demonstrated that OUESI and NT-proBNP could independently predict the prognosis of IPAH patients. The 5-year survival rate in patients with OUESI≤0.52 L/(min?m2) was lower than those with OUESI>0.52 L/(min?m2) (41.9% vs 89.8%), P<0.0001.Conclusion: OUES as a submaximal CPET parameter may well predict the prognosis in IPAH patients.

Objective:To investigate the clinical significance of fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) in patients with chronic atherosclerotic middle cerebral artery occlusion.Methods:From July 2016 to November 2020, patients admitted to the Department of Neurology, Jiangdu People's Hospital of Yangzhou and first found chronic atherosclerotic middle cerebral artery occlusion were enrolled. The demographic, clinical and MRI imaging data were collected. According to the presence or absence of acute cerebral infarction, they were divided into the non-acute cerebral infarction group and the acute cerebral infarction group. According to the modified Rankin Scale score at 3 months after the onset, patients with acute cerebral infarction were further divided into the good outcome group (≤2) and the poor outcome group (>2). A multivariate logistic regression model was used to analyze the independent correlation between FVHs and the risk of cerebral infarction in patients with chronic atherosclerotic middle cerebral artery occlusion and the outcome in patients with cerebral infarction. Results:A total of 94 patients with chronic atherosclerotic middle cerebral artery occlusion were enrolled, including 38 with non-acute cerebral infarction (40.4%) and 56 with acute cerebral infarction (59.6%). In patients with acute cerebral infarction, 13 (23.2%) had a poor outcome, and 43 (76.8%) had a good outcome. The fibrinogen level, the proportion of patients with FVHs and the FVHs score in the cerebral infarction group were significantly higher than those in the non-cerebral infarction group (all P<0.05). Multivariate logistic regression analysis showed that the FVHs score was significantly, independently, and positively correlated with the risk of acute cerebral infarction (odds ratio 2.524, 95% confidence interval 1.400-4.552; P=0.002). The National Institutes of Health Stroke Scale score at admission, the modified Rankin Scale score at admission, and FVHs score in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that there was a significant independent negative correlation between the FVHs score and the outcome of patients with cerebral infarction (odds ratio 0.144, 95% confidence interval 0.045-0.459; P=0.001). Conclusions:FVHs suggest that the blood supply is in a state of decompensation. When FVHs are present, the risk of cerebral infarction in patients with chronic middle cerebral artery occlusion is significantly increased; the wider the range of FVHs, the higher the risk of poor outcome after cerebral infarction.

Alzheimer's disease (AD) is one of the major diseases that harmful to healthy elderly, and mild cognitive impairment (MCI) is the early clinical stage of AD. There is a lag in the clinical diagnosis of both diseases. An objective and reliable auxiliary diagnostic method is urgently needed to provide early diagnosis and differential indicators for AD and MCI, to predict the probability of individuals suffering from AD and MCI transforming into AD, and to reduce the overall incidence of AD and reduce the huge medical and economic burden for the country and society. Event-related potential is widely used in AD and MCI, and the resolution at the millisecond level can truly reflect the time course of cognitive processing and the degree of impairment of cognitive function in patients. In this study, we investigated the differences in the amplitude and latency of ERP components in healthy elderly, MCI and AD patients, and the correlation between ERP components and cognitive impairment. Early N170 and P200 showed high sensitivity and specificity in differentiating MCI from healthy elderly or MCI from AD. The late perception-related ERPs also showed high sensitivity and specificity in differentiating healthy elderly from MCI/AD. The differences in ERPs between MCI and AD may be related to the etiology, the degree of disease progression and the site of brain damage. The specific brain mechanism still need to be further explored and will be the focus of future research. With the progress of the research, the relationship between the specific ERP manifestations and the mechanism of brain injury as well as the impairment of cognitive function will be more clear. It is believed that the application of ERP in clinical will bring more benefits to AD and its early clinical MCI.

Objective:To investigate the efficacy of different preferred thrombectomy strategies for embolic acute vertebrobasilar artery occlusion (AVBAO).Methods:Forty-four patients with embolic AVBAO who underwent endovascular treatment in Department of Neurology, Nanyang Central Hospital from January 2019 to June 2021 were included in the study. Patients were divided into stent-retriever thrombectomy group ( n=27) and aspiration thrombectomy group ( n=17) according to different preferred thrombectomy strategies. Modified Rankin scale (mRS) was used to evaluate the prognoses of these patients 90 d after surgery; the differences of clinical data, surgery-related characteristics, prognoses and complications between the two groups were compared. Results:There was no significant difference between the 2 groups in terms of time from onset to puncture, sites of target vessel occlusion, proportion of patients accepted intraoperative remedial measures, and successful recirculation rate of target vessels ( P>0.05). Compared with the aspiration thrombectomy group, the stent-retriever thrombectomy group had significantly decreased utilization rate of middle catheters, significantly increased retrieval attempts in thrombectomy, statistically lower re-recanalization rate of first-time thrombectomy on the target vessels, significantly longer time from puncture to re-recanalization, and significantly higher incidence of new embolism ( P<0.05). There was no significant difference between the 2 groups in incidences of vascular rupture and postoperative spontaneous intracerebral hemorrhage (sICH), and good prognosis rate 90 d after surgery ( P>0.05). Conclusion:For embolic AVBAO patients, similar recanalization and short-term good prognosis can be obtained by aspiration thrombectomy to those by stent-retriever thrombectomy; besides that, aspiration thrombectomy has advantages as shorter recanalization time, less new embolic complications and higher re-recanalization rate of first-time thrombectomy.