Objective To investigate the molecular mechanism of the effect of CYP2C19 polymorphism on the efficacy of clopidogrel in patients with stable coronary artery disease (SCAD).Methods A total of 208 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) were included.The CYP2C19 variant alleles were detected by gene sequencing.Platelet reactivity was assessed by thrombelastograph at 24 h after 300 mg clopidogrel loading.P2Y12-Gi signaling was measured by flow cytometric analysis of vasodilator-stimulated phosphorylation-platelet reactivity index (VASP-PRI) and Akt phosphorylation (P-Akt) index.Results Among 208 patients,40.9％ were classified as CYP2C19 * 1/* 1 (non-carriers) with no loss-of-function (LOF),44.7％ as CYP2C19 * 1/* 2 or CYP2C19 * 1/* 3 (one LOF carriers) and 14.4％ as CYP2C19 * 2/*2 or CYP2C19 * 2/* 3 (two LOF carriers).Both postclopidogrel platelet aggregation and VASP-PRI increased by the presence of one LOF allele,and were even more pronounced with the presence of two LOF alleles.In contrast,P-Akt index only increased in two LOF carriers.VASP-PRI was positively associated with postclopidogrel platelet aggregation (r =0.661,P＜0.001),but not with P-Akt index.Conclusions The two CYP2C19 LOF carriage was associated with more active state of P2Y12-Gi signaling in postclopidogrel platelet in Chinese patients with SCAD.

Objective:To compare the diagnostic value of strain ratio correction in ultrasound elasticity imaging and ultrasound-guided percutaneous biopsy for the diagnosis of breast imaging reporting and data system (BI-RADS) 4 breast mass. Methods:From January 2014 to June 2016 in the Affiliated Hospital of Chengde Medical College, 120 patients with breast tumor resection and preoperative BI-RADS4 of all the masses were included in this study. The diagnostic value of contrast ultrasound elastography strain ratio correction and biopsy in ultrasound-guided percutaneous biopsy was evaluated with pathology as the gold standard. Results:In the 120 cases of grade BI-RADS4 mass by ultrasound elastography after correction, 46 cases were graded BI-RADS4 without changing;59 cases were downgraded to BI-RADS3, and 15 cases were upgraded to BI-RADS5. The pathology, ultrasonic elastography strain ratio correction, biopsy diagnostic sensitivity, specificity, and accuracy were 90.7%, 81.8%, 85.5%, 88.8%, 98.5%, and 95.0%, respectively. A significant difference was found between ultrasonic elastography strain ratio correction and ultrasound-guided biopsy for the diagnosis of breast malignant mass (P<0.05), whereas no significant difference was found for the diagnosis of benign mass (P>0.05). Conclusion:Ultrasound-guided puncture biopsy is highly valuable in qualitative diagnosis of BI-RADS4 breast mass. After the pathological diagnosis, ultrasound elastography strain ratio has certain clinical value in BI-RADS4 guided biopsy and correction of mass classification.

Objective To investigate the prevalent feature of children with Mycoplasma pneumoniae (MP) infection in Xi'an region from Jan.2015 to Dec.2016.Methods From Jan.2015 to Dec.2016,9 648 cases with acute lower respiratory tract infection in xijing hospital were given serum test of the antibody of Mycoplasma pneumoniae by ELISA.Results A total of 9 648 cases with lower respiratory tract infection in children in xijing hospital received MP antibody detection,the positive cases were 2 971,the total positive rate was 30.79 ％.MP-IgM antibody positive rates between different age groups had significant differences,in which infants' group has the lowest(7.00 ％),and with the age growing,the positive rate increased.The positive rates in different age groups of toddler,preschool age,and school age were 27.29 ％,36.10 ％ and 37.76 ％ respec tively.The positive rates of MP-IgM antibody in different quarter were different.The highest antibody positive rate was found in the first quarter (January-March),followed by the fourth quarter,the third quarter and the second quarter.The difference was statistically significant (P＜0.01).Conclusion There was MP infection prevalence in Xi'an from 2015 to 2016.The positive rate in children increased with the age,the peak of infection was in the first quarter,so the detection and prevention of MP should be strengthened at that time of the year.

Objective:To understand the present situation of the construction of standardized asthma clinic for children in China, to explore the problems existing in the process of construction, and to promote the healthy development of standardized clinic construction.Methods:The process and current situation of the construction of standar-dized asthma clinics for children in China were reviewed and investigated, and the practical significance of the China Children′s Asthma Action Plan (CCAAP) in the construction of standardized asthma clinics for children was explored.Results:(1)By December 2020, 1 289 standardized asthma clinics for children and 135 regional demonstration centers had been built; 56 training sessions had been held, with a total of 2 560 doctors and 650 nurses trained, covering 2 560 hospitals across the country; and 4 518 patient education sessions were held.Online publicity covers a total of 1 million person-times, with an annual average of 1.33 million patients.(2)CCAAP improved the quality control level of standardized asthma clinic and promoted the standardized management of children.Conclusions:Through process optimization, professional evaluation, individual health education and real-time disease monitoring, standardized asthma clinic for children with asthma can effectively enhance asthma management awareness of children and their parents, improve disease awareness, and promote better control of asthma.It is an effective management model of asthma in children at present, and it is worthy of clinical promotion.CCAAP plays a good role in the construction of standardized outpatient clinic for asthma in children.The construction of standardized asthma clinic for children in China has achieved remarkable results, and the development trend is good in the future.

Objective:To investigate the effect of intercellular adhesion molecule-1 (ICAM1) targeted miR-133a-5p on lipopolysaccharide (LPS)-induced alveolar epithelial A549 cell injury.Methods:Dual lucife-rase reporter assay was used to verify the ICAM1 targeted effect of miR-133a-5p.A549 cells were induced by LPS in vitro and divided into the control group, LPS group, LPS+ negative control(miR-NC) group, LPS+ miR-133a-5p group, LPS+ small interfering RNA(si)-NC group, and LPS+ si-ICAM1 group.The expression levels of miR-133a-5p and ICAM1 mRNA were detected by real-time fluorescent quantitative PCR.Apoptosis was detected by flow cytometry.The expression levels of ICAM1, Bcl-2, Bax and cleaved caspase-3 protein that could activate cysteine were detected by Western blot.The expression levels of interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were detected by enzyme linked immunosorbent assay kit. Results:Compared with the control group, the LPS group had a decreased expression level of miR-133a-5p (0.39±0.04 vs.1.00±0.09) in A549 cells, increased expression of ICAM1 (0.86±0.08 vs.0.39±0.03), an increased apoptotic rate [(27.65±2.47)% vs.(8.13±0.89)%], and increased secretion of IL-6 [(624.59 ± 51.42) ng/L vs.(194.25±18.43) ng/L] and TNF-α [(548.35±51.42) ng/L vs.(174.26±19.43) ng/L]. The differences were significant (all P<0.05). Compared with the LPS+ miR-NC group, the apoptosis rate of A549 cells [(13.46±1.38)% vs.(28.71±2.54)%] in LPS+ miR-133a-5p group were significantly decreased, and the secretion of IL-6 [(296.43±23.51) ng/L vs.(635.86±55.41) ng/L] and TNF-α [(321.14±30.56) ng/L vs.(563.24±49.52) ng/L] was significantly decreased (all P<0.05). Compared with LPS+ si-NC group, the apoptosis rate of A549 cells [(13.65±1.64)% vs.(23.51±2.33)%] in LPS+ si-ICAM1 group was significantly decreased, and the secretion of IL-6 [(324.15±29.41) ng/L vs.(625.39±52.59) ng/L] and TNF-α [(334.65±20.46) ng/L vs.(534.97±51.42) ng/L] were significantly decreased (all P<0.05). Conclusions:miR-133a-5p can alleviate LPS-induced alveolar epithelial cell injury, and the mechanism may be related to down-regulation of ICAM1 expression.

Objective To investigate the association between heme oxygenase-1 (HO-1) gene rs2071746 polymorphism and long-term clinical outcome in patients with ischemic stroke.Methods Between July 2015 and June 2017,consecutive patients with acute ischemic stroke admitted to the Department of Neurology,the Third Affiliated Hospital of Soochow University were enrolled prospectively.TOAST classification was performed for all patients.Genotyping of the HO-1 gene rs2071746 polymorphism was performed using a modified multiplex ligase detection reaction technique.The patients were followed up.The primary endpoint events included ischemic stroke,vascular death,and myocardial infarction.Multivariate Cox proportional hazard regression model was used to analyze the independent influencing factors for primary endpoint events.Results A total of 1 698 patients with successful genotyping and follow-up information were enrolled.Genotyping showed that the frequency of rs2071746 A allelewas 44.91％.They were followed up for 15.21 ± 7.39 months,and 168 patients (9.89％) had primary endpoint events.The incidence of primary endpoint events in A allele carriers was significantly lower than that in non-A allele carriers (8.80％ vs.12.40％;P =0.018).Multivariate Cox proportional risk regression model showed that after adjusting for age,gender,hypertension,diabetes mellitus,smoking,alcohol consumption,and genotype,A allele was an independent protective factor for primary endpoint events in patients with acute ischemic stroke (hazard risk [HR] 0.693,95％ confidence interval [CI]0.506-0.949;P=0.022).Subgroup analysis showed that carrying the A allele was an independent protective factor for primary endpoint events in patients with large atherosclerotic stroke (HR 0.651,95％ CI 0.425-0.997;P=0.048),while rs2071746 polymorphism was not associated with long-term outcome in other etiological subtypes.Conclusion The HO-1 gene rs2071746 A allele may be a protective factor for the long-term outcome in patients with acute ischemic stroke and large atherosclerotic stroke.

Radiation protection drugs are often accompanied by toxicity, even amifostine, which has been the dominant radio-protecting drug for nearly 30 years. Furthermore, there is no therapeutic drug for radiation-induced intestinal injury (RIII). This paper intends to find a safe and effective radio-protecting ingredient from natural sources. The radio-protecting effect of Ecliptae Herba (EHE) was discovered preliminarily by antioxidant experiments and the mouse survival rate after ¹³⁷Cs irradiation. EHE components and blood substances in vivo were identified through UPLC‒Q-TOF. The correlation network of "natural components in EHE-constituents migrating to blood-targets-pathways" was established to predict the active components and pathways. The binding force between potential active components and targets was studied by molecular docking, and the mechanism was further analyzed by Western blotting, cellular thermal shift assay (CETSA), and ChIP. Additionally, the expression levels of Lgr5, Axin2, Ki67, lysozyme, caspase-3, caspase-8,8-OHdG, and p53 in the small intestine of mice were detected. It was found for the first time that EHE is active in radiation protection and that luteolin is the material basis of this protection. Luteolin is a promising candidate for RⅢ. Luteolin can inhibit the p53 signaling pathway and regulate the BAX/BCL2 ratio in the process of apoptosis. Luteolin could also regulate the expression of multitarget proteins related to the same cell cycle.

[This corrects the article DOI: 10.1016/j.apsb.2022.09.003.].

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques