Clinical Efficacy of Detailed Intervention After Clopidogrel Treatment and Analysis of Angina Relief in Patients with CHD.

Objective: Coronary heart disease is incurable and prone to recurrence, and long-term dependence on medication and good nursing management to improve the prognosis. The effect of clopidogrel in the treatment of coronary heart disease is affected by many factors, so paying more attention to details in the process of patient care is conducive to creating more ideal recovery conditions for patients. The purpose of this study is to conduct detailed intervention for coronary heart disease (CHD) after clopidogrel treatment, and to analyze the clinical efficacy of this intervention mode on CHD patients and the relief of angina pectoris. Methods: A total of 120 patients with coronary heart disease who were diagnosed and treated in our hospital from May 2020 to March 2022 were selected as the research objects and divided into a detail group (n=60) and a routine group (n=60) according to the computer randomization method, All research subjects were given clopidogrel intervention, followed by routine intervention in the routine group, and detailed intervention in the detail group. Detailed intervention includes specific measures such as psychological intervention, life intervention, health education, medical assessments, personalized care. The control of angina pectoris of the subjects was analyzed, and the daily life, motor function, quality of life score, negative emotion score and complications were observed. Results: The dimension score of TS [(83.50±5.14) points vs (77.42±4.35) points], DP [(85.59±5.78) points vs (80.14±5.43) points], PL [(79.62±5.19) points vs (74.18±5.04) points], AS [(90.69±6.35) points vs (85.57±6.12) points], AF[(83.54±5.22) points vs (77.51±5.16) points] in the detail group were higher than those of conventional group (P < .001). The differences in daily life, motor function of the subjects before the intervention were not comparable (P > .05), and the scores of daily life [(86.14±5.52) points vs (65.48±5.17) points] and motor function [(88.97±5.34) points vs (70.58±5.46) points] in the detail group at 4 weeks after intervention were higher than those in the routine group (P < .001). The quality of life in the detail group [mental state of (17.56±2.12) points vs (20.13±2.09) points, mental health of (15.62±2.34) points vs (18.09±2.06) points, social function of (15.86±2.41) points vs (18.11±2.14) points, emotional function of (14.36±3.45) points vs (16.78±3.69) points] were lower than those of the conventional group (P < .001). The negative mood scores [SAS score of (41.70±3.14) points vs (67.14±3.25) points, SDS score of (39.59±4.11) points vs (60.58±4.54) points] in the detail group were lower than those of the conventional group (P < .001). In addition, the total incidence of complications (3.33% vs 13.33%) in the detail group was significantly lower than that in the regular group (P < .001). Conclusions: Detailed intervention after clopidogrel treatment in CHD patients can significantly improve the efficacy of patients, reduce angina pectoris, and at the same time can effectively improve various physical functions and relieve their negative emotions, which is worthy of being widely used in clinical practice. Better control of angina pectoris is beneficial to reduce the frequency of hospital admission and save medical resources. The sample size of this study is small, and the sample size will be further expanded in the future to improve the scientific conclusion.

Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis.

The aim of our study is to disclose the role and underlying molecular mechanisms of circular RNA ubiquitin protein ligase E3 component n-recognin 4 (circ-UBR4) in atherosclerosis (AS). Our data showed that circ-UBR4 expression was upregulated in AS patients and oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) compared with healthy volunteer and untreated VSMCs. In addition, ox-LDL stimulated proliferation, migration, and inflammation but decreased apoptosis in VSMCs, which were overturned by the inhibition of circ-UBR4. miR-515-5p was sponged by circ-UBR4, and its inhibitor reversed the inhibitory effect of circ-UBR4 knockdown on proliferation, migration, and inflammation in ox-LDL-induced VSMCs. Insulin-like growth factor2 (IGF2) was a functional target of miR-515-5p, and overexpression of IGF2 reversed the suppressive effect of miR-515-5p on ox-LDL-stimulated VSMCs proliferation, migration, and inflammation. Collectively, circ-UBR4 knockdown decreased proliferation, migration, and inflammation but stimulated apoptosis in ox-LDL-induced VSMCs by targeting the miR-515-5p/IGF2 axis.

Brain network study of attentional cognitive impairment in children with bronchial asthma.

Bronchial asthma often causes cognitive impairment, especially attentional deficit, which has a serious impact on children's learning. This study aims to provide objective indicators for the evaluation of attention in asthma children. Thirty-one asthmatic and typically developing children (TDC) were tested by resting-state functional magnetic resonance imaging (rs-fMRI). Brain network-based methods of degree centricity and voxel-mirrored homotopic connectivity (VMHC) methods were used in the study. Compared with the TDC group, asthmatic children had lower DC values in the right superior frontal gyrus (after FDR correction, P < 0.05). Meanwhile, VMHC values of bilateral superior frontal gyrus and bilateral superior parietal lobule in asthmatic children were lower than those in TDC group (after FDR correction, P < 0.05). There was significant correlation between the correct percentage of CPT and DC value in right superior frontal gyrus, VMHC value in right superior frontal gyrus, and right superior parietal lobule. In this study, impaired superior frontal gyrus and parietal lobe function are associated with attentional deficit in asthmatic children, and these brain regions are key brain regions in attention-related networks.

Long-Circulation and Brain Targeted Isoliquiritigenin Micelle Nanoparticles: Formation, Characterization, Tissue Distribution, Pharmacokinetics and Effects for Ischemic Stroke.

Purpose: We designed a novel isoliquiritigenin (ISL) loaded micelle prepared with DSPE-PEG2000 as the drug carrier modified with the brain-targeting polypeptide angiopep-2 to improve the poor water solubility and low bioavailability of ISL for the treatment of acute ischemic stroke. Methods: Thin film evaporation was used to synthesize the ISL micelles (ISL-M) modified with angiopep-2 as the brain targeted ligands. The morphology of the micelles was observed by the TEM. The particle size and zeta potential were measured via the nanometer particle size analyzer. The drug loading, encapsulation and in vitro release rates of micelles were detected by the HPLC. The UPLC-ESI-MS/MS methods were used to measure the ISL concentrations of ISL in plasma and main tissues after intravenous administration, and compared the pharmacokinetics and tissue distributions between ISL and ISL-M. In the MCAO mice model, the protective effects of ISL and ISL-M were confirmed via the behavioral and molecular biology experiments. Results: The results showed that the drug loading of ISL-M was 7.63 ± 2.62%, the encapsulation efficiency was 68.17 ± 6.23%, the particle size was 40.87 ± 4.82 nm, and the zeta potential was -34.23 ± 3.35 mV. The in vitro release experiments showed that ISL-M had good sustained-release effect and pH sensitivity. Compared with ISL monomers, the ISL-M could significantly prolong the in vivo circulation time of ISL and enhance the accumulation in the brain tissues. The ISL-M could ameliorate the brain injury induced by the MCAO mice via inhibition of cellular autophagy and neuronal apoptosis. There were no the cellular structural damages and other adverse effects for ISL-M on the main tissues and organs. Conclusion: The ISL-M could serve as a promising and ideal drug candidate for the clinical application of ISL in the treatment of acute ischemic stroke.

Personalized warfarin treatment based on the PITX2 single nucleotide polymorphism rs6843082.

OBJECTIVE: To explore the effect of PITX2 gene rs6843082 single nucleotide polymorphism on the efficacy and adverse reactions of warfarin in patients with atrial fibrillation and hypertension, and to provide a theoretical basis for individualized warfarin treatment. METHODS: Data on 97 patients with atrial fibrillation and hypertension treated in our hospital were collected from September, 2018 to December, 2019. PCR and SNP genotyping techniques were used to measure the genotype at the rs6843082 locus (pituitary homeobox 2, PITX2) using DNA from the peripheral blood cells of all patients. We compared the efficacy of warfarin and the incidence of adverse reactions in patients of different genotypes. RESULTS: (1) Among 97 subjects, 58 cases (59.79%), 32 cases (32.99%) and 7 cases (7.22%) of PITX2 (rs6843082) genotypes GG, GA and AA were identified respectively. The G and A allele frequencies were 76.29% and 23.71%, respectively. (2) After all patients took warfarin to achieve the standard, the GA group and AA group's time to achieve the standard was significantly longer than that of the GG group (P<0.05). The difference was not statistically significant among groups (P>0.05). Compared with the GG group, the maintenance dose of the AA group was increased (P<0.05). (3) Compared with the GG and the GA group, the probability of bleeding events was higher in the AA group (P<0.05). (4) There was no difference in left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) group among GG, GA and AA groups (P>0.05). Compared with the GG group, left ventricular ejection fraction (LVEF) of the AA group was significantly reduced (P<0.05). (5) The mortality rates of the GG, GA, and AA groups were 15.51%, 12.50% and 22.57%, respectively, at the end of 120 d follow-up. CONCLUSION: Our findings show that rs6843082 SNP leads to the warfarin dose response differences that were observed in patients with atrial fibrillation and hypertension. Genotyping patients for rs6843082 before initiating warfarin treatment may optimize the treatment response and reduce bleeding incidence.

Metformin promotes proliferation and suppresses apoptosis in Ox-LDL stimulated macrophages by regulating the miR-34a/Bcl2 axis.

Background: Metformin, an antidiabetic drug, has been reported to be involved in atherosclerosis (AS). In this study, the effects of metformin on oxidized low-density lipoprotein (Ox-LDL)-induced macrophage apoptosis were investigated, and the mechanisms involved in this process were examined. Methods: qRT-qPCR analysis was performed to detect the expression of miR-34a in macrophage cells. Cell proliferation was determined by MTT assays and colony formation assays. Cell apoptosis was assessed by the detection of apoptotic rate and caspase 3 activity. Western blot analysis was performed to evaluate the expression of Bcl2 protein. Results: Metformin treatment promoted proliferation and suppressed apoptosis in macrophages following the treatment of oxidized low-density lipoprotein (Ox-LDL). Metformin could inhibit miR-34a in macrophages. miR-34a overexpression could reverse the effect of metformin on proliferation and apoptosis in Ox-LDL-treated macrophages. Moreover, metformin could increase the expression of the miR-34a target gene Bcl2. Furthermore, metformin treatment exerted the pro-proliferation and anti-apoptosis effect through regulating Bcl2 expression in Ox-LDL-stimulated macrophages. Conclusion: Metformin facilitated proliferation and inhibited apoptosis of macrophages treated with Ox-LDL through the miR-34a/Bcl2 axis, indicating the potential value of metformin in AS therapy.

Transport of active flavonoids, based on cytotoxicity and lipophilicity: an evaluation using the blood-brain barrier cell and Caco-2 cell models.

This in vitro study aims to evaluate and compare transmembrane transport of eight cardio-cerebrovascular protection flavonoids including puerarin, rutin, hesperidin, quercetin, genistein, kaempferol, apigenin and isoliquiritigenin via the rat blood-brain barrier cell and Caco-2 cell monolayer models, based on the data of cytotoxicity and lipophilicity. The cytotoxicity of the flavonoids to rat brain microvessel endothelial cell was determined by the MTT assay. The apparent permeability coefficients (Papp) of the flavonoids were calculated from the unilateral transport assays in Transwell system with simultaneous determination using a high performance liquid chromatography. The results showed that the cytotoxicity and oil-water partition coefficient of the flavonoids modified by the number and position of the glycoside and hydroxyl group were the key determinant for the transmembrane transport. The Papp values of the flavonoids reduced adversely when the numbers of glycoside and hydroxyl groups of the flavonoids increased accordingly. The tested flavonoids exhibited time-dependent Papp values in these models. The efflux mechanism related with P-glycoprotein also existed with the polar flavonoids; verapamil could enhance the permeation of rutin and quercetin via inhibition of P-glycoprotein. We propose that genistein and isoliquiritigenin with the permeation priority in vitro Caco-2 and BBB cell model could be better as the drug candidates for cardio-cerebral vascular protection. These findings provided important information for establishing the transport relationship for the flavonoid compounds and evaluating the potential oral bioavailability and brain distribution of the flavonoids.