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Background and Objectives@#Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs. @*Methods@#and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, RA signaling pathway was manipulated during the differentiation of hiPSC-CMs on day 5 post-differentiation, a crucial time point equivalent to the transition from cardiac mesoderm to cardiac progenitor cells in cardiac development. The resultant CMs were characterized at mRNA, protein and electrophysiology levels by a combination of qPCR, immunofluorescence, flow cytometry, and whole-cell patch clamp. The results showed that activation of the RA signaling pathway biased the differentiation of atrial CMs, whereas inhibition of the signaling pathway biased the differentiation of sinoatrial node-like cells (SANLCs). @*Conclusions@#Our study not only provides a novel and simple strategy to enrich SANLCs but also improves our under-standing of the importance of RA signaling in the differentiation of hiPSC-CMs.
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Objective:To investigate the clinical safety and efficacy of tirofiban in the treatment of hemiplegic stroke warning syndrome.Methods:Patients with hemiplegic stroke warning syndrome admitted to Jining First People's Hospital without receiving intravenous thrombolysis from January 2018 to May 2020 were enrolled retrospectively. Some patients were given tirofiban intravenous infusion for at least 24 h in acute phase, then received oral antiplatelet therapy (tirofiban group); some only received aspirin+ clopidogrel dual antiplatelet therapy (control group). The primary endpoint was muscle strength at the paralytic side and National Institutes of Health Stroke Scale (NIHSS) score at day 7 after onset. The secondary endpoint was the modified Rankin Scale (mRS) score at 3 months after onset, and ≤2 was defined as good clinical outcome. The safety endpoint was the bleeding events during treatment. Multivariate logistic regression analysis was used to determine the independent influencing factors of clinical outcome. Results:A total of 30 patients with hemiplegic stroke warning syndrome were enrolled, including 19 (63.3%) in the tirofiban group and 11 (36.7%) in the control group. There was no significant difference in baseline clinical data between the two groups, and no drug-related bleeding complications occurred during treatment. The muscle strength at paralytic side and NIHSS score at day 7 after onset, NIHSS score at discharge and good clinical outcome rate at 3 months in the tirofiban group were significantly better than those in the control group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that tirofiban was an independent protective factor for good outcome after adjusting the NIHSS score at the beginning of treatment (odds ratio 0.040, 95% confidence interval 0.040-0.449; P=0.009). Conclusions:Tirofiban is safe and effective in the treatment of patients with hemiplegic stroke warning syndrome in acute phase. It can effectively block the progress of the disease, improve the outcome of patients, and will not increase the risk of bleeding.
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Objective:To observe the effect of feedback pulmonary rehabilitation guidance on self-management of elderly patients with stable chronic obstructive pulmonary disease (COPD).Methods:Ninety-four elderly patients with stable COPD that visited the outpatient department between January 2018 and January 2019 were selected. Block randomization methods were used to divide the patients into two groups: routine lung rehabilitation instruction group (referred to as the “routine group”) and feedback lung rehabilitation group (referred to as the “feedback group”). The feedback group received the instruction of feedback pulmonary rehabilitation guidance, while the routine group received the instruction of routine pulmonary rehabilitation guidance. The quality of life and the self-management ability of the two groups before and after the intervention were compared.Results:There was no statistically significant difference between the scores of the feedback and routine groups before the intervention of the COPD-specific self-management scale ( P>0.05). In the feedback group, the scores of emotional management, daily life management, symptom management, self-efficacy management, and information management on the COPD-specific self-management scale after the intervention were 45.01±5.31, 53.10±6.60, 25.88±3.03, 35.01±5.31, and 24.32±4.20, respectively, whereas those for the routine group were 40.23±5.19, 48.02±6.58, 22.88±3.01, 31.01±4.80, and 20.30±2.88, respectively. The scores of the feedback group were higher than the routine group and the difference was significant ( P<0.001). There was no significant difference between the feedback group and the routine group before the intervention of the respiratory disease questionnaire, i.e., the airways questionnaire 20-revised (AQ20-R) score ( P>0.05). The AQ20-R score of the feedback group after the intervention was 7.22±1.08, which was lower than that of the routine group (9.01±2.01); the difference was significant ( P<0.001). Conclusion:The application of feedback pulmonary rehabilitation guidance in the self-management of elderly patients with stable COPD can improve both their self-management ability and quality of life.
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Objective:To investigate the safety of intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel in patients with unruptured intracranial aneurysms accepted stent-assisted coil embolization, and explore the effect of tirofiban on perioperative thrombotic events.Methods:The clinical data of 275 patients with unruptured intracranial aneurysms who underwent stent assisted coil embolization in our hospital from January 2016 to December 2019 were retrospectively collected. Among them, 110 patients admitted to our hospital from January 2016 to December 2017 only received preoperative oral administration of aspirin and clopidogrel combined with antiplatelet treatment (classic group), and 165 patients admitted to out hospital from January 2018 to December 2019 received intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel (improved group). The differences of perioperative safety and thrombotic events between the two groups were compared and analyzed.Results:The incidence of intraoperative visual thrombotic events in the classic group and the improved group were 6.4% (7/110) and 1.2% (2/165), respectively, with significant difference ( P<0.05); the incidence of postoperative thrombotic events was 4.5% (5/110) and 2.4% (4/165), respectively, without significant difference ( P>0.05); the incidence of urethrorrhagia was 9.1% (10/110) and 21.2% (35/165), respectively, with significant difference ( P<0.05); and the incidence of gingival hemorrhage was 13.6% (15/110) and 19.4% (32/165), respectively, without significant difference ( P>0.05). No acute gastrointestinal hemorrhage or cerebral hemorrhage occurred in both groups; urethrorrhagia and gingival hemorrhage were transient and relieved spontaneously. Conclusion:Intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel can reduce the incidence of intraoperative visual thrombotic events without increasing the risk of hemorrhage in stent-assisted coil embolization of unruptured intracranial aneurysms.
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Objective To investigate the effect of neurotrophin-3(NT-3)on the proliferation and apoptosis of bone marrow mesenchymal stem cells(BMSCs)in rats and possible mechanisms. Methods The NT-3 overexpression and lentiviral transfection of BMSCs were co-cultured with neuronal cells respectively and then they were divided into overexpression control group,NT-3 transfection group and shRNA-NT-3 transfection group(NT-3 silencing group).MTT assay was used to detect the cell culture for 24 h,48 h and 72 h. Cell cycle and apoptosis were detected by flow cytometry for 48 h. Real-time quantitative PCR was used to detect the expression of C/EBPβmRNA.The expression of C/EBPβprotein was detected by Western blot. Results MTT results showed that the proliferation ability of BMSCs in the NT-3 overexpres-sion group was significantly higher than that in the control group(0.650±0.042,0.826±0.074)at 48 h and 72 h(P<0.05).Compared with the control group(P<0.05),the cell cycle and apoptosis of BMSCs in NT-3 silencing group were significantly decreased at 48 h and 72 h(P<0.05). The results of 48 h cell cycle and apoptosis showed that the percentage of G1 phase in BMSCs was decreased,G2 and S were increased and the apoptosis was decreased. The percentage of G1 phase in G2-S phase and the increase of apoptosis were in-creased in NT-3 silencing group. The results of Western Blot showed that C/EBPβ mRNA and protein levels were significantly up-regulated in BMSCs of NT-3 overexpression group and significantly decreased in NT-3 silencing group(P<0.05).Conclusion NT-3 may promote the expression of C/EBP beta and affect the ex-pression of its downstream target genes,which can inhibit the apoptosis of BMSCs cells.
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Objective To observe the significance of rehabilitation integrated system for stroke patients. Methods From October, 2013 to June, 2015, 95 stroke patients were divided randomly into experimental group (n=48) and control group (n=47). The experimental group received rehabilitation under the guide of rehabilitation integrated system, while the control group in the routine process. They were assessed with simplified Fugl-Meyer Assessment (FMA) and Barthel Index (BI) before and 3 months after treatment. The satisfaction was also inves-tigated. Results There was no significant difference between groups in the differences of scores of FMA and BI before and after treatment (t0.05), while the satisfaction was higher in the experimental group (t=4.287, P<0.01). Conclusion The application of rehabilitation integrated system may improve the process of treatment and the efficiency of management, and result in more satisfaction of the stroke pa-tients.
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Objective To investigate the correhtion between cognitive impairment and cerebral atherosclerosis in patients with acute ischemic stroke.Methods Acute ischemic stroke patients without cognitive impairment were recruited before symptom onset.The Montreal cognitive assessment (MoCA) was used to evaluate the cognitive function.Magnetic resonance imaging (MRI) was used to identify the infarct locations and sides.Magnetic resonance angiography,CT angiography and digital subtraction angiography were used to identify atherosclerotic arteries.Resul~ A total of 101 patients with acute ischemic stroke were enrolled,including 75 (74.3％) with cognitive impairment.The proportions of age (54.54 ± 12.59 years vs.64.43 ± 10.37 years;t =-3.960,P ＜0.001),years of education ≤6 years (50.7％ vs.11.5％;x2 =12.257,P ＜ 0.001),and cerebral atherosclerosis (89.3％ vs.50.0％;x2 =18.137,P ＜0.001) of the cognitive impairment group were significantly higher than those of the normal cognitive function group.Multivariate logistic regression analysis showed that cerebral atherosclerosis was an independent risk factor for cognitive impairment in patients with acute ischemic stroke (odds ratio 1.720,95％ confidence interval 1.005-2.942;P=0.048).MoCA score was negatively correlated with the offending vessels (r=-0.365,P＜ 0.001) and the most severe vessels of atherosclerotic degree (r=-0.243,P =0.014).Conclusions Most patients with acute ischemic stroke had cognitive impairment in the early stage after onset,and the MoCA scores was negatively correlated with the degree of cerebral atherosclerosis.Cerebral atherosclerosis was an independent risk factor for cognitive impairment in patientswith acute ischemic stroke.
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Objective To research the correlation on high performance liquid chromatography (HPLC) and antidepressant effect of different elution fractions of acorus tatarinowii schott macroporous resin .Methods Prepared different fractions by using AB‐8 macroporous resin .Establish HPLC characteristic chromatograms of crude drugs and different elution fractions from AB‐8 acorus tatarinowii schott macroporous resin by using gradient elusion .Confirm characteristic peaks in chromatograms .despair mod‐els of male mice ,including tails suspension test (TST ) ,forced swimming test (FST ) were used to evaluate antidepressant effects by taking orally .Results HPLC chromatograms of crude drugs and different fraction of acorus tatarinowii schott showed that they had same characteristic peaks .Elution of 90% and 70% alcohol solution from AB‐8 macroporous resin can obviously reduce TST and FST time .The anti‐depressant effect were associated with characteristic peaks on chromatogram .Conclusion Acorus tatarinowii schott has anti‐depressant effect ,and mainly from 70% and 90% alcohol solution eluted from AB‐8 macroporous resin .HPLC char‐acteristic chromatography and data relationship between relative peaks can be used to judge the antidepressant effects of acorus ta‐tarinowii schott ,and give reference to research and product development .
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Carotid stenosis is one of the important risk factors for cerebrovascular disease.Many studies have shown that carotid stenosis may cause cognitive impairment,but the specific mechanisms remain unclear.Carotid endarterectomy and stenting can relieve carotid stenosis,improve cerebral perfusion,and may improve the cognitive function of patients,but the complications and long-term efficacy after intervention remain to be further studied.