Association between post-stroke smoking and stroke recurrence in first-ever ischemic stroke survivors: based on a 10-year prospective cohort.

BACKGROUND: Whether smoking is a risk factor for ischemic stroke (IS) recurrence in IS survivors is still uncovered, and evidences are sparse. Meanwhile, an add-on effect of clopidogrel was observed in myocardial infarction patients who smoked, but whether the paradox exists in IS patients is still unsolved. The objectives of this study are to explore the association between smoking behavior after index stroke and IS recurrence and to explore whether the paradox exists. METHODS: A prospective cohort of first-ever IS patients was conducted between 2010 and 2019. The prognosis and smoking features of enrolled patients were obtained via telephone follow-up every 3 months. Fine-gray model with interaction terms was applied to measure the relationships between stroke recurrence and smoking behaviors after index stroke and to explore the add-on effect of clopidogrel in smoking patients. RESULTS: There were 171 (24.26%) recurrences and 129 (18.30%) deaths during follow-up in 705 enrolled IS patients. One hundred forty-six (20.71%) patients smoked after index stroke. The hazard ratios (HRs) and 95% confidence intervals (CIs) of interaction terms between antiplatelet drug and follow-up smoking (smoking status and daily smoking amount) were 1.092 (95% CI: 0.524, 2.276) and 0.985 (95% CI: 0.941, 1.031), respectively. A significantly higher risk of recurrence was observed in patients with a higher daily smoking amount during follow-up (per cigarette), with HR being 1.027 (95% CI: 1.003, 1.052). CONCLUSIONS: Smoking could elevate the risk of IS recurrence, and IS survivor should be advised to quit or smoke less. Add-on effect of clopidogrel may not exist in smoking strokers taking clopidogrel.

Associations between Lesion Locations and Stroke Recurrence in Survivors of First-ever Ischemic Stroke: A Prospective Cohort Study.

Several studies have indicated that stroke survivors with multiple lesions or with larger lesion volumes have a higher risk of stroke recurrence. However, the relationship between lesion locations and stroke recurrence is unclear. We conducted a prospective cohort study of first-ever ischemic stroke survivors who were consecutively enrolled from January 2010 to December 2015. Stroke recurrence was assessed every 3 months after post-discharge via telephone interviews by trained interviewers. Lesion locations were obtained from hospital-based MRI or CT scans and classified using two classification systems that were based on cerebral hemisphere or vascular territory and brain anatomical structures. Flexible parametric survival models using the proportional hazards scale (PH model) were used to analyze the time-to-event data. Among 633 survivors, 63.51% (n=402) had anterior circulation ischemia (ACI), and more than half of all ACIs occurred in the subcortex. After a median follow-up of 2.5 years, 117 (18.48%) survivors developed a recurrent stroke. The results of the multivariate PH model showed that survivors with non-brain lesions were at higher risk of recurrence than those with right-side lesions (HR, 2.79; 95%CI, 1.53, 5.08; P=0.001). There was no increase in risk among survivors with left-side lesions (HR, 0.97; 95%CI, 0.53, 1.75; P=0.914) or both-side lesions (HR, 1.24; 95%CI, 0.75, 2.07; P=0.401) compared to those with right-side lesions. Additionally, there were no associations between stroke recurrence and lesion locations that were classified based on vascular territory and brain anatomical structures. It was concluded that first-ever ischemic stroke survivors with non-brain lesion had higher recurrence risk than those with right-side lesion, although no significant associations were found when the lesion locations were classified by vascular territory and brain anatomical structures.

Stereoselective Assembly of Multifunctional Spirocyclohexene Pyrazolones That Induce Autophagy-Dependent Apoptosis in Colorectal Cancer Cells.

Enantio- and diastereoselective synthesis of multifunctional spiropyrazolone scaffolds has been achieved using secondary amine-catalyzed [4 + 2] annulations of α,ß,γ,δ-unsaturated pyrazolones with aldehydes. The pyrazolone substrates serve as C4 synthons to produce 6-membered, carbocycle-based, chiral spiropyrazolone derivatives. The synthesized chiral compounds showed potent toxicity against a panel of cancer cell lines. The most potent compound 3h-induced cell cycle arrest and macroautophagy in HCT116 colorectal cancer cells, triggering autophagy-dependent apoptotic cell death.

[Altered Functional Connectivity in Patients with Transient Ischemic Attack by Resting-state Functional MRI].

OBJECTIVE: To investigate longitudinal changes in functional connectivity during resting-state in patients with transient ischemic attack (TIA). METHODS: 35 patients first suffering TIA in the right hemisphere were recruited, with 35 healthy volunteers were recruited as control. At 1 week and 3 months after TIA attack, functional magnetic resonance imaging (fMRI) scans were performed, then resting-state functional connectivity was assessed and compared with that of healthy subjects. Right inferior prefrontal cortex (iPFC) and its mirror region was used as region of interest (ROI) in this analysis. RESULTS: Compared with controls, higher functional connectivity with the left cerebellum, right superior temporal gyrus (STG) and insula, and lower functional connectivity with the right middle frontal gyrus (MFG) was demonstrated in patients at 1 week after TIA; while decreased functional connectivity in right STG, left insula and bilateral thalamus was shown in patients at 3 month after TIA. Correlation analysis found that functional connectivity of right iPFC with the cerebellum and insula was positively correlated with 2-back reaction time at 1 week after TIA. CONCLUSION: Although the nervous system signs of TIA can be quickly recovered, abnormal activation of working memory-related brain regions will occur for a long time.

Differences in brain-derived neurotrophic factor gene polymorphisms between acute ischemic stroke patients and healthy controls in the Han population of southwest China.

Single-nucleotide polymorphisms in the brain-derived neurotrophic factor gene may affect the secretion and function of brain-derived neurotrophic factor, thereby affecting the occurrence, severity and prognosis of ischemic stroke. This case-control study included 778 patients (475 males and 303 females, mean age of 64.0 ± 12.6 years) in the acute phase of ischemic stroke and 865 control subjects (438 males and 427 females, mean age of 51.7 ± 14.7 years) from the Department of Neurology, West China Hospital, Sichuan University, China between September 2011 and December 2014. The patients' severities of neurological deficits in the acute phase were assessed using the National Institutes of Health Stroke Scale immediately after admission to hospital. The ischemic stroke patients were divided into different subtypes according to the Trial of Org 10172 in Acute Stroke Treatment classification. Early prognosis was evaluated using the Modified Rankin Scale when the patients were discharged. Genomic DNA was extracted from peripheral blood of participants. Genotyping of rs7124442 and rs6265 was performed using Kompetitive Allele Specific polymerase chain reaction genotyping technology. Our results demonstrated that patients who carried the C allele of the rs7124442 locus had a lower risk of poor prognosis than the T allele carriers (odds ratio [OR] = 0.67; 95% confidence interval [CI]: 0.45-1.00; P = 0.048). The patients with the CC or TC genotype also exhibited lower risk than TT carriers (OR = 0.65; 95% CI: 0.42-1.00; P = 0.049). The AA genotype at the rs6265 locus was associated with the occurrence of ischemic stroke in patients with large-artery atherosclerosis (OR = 0.58; 95% CI: 0.37-0.90; P = 0.015). We found that the C allele (CC and TC genotypes) at the rs7124442 locus may be protective for the prognosis of ischemic stroke. The AA genotype at the rs6265 locus is likely a protective factor against the occurrence of ischemic stroke in patients with large-artery atherosclerosis. The study protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval ID number 2008[4]) on July 25, 2008.

[Relative Survival of Patients with Ischemic Stroke].

OBJECTIVE: To estimate the relative survival ratio of patients with ischemic stroke and its risk factors. METHODS: Lifetable and Ederer Ⅱ methods were used to estimate the relative survival ratio of patients with ischemic stroke. The Poission error structure model was adopted to determine the risk factors associated with survival. RESULTS: The patients had 99%, 98%, 98% and 99% relative survival ratio 1 year, 3 years, 5 years and 7 years after stroke, respectively. The relative excess risk of death increased with age [53-62 yr. vs. <53 yr., relative excess risk (RER=26.975, 95%CI: 1.668-410.90, P=0.020 1], higher mRS scores (≥3 vs. <3 points, RER=14.700, 95%CI: 1.05-206.45, P=0.047 3), and under body mass (vs. normal body mass, RER=10.082, 95%CI: 2.076-48.958, P=0.004 2). CONCLUSION: Ischemic stroke patients have a good prognosis, with slightly lower survival rates than the matched general populations. Those who are older, under body mass, and have a higher mRS score have lower survival rates.

Long-term trends and predictors of smoking behaviors among men following first-ever ischemic stroke.

Continued smoking following stroke is associated with adverse outcomes including increased risk of mortality and secondary stroke. The aim of this study was to examine the long-term trends in smoking behaviors and factors associated with smoking relapse among men who survived their first-ever stroke. Data collection for this longitudinal study was conducted at baseline through face-to-face interviews and follow-up was completed every 3 months via telephone, beginning in 2010 and continuing through 2014. Cox proportional hazard regression models were used to identify predictors of smoking relapse behavior. At baseline, 372 male patients were recruited into the study. Totally, 155 (41.7%) of these patients stopped smoking for stroke, and 61 (39.3%) began smoking again within 57 months after discharge with an increasing trend in the number of cigarettes smoked per day. Exposure to environmental tobacco smoke at places outside of home and work (such as bars, restaurants) (HR, 2.34; 95% CI, 1.04-5.29, P=0.04), not having a spouse (HR, 0.12; 95% CI, 0.04-0.36; P=0.0002) and smoking at least 20 cigarettes per day before stroke (HR, 2.42; 95% CI, 1.14-5.14, P=0.02) were predictors of smoking relapse. It was concluded that environmental tobacco smoke is an important determinant of smoking relapse among men who survive their first stroke. Environmental tobacco smoke should be addressed by smoke-free policies in public places.

[Clinical characteristics and prognosis of patients with cerebral venous sinus thrombosis in southwest China].

OBJECTIVE: Cerebral venous sinus thrombosis (CVST) is a rare cerebral vascular disease. Early diagnosis and treatments are crucial for a better prognosis. This study investigated the clinical characteristics and risk factors associated with the prognosis of patients with CyST. METHODS: From Jan 2009 to Jan 2013, patients who were admitted to the Department of Neurology of West China Hospital with confirmed CVST (according to the 2006 guideline of European neurology with neuroimaging when necessary) were consecutively recruited. Their medical records including demographic information and detailed clinical data were analyzed. The functional outcome of CVST was assessed 12 months after discharge using the modified Rankin Scale (mRS). RESULTS: A total of 73 patients were enrolled in this study. Acute and chronic onset of illness accounted for 13.7% and 35.6% of all patients, respectively. The earliest common symptom was headache (90.4%). Other initial symptoms included decreased visual acuity or blurred vision (2.7%), unilateral limb weakness (2.7%), diplopia (1. 4 9/o) and seizure (1.4%). CT scan was conducted in 46 patients (63.3%), which revealed 8 (17.4%) cases of cerebial hemorrhagic infarction. Delta sign and cord sign was shown in 34.8% and 30.4% CT imaging, respectively. The MRI scan confirmed that 27. 5% of those patients had encephaledema, 55% had delta sign and 45% had cord sign. The commonly involved location of CVST was right lateral sinus (68.5%), left lateral sinus (57.5%), ongitudinal sinus (53. 4%), left sigmoid sinus (50.7%), right sigmoid sinus (47.8%), confluence sinuum (32.9%), nferior sagittal sinus (21.900), sinus rectus (20.5%), jugular vein (12. 3%) and cerebral vein (9.6%). During the 12-month follow-up, 6.8% patients died, 72.6% had good mRS outcome (<2) and 27.4% had poor mRS outcome (> OR =2). The regression analysis identified epilepsy and papilledma as independent predictors of poor prognosis of CyST. CONCLUSION: It is difficult to recognize CVST at an early stage due to its diverse clinical presentations. Neuroimaging may be helpful for the diagnosis. Epilepsy and papilledema are potentially independent predictors for the 12-month functional outcome of patients with CVST.

[Effect of hyaluronic acid on promoting bone marrow-derived mesenchymal stem cells to differentiate into neural cells in vitro].

OBJECTIVE: To determine the effect of hyaluronic acid (HA) on promoting bone marrow-derived mesenchymal stem cells (BMSCs) to differentiate into neural cells. METHODS: BMSCs were purified and monitored. NSE+/NF+ cells and nestin+ cells were detected by immunocytochemistry. The mRNA levels of NSE, NF and nestin were determined by RT-PCR. RESULTS: The BMSCs adhered to HA hydrogel, with many surface projections, branches or crossing (Group A). Those cultured in brain tissue culture medium grew projections with fewer branches (Group B). Group A had more NSE+ cells (92.58 +/- 15.84) than Group B (80.26 +/- 16.47), and more NF+ cells (71.25 +/- 17.44) than Group B (52.37 +/- 14.75) (P < 0.05). At day 2 post-stimulation, more nestin+ cells were found in Group A (48.3 +/- 7.7) compared with Group B (34.6 +/- 5.2) (P < 0.05). At day 7, the mRNA levels of NSE and NF increased in both groups, but more in Group A. Nestin mRNA increased at day 2 post-stimulation and dropped at day 7 in both groups, where more significant in Group A. CONCLUSION: HA hydrogel provides structural support and proper microenvironment for the growth, proliferation and differentiation of BMSCs, and promotes BMSCs to differentiate into neuron cells.

The functional SNP rs4376531 in the ARHGEF gene is a risk factor for the atherothrombotic stroke in Han Chinese.

The gene encoding RhoA guanine nucleotide exchange factor 10(ARHGEF10) has been reported to be a risk factor for atherothrombotic stroke (AS) in Japanese. The single-nucleotide polymorphism (SNP) rs4376531 in intron 16 on ARHGEF10 is associated with AS and may play a role in the disease pathology. In order to explore the nature of this association in greater detail and in a new ethnic group, we carried out a case-control study to determine whether the rs4376531 polymorphism in ARHGEF10 is a risk factor of AS in Han Chinese people. This study was carried out to assay the frequency of genotypes and alleles of SNP rs4376531 in ARHGEF10 in patients with ischemic stroke and healthy controls using the polymerase chain reaction and the restriction fragment length polymorphism (PCR-RFLP) technique. A total of 383 individuals with AS in West China Hospital and 214 unrelated healthy controls were recruited. The frequencies of the G allele and GG genotype of the rs4376531 polymorphism were higher in the patients with AS than in control individuals: frequency of G, 91.0% vs 83.4%, P<0.001; GG, 82.2% vs 67.8%, P<0.001. After adjusting for sex, age, and multiple cardiovascular risk factors, the homozygous GG genotype for this variant was associated with a higher risk of AS, with an adjusted odds ratio of 4.99 (95% CI, 2.55-7.81, P< 0.001). Our findings suggest that the rs4376531 polymorphism in the ARHGEF10 gene is a risk factor for AS in the Han Chinese population.