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BACKGROUND@#Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.@*METHODS@#Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements.@*RESULTS@#Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.@*CONCLUSION@#PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Subject(s)
Rats , Male , Animals , Myocardial Reperfusion Injury/metabolism , Connexin 43/genetics , Sumoylation , Down-Regulation , Rats, Sprague-Dawley , Arrhythmias, Cardiac/drug therapy , Myocardial Ischemia/metabolism , RNA, Small Interfering/metabolismABSTRACT
Objective:To investigate the ability of predicting poor prognosis and the diagnosis efficacy of transcranial color Doppler ultrasound (TCCD) in acute ischemic stroke patients.Methods:A total of 264 AIS patients admitted to the Second Hospital of Dalian Medical University from January 2018 to March 2020 were selected and divided into early neurological deterioration (END) group (55 patients) and no END group (209 patients). The optic nerve sheath diameter (ONSD)/transverse eyeball diameter (ETD), middle cerebral artery pulsatility index (PI) and midline shift were detected by TCCD, and the results were analyzed.Results:The values of ONSD/ETD, PI and midline shift in the END group were higher than those in the no END group: 0.24 ± 0.02 vs. 0.22 ± 0.03, 1.26 ± 0.14 vs. 1.10 ± 0.12, (4.97 ± 1.13) mm vs. (3.41 ± 1.05) mm, and the differences were statistically significant ( P<0.05). The values of ONSD/ETD, PI, midline shift in the brain were positively correlated with the National Institutes of Health Stroke Scale (NIHSS) scores ( r1 = 0.531, r2 = 0.599, r3 = 0.566, all P<0.001). Multivariate analysis showed that NIHSS scores, blood glucose, ONSD/ETD, PI, brain midline shift values were related to END ( P<0.05). The prognostic area under the curve of the ONSD/ETD, PI, combined with brain midline shift values in assessing prognosis was 0.896, which was greater than any single index. The sensitivity was 84.62%, and the specificity was 89.08%. Conclusions:The detection of ONSD/ETD, PI and midline shift values by TCCD can provide important information for clinical assessment of the risk of END in AIS patients.
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Objective:To investigate the diagnostic value of rapid on-site evaluation (ROSE) technique in the mucosal biopsy under respiratory endoscopy in children with active tuberculosis.Methods:Clinical data of 40 patients with active tuberculosis diagnosed in Department of Respiratory Intervention, Qilu Children′s Hospital, Shandong University from June 2017 to January 2020 were retrospectively analyzed.Results:(1) There were 33 cases of tracheobronchial tuberculosis and 7 cases of tuberculous pleurisy in the 40 cases, among them 9 cases were difficult to diagnose.(2)Among 33 cases of tracheobronchial tuberculosis, 24 cases (72.7%) of caseous necrosis breaking into the lumen, and 9 cases (27.3%) of mucosal swelling and external pressure.Cytological ROSE (C-ROSE) showed granuloma, epithelioid cells and lymphocytic infiltration with all bronchial mucosal biopsies.Different positives results of microbiological ROSE (M-ROSE) in different biopsy parts: positive results were found 6 times at caseous necrosis (13.6%, 6/44 times), 4 times at granulation hyperplasia (12.5%, 4/32 times), 2 times at hyperemia and edema (22.2%, 2/18 times), 0 time at yellow-white necrosis, and 54 times at the junction between lesions and normal mucosa (81.8%, 54/66 times). The mucosal pathology showed granuloma, exudation and necrosis, including 22 cases with tuberculous granuloma, 5 cases with characteristic tuberculous nodules, and 11 cases with positive acid-fast staining.(3)Seven cases of tuberculous pleurisy, serious pleural adhesion, pleural hyperemia and edema were observed under thoracoscopy.After clearing the adhesive tape, scattered caseous miliary nodules were found in pleura in 4 cases with a difficult clinical diagnosis.The C-ROSE of smear on thoracoscopic biopsy were characterized by necrotic and histopathic cell, with multinucleated giant cells, but granuloma was rare.M-ROSE in different parts: 8 times positive for millet nodules (80.0%), 0 time positive for adhesion band, 2 times positive for congestion oedema (14.3%); biopsy pathology showed granuloma and necrosis, with 3 cases characteristic tuberculosis nodules and 2 cases positive for anti-acid staining.(4)Pathogenic microorganisms were detected in 19 children using next generation sequencing (NGS) and Mycobacterium tuberculosis/Rifampicin resistance real-time nucleic acid amplification detection technology (Xpert MTB/RIF), including 7 positive for NGS (36.8%), 8 positive (42.1%) and 5 positive for both NGS and Xpert MTB/RIF (26.3%).Conclusions:Respiratory endoscopy combined with ROSE technique has important clinical significance in early diagnosis of active tuberculosis in children, and it is worth of promotion and applying.
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Objective:To study the early predictors of Mycoplasma pneumoniae necrotizing pneumonia in children.Methods:Clinical data of 291 children with lobar pneumonia caused by Mycoplasma pneumoniae who were hospitalized in Department of Respiratory Intervention, Qilu Children′s Hospital of Shandong University from August 2016 to September 2018, were retrospectively analyzed.The patients were divided into necrotizing pneumonia group (154 cases) and non-necrotizing pneumonia group (137 cases). After comparing clinical characteristics, laboratory tests, and bronchoscopy findings, multivariate logistic regression analysis was carried out on the indicators with statistical significance to obtain the independent predictive indicators of Mycoplasma pneumoniae necrotizing pneumonia, and then the cutoff value with the maximum diagnostic value of each indicator was found through receiver operating characteristic (ROC) curve analysis.Results:There were no significant differences in gender and age distribution, duration before admission, and platelet count between the 2 groups(all P>0.05). Necrotizing pneumonia group manifested with 11.0(8.3-14.4)×10 9/L of white blood cell count, 0.740±0.115 of neutrophil, 44.2(21.2-72.0) mg/L of C-reactive protein(CRP), 55(35-80) mm/1 h of erythrocyte sedimentation rate, 0.19(0.08-0.60) ng/L of procalcitonin, 2.63(1.62-3.79) mg/L of plasma D-dimer, 456(340-665) U/L of serum lactate dehydrogenase, (35.6±4.3) g/L of serum albumin, 121 cases(78.6%)of bronchoscopic mucosal erosion, 75 cases(48.7%)of purulent lavage, 119 cases(77.3%)of massive secretions embolism; non-necrotizing pneumonia group manifested with 8.7(6.9-11.6)×10 9/L of white blood cell count, 0.660±0.127 of neutrophil percentage, 15.9(7.5-34.3) mg/L of CRP, 45(30-60) mm/1 h of erythrocyte sedimentation rate, 0.10(0.06-0.20) ng/L of procalcitonin, 0.69(0.46-1.24) mg/L of plasma D-dimer, 314(250-419) U/L of serum lactate dehydrogenase, (38.9±3.7) g/L of serum albumin, 53 cases(38.7%)of bronchoscopic mucosal erosion, 20 cases(14.6%)of purulent lavage, and 76 cases(55.5%)of massive secretions embolism.All the above indicators had statistical differences between the 2 groups.Erythrocyte sedimentation rate, serum lactate dehydrogenase, D-dimer, and bronchoscopic mucosal erosion were independent predictors of Mycoplasma necrotizing pneumonia.The area under the ROC curve were 0.643, 0.749, 0.858 and 0.699, respectively, with the cut off point of 53 mm/1 h, 335 U/L, and 1.36 mg/L, respectively. Conclusions:Erythrocyte sedimentation rate≥53 mm/1 h, serum lactate dehydrogenase≥335 U/L, D-dimer≥1.36 mg/L, and bronchoscopic mucosal erosion are early independent predictors of Mycoplasma necrotizing pneumonia in children, among which D-dimer has the highest value.
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Objective To analyze the gait kinematics parameters of patients with unilateral leg amputation after wearing prosthesis using the computer assisted rehabilitation environment (CAREN) gait assessment system,and the reasons for the differences.Methods Nine patients with unilateral mid-leg amputation were selected as the prosthesis group,and 11 healthy subjects were selected as the standard group.The gait kinematics parameters of the two groups were collected,processed and analyzed by using the CAREN gait evaluation system.Results The gait phase index of the prosthetic limb group was (0.88±0.04).Significant differences were observed between the prosthetic and healthy limbs in terms of step length,stance phase percentage,maximum hip extension angle and maximum knee flexion angle,maximum dorsiflexion and plantar flexion angle of the ankle joint during the stance phase,as well as the dorsiflexion angle of ankle joint during heel strike to the ground (P＜0.05).Moreover,there were significant differences between the affected limbs of the prosthetic limb group and limbs of the standard group in terms of the walking speed,gait cycle,stride length,percentage of stance phase,hip flexion angle,knee flexion and ankle dorsiflexion during heel strike,maximum hip extension and flexion angle,maximum dorsi-and plantar-flexion of ankle joint during stance phase (P＜0.05).Conclusion The relative symmetry of the gait of the unilateral leg amputee is (0.88±0.04),with their kinematics parameters of the prosthetic limb significantly weaker than those of the contralateral side and the healthy controls.
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Background and purpose:CpG methylation in promoter region is an essential mechanism for the dysfunction of the tumor suppression gene.Folate metabolism provides active methyl for organism methylation.Methionine synthase(MS) plays a vital role in the process of folate metabolism.This study aimed to explore the genetic polymorphism of MS, CHD5 methylation and their association with breast cancer morbidity.Methods:Fortyseven patients with primary breast cancer, 52 healthy subjects and 15 breast hyperplasia patients were enrolled in this experiment.The mRNA expression of CHD5 was determined by reverse transcription PCR(RT-PCR).Methylationspecific PCR(MSP) was used to detect the methylation status of CHD5.Polymorphisms in the MS gene were analyzed through the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Results:The mRNA expression of CHD5 in breast cancer tissues(0.27?0.19) and adjacent non-cancerous tissues(0.33?0.17) were both significantly lower than that in the breast hyperplasia tissues(0.67?0.14)(P