Background::Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods::Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.Results::A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04–13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65–3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38–1.53; P <0.001). Conclusions::In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration::ClinicalTrials.gov, NCT02309398.

Objective:To investigate the efficacy and feasibility of radiofrequency resection of supraglottic laryngeal carcinoma under a multifunctional opener.Methods:The clinical data of four cases of supraglottic laryngeal carcinoma (type T1N1M0 in two cases, T2N1M0 in one case, and T1N0M0 in one case) who received treatment in the Affiliated Hospital of Jining Medical University during January-June 2019 were retrospectively analyzed. Radiofrequency resection of supraglottic laryngeal carcinoma under a multi-functional opener combined with bilateral neck II-IV region lymph node dissection was performed. Swallowing, breathing and phonation were observed and analyzed based on references.Results:Among the four cases, two cases had a normal diet at 3 days after surgery, one case had a normal diet at 7 days after surgery, and one case had a normal diet at 16 days after surgery. Tracheotomy was not performed in any case. After surgery, breathing and speech communication were not affected.Conclusion:Radiofrequency surgery under a multifunctional opener can be used for treatment of early supraglottic laryngeal cancer. It is an effective treatment with minimal trauma, mild postoperative pain and promotes the early recovery of normal swallowing function.

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1β and tumor-necrosis factor-α in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.
Animals ; Computational Biology ; Constriction ; Down-Regulation ; Hyperalgesia ; Inflammation ; Injections, Spinal ; Mice ; MicroRNAs ; Neuralgia ; p38 Mitogen-Activated Protein Kinases ; Phosphotransferases ; Protein Kinases ; Rats ; Sciatic Nerve ; Spinal Cord ; Up-Regulation

Objective To investigate the effect of sodium arsenite (NaAsO2) on the expression of miRNA-21 (miR-21) mediated by transcription factor ETS-1 in human normal hepatocytes (L-02).Methods Dose-effect study:The L-02 cells were treated with different doses of NaAsO2 [0.0 (control),2.5,5.0,10.0,20.0,40.0 μmol/L] for 24 h.Time-effect study:L-02 cells were exposed to 0 (control) and 20 μmol/L NaAsO2 for 12,24,36 and 48 h (n =6).ETS-1 and miR-21 were treated with ETS-1 shRNA and miR-21 inhibitor,respectively.The cells treated with ETS-1 shRNA (100 nmol/L) were divided into 4 groups:①ETS-1 shRNA NC treatment alone (control group);②ETS-1 shRNA NC combined with NaAsO2 (20 μ,mol/L) treatment group;③ETS-1 shRNA treatment alone group;④Treatment with ETS-1 shRNA and NaAsO2 (20 μmol/L) group.The MiR-21 inhibitor (100 nmol/L) treated cells were also divided into 4 groups:① miR-21 inhibitor NC treatment (control group);② miR-21 inhibitor NC combined with NaAsO2 (20 μmol/L);③miR-21 inhibitor group;④miR-21 inhibitor combined with NaAsO2 (20 μ mol/L) treatment group.The expression of ETS-1 mRNA and miR-21 were detected by quantitative real-time PCR (qRT-PCR);the protein expression of ETS-1 was detected by Western blotting.Results Dose-effect study:The expression of ETS-1 mRNA in the groups of 0.0 (control),2.5,5.0,10.0,20.0 and 40.0 μmol/L was 1.008 ± 0.028,1.552 ± 0.029,1.697 ± 0.050,1.842 ± 0.077,2.233 ± 0.096 and 2.235 ± 0.092;miR-21 expression was 1.025 ± 0.094,1.552 ± 0.072,1.683 ± 0.066,1.915 ± 0.171,2.337 ± 0.195 and 2.592 ± 0.177;the expression of ETS-1 protein was 1.060 ± 0.045,1.267 ± 0.160,1.386 ± 0.087,1.723 ± 0.196,2.208 ± 0.122 and 2.284 ± 0.224,respectively,and the differences were statistically significant (F =47.797,8.959,65.748,all P ＜ 0.05),the NaAsO2 dose groups were significantly higher than those of the control group (all P ＜ 0.05),and there was a dose-effect relationship.Time-effect study:The expression of ETS-1 mRNA in L-02 cells was 1.253 ± 0.175,1.623 ± 0.220,1.771 ± 0.324 and 1.913 ± 0.251,respectively at 12,24,36 and 48 h;the expression of miR-21 was 1.502 ± 0.111,1.716 ± 0.113,1.979 ± 0.186 and 2.452 ± 0.304;the expression of ETS-1 protein was 1.196 ± 0.105,1.502 ± 0.076,1.651 ± 0.074 and 1.839 ± 0.139,respectively,there were significant differences between the groups (F =14.936,39.180,39.441,all P ＜ 0.05).The expression of various time points of exposure to NaAsO2 was significantly higher than those in the control group (1.044 ± 0.115,1.044 ± 0.124,1.108 ± 0.088,1.053 ± 0.061;1.092 ± 0.061,1.096 ± 0.169,1.024 ± 0.111,1.057 ± 0.146;1.020 ± 0.017,1.049 ± 0.121,1.024 ± 0.089,1.031 ± 0.124,all P＜ 0.05),and there was a time-effect relationship.ETS-1 shRNA and miR-21 inhibitor treatment:compared with ETS-1 shRNA NC combined with NaAsO2 (20 μmol/L),ETS-1 shRNA and NaAsO2 (20 μmol/L) could significantly inhibit the expression of ETS-1 (0.912 ± 0.238 vs 1.641 ± 0.225,P ＜ 0.05),and down-regulated the expression of miR-21 (1.313 ± 0.334 vs 2.363 ± 0.252,P ＜ 0.05).There was no significant difference of ETS-1 mRNA expression between miR-21 inhibitor and NaAsO2 (20.μmol/L) group (1.580 ± 0.077 vs 1.576 ± 0.065,P ＞ 0.05) compared with miR-21 inhibitor NC and NaAsO2 (20 μmol/L).Conclusions The expression of ETS-1 and miR-21 in L-02 cells is significantly higher than those in control.The high expression of ETS-1 mediates NaAsO2-induced miR-21 overexpression,which may be an important molecular mechanism of arsenic-induced expression dysregulation of human hepatic miRNAs and liver damage.

Objective Cryoballoon ablation of pulmonary vein (PV) ostia often induces a vagal response.This prospective study was designed to assess the effectiveness of prophylactic intravenous administration of atropine on hemodynamic impairment induced by cryoballoon ablation in patients with atrial fibrillation.Methods Twenty-five patients with paroxysmal atrial fibrillation undergoing cryoballoon ablation were prospectively enrolled and assigned to either the trial group on the control group.First twelve patients (the trial group) were administered 1 mg of atropine before deflation of the cryoballoon,while the following 13 patients (the control group) were given atropine only after the onset of the hemodynamic variation (decrease in heart rate and/or blood pressure).Treatment was considered effective when the hemodynamic variations were restored.Results In the trial group,three patients with transient hypotension did not require further supportive care throughout the procedures and one patient with hypotension required supportive management.In the control group,hypotension,bradycardia and mixed bradycardia with hypotension requiring supportive care occurred in six,three,and three patients,respectively.Overall,the rate of marked vagal responses was significantly lower when prophylactic atropine was administrated (4/12 vs.12/13 patients,P ＜ 0.01).Conclusions Atropine is effective in the prevention of all types of vasovagal responses induced by cryoballoon ablation in patients with atrial fibrillation.

Objective To investigate ablation characteristics of PVC/VT originating from left ventricle anterior papillary muscles.Methods This study included 10 patients of PVC/VT originating from left ventricle anterior papillary muscles from January 2015 to June 2016 in Beijing Anzhen Hospital.Electrophysiological mapping and radiofrequency ablation were completed using three-dimensional anatomical mapping system combined with three-dimensional intracardiac ultrasound technology.ECG and abaltion target diagram characteristics as well as the special anatomy were explored.Results All the 10 patients were successfully ablated and followed up for 12 months.One patient had recurrence within 12 months and no complications were recorded.The target sites localized at the tip (n =1),middle portion(n =4)or the base (n =5) of the LV-APM.Among 7 patients,the target sites were located at the anterior septal papillary muscle and in 3 patients were located in the free papillary muscle.9 patients were successfully ablated via anterograde trans-septal catheterization after the failure of retrograde approach.Premature QRS wave time were 152.80 ± 11.72 ms and 6 patients presented sharp potential at the targets during PVC/VT.Conclusions PVC/VT originating from left ventricle anterior papillary muscles have similar ECG and diagram characteristics that is different from which originating from left anterior fascicle.It is recommended to get the target via transseptalpuncure approach.Ablation target could be clearly positioned by three-dimensional intracardiac ultrasound technology.

Objective:To detect precancerous lesions of gastric cancer and biopsy tissue vascular endothelial growth factor (VEGF)and mutant p53 gene(mtp53)expression,to explore the development of clinical significance of VEGF and mutant p53 gene in gastric cancer.Methods:19 cases by endoscopic biopsies of normal gastric tissues,22 cases of intestinal metaplasia,47 cases of gastro-intestinal mucosal dysplasia, 54 cases of gastric cancer samples by immunohistochemical staining to detect the expression levels of VEGF and mtp53′s.Results: The expression levels of VEGF, mtp53 in normal gastric mucosa, intestinal metaplasia, dysplasia, and gradually increased gastric cancer was the law.mtp53 of VEGF expression in gastric carcinoma and compared with normal gastric tissue,intestinal metaplasia was significantly higher(P<0.05),but with atypical hyperplasia was no significant difference(P>0.05). Conclusion: The abnormal expression of VEGF and mutant p53 may be related to the degree of deterioration of the stomach tissue lesions related.

Objective To observe the change of histone acetylation homeostasis of the central cholinergic circuits in mice with post-stroke cognitive impairment (PSCI). Methods The male ICR mice were divided into sham group (n=60) and PSCI group (n=60). The middle cerebral artery occlusion (MCAO) model was established. The Morris water maze test was used to test the cognitive function, and the changes of function and the histone acetylation homeostasis of the central cholinergic circuits of unaffected side were detected by molec-ular biology methods. Results Compared with the sham group, the scores of Morris water maze test decreased in PSCI group (t>29.412, P<0.05); while the acetylcholine (Ach) level decreased (t>26.227, P<0.05), as well as the expression of choline acetyltransferase (ChAT) mRNA and protein (t>28.593, P<0.05), acetylated histone H3 (Ac-H3) (t>24.126, P<0.05), phosphorylated cAMP response element-binding protein (p-CREB) and CREB binding protein (CBP) (t>25.634, P<0.05), and the acetylated histone level of M promoter of ChAT (t>24.704, P<0.05). Conclusion Transient MCAO could cause PSCI. The function of the central cholinergic circuits was impaired, especially the his-tone acetylation homeostasis of the central cholinergic circuits, such as the acetylated histone level of ChAT promoter decreased. All of that might be related with the decline of p-CREB and CBP level in the corresponding brain regions induced by stroke.

Objective To observe the effects of an enriched environment (EE) on cognitive functioning and the synaptic plasticity of mice modeling post-stroke cognitive impairment (PSCI) and explore the possible mechanisms involved.Methods Mice modeling PSCI and sham-operated mice were randomly divided into 3 groups:sham-operated mice in a standard environment (the Sham+SE group),PSCI mice in a standard environment (the PSCI+SE group) and PSCI mice in an enriched environment (the PSCI+EE group).The cognitive functioning of all of the mice was quantified using a Morris water maze and their hippocampal long-term potentiation (LTP) was recorded using an electrophysiological method.The level of synaptophysin was detected using Western blotting.Synaptic ultrastructure in the hippocampus was imaged using electron microscopy.Results Compared with the Sham +SE group,the PSCI+SE group showed significantly poorer water maze performance and failed induction of contralateral LTP.Their average level of synaptophysin was significantly lower,and significant adverse changes in the synaptic ultrastructure of the hippocampus were observed,including a decreased number of synapses.The average width of the synaptic cleft,postsynaptic density and the interface curvature of the synapses were all less desirable.All of the measurements of the PSCI+EE group improved significantly compared to those of the PSCI+SE group,but were still significantly poorer than those of the Sham+SE group.Conclusions An enhanced environment can improve the cognitive functioning of mice modelling PSCI.It may be that an EE can improve synaptic plasticity in the hippocampus contralateral to the stroke.

Objective To investigate the clinical characteristics and prognosis of patients with different molecular subtypes of breast cancer.Methods A cohort of 716 breast cancer patients which had clear immunohistochemical detection were investiged.Their molecular subtypes were categorized as Luminal A,Luminal B,HER-2 over-expressing and basal-like subtypes,based on detection of ER,PR,HER-2 expression,and the clinical data including characteristics,relapse,prognosis and prognostic factors of the patients with different subtypes of breast cancer were analyzed retrospectively.Results There were no significant differences among different molecular subtypes at the age,menopausal status,production times,clinical stage,and radiation therapy(P ＞0.05).There were significant differences among different molecular subtypes at axillary lymph node starus (x2 =17.208,P =0.001),turner size (x2 =20.528,P =0.000) and operation method (x2 =24.242,P =0.000) and chemotherapy regimens (x2 =10.711,P =0.013).Univariate and multivariate analyses showed that clinical stage (x2 =17.005,P =0.002),axillary lymph node status (x2 =11.267,P =0.000) and molecular typing(x2 =125.634,P =0.000) were independent prognostic factors affecting long-term survisal rate.Conclusion Breast cancer patients in different subtypes have different long-term survival rate.The patients in basal-like subtype have the worst long-term survival rate.Molecular subtypes may provide important information to predict the prognosis of breast cancer.