Objective To investigate the efficacy of permanent left ventricular epicardial pacing through left lateral thoracotomy in children with complete atrioventricular block (CAVB)or complete left bundle branch block (CLBBB)as well as its effects on heart synchronization.Methods Permanent left ventricular epicardial pacemakers were implanted through left lateral thoracotomy in 26 children with CAVB or CLBBB in Heart Center,the First Affiliated Hospital of Tsinghua University.These children aged (2.3 ±2.1 )years old (1 month -9 years old),weight (1 1 .2 ± 5.8)kg (5 -32 kg),among them 1 5 cases were male and 1 1 cases were female.Among the 26 patients,24 patients had CAVB and 2 patients had dilated cardiomyopathy secondary to CLBBB.Fifteen children who visited the Pediatrics Department for acute upper respiratory tract infection were chosen as control group.The efficacy of left ventricular epi-cardial pacemakers was analyzed and its effects on heart synchronization were observed by using tissue Doppler imaging (TDI).Results Implantations of pacemakers were successfully conducted in all the 26 patients with no complications associated with operations.Left atrial and ventricular dual chamber epicardial pacemakers were implanted in 21 patients and left ventricular single chamber epicardial pacemakers were implanted in 5 patients.Within the follow -up period of (28.2 ±1 5.1 )months (1 month -51 months),atrial and ventricular leads were 1 00% effective.No significant diffe-rence was found in atrial electrode sensing,ventricular electrode threshold and ventricular electrode impedance com-pared with those during implantation(P >0.05).For the 6 patients with preoperative cardiac insufficiency,their left ventricular diastolic diameters decreased from (48.50 ±1 1 .1 0)mm to (40.67 ±6.40)mm after operation,and the difference was significant (t =2.96,P =0.030);but left ventricular ejection fraction increased from 0.27 ±0.08 to 0.53 ±0.08 after operation,and the difference was significant (t =-5.02,P =0.004).Two patients with right ven-tricular pacing developed pacemaker syndrome and were switched to left ventricular epicardial pacing.Their cardiac function returned to normal 1 .5 and 2.0 years later,respectively.Fifteen patients received evaluation of heart synchroni-zation by TDI.No significant difference was found in LVEF,septal -to -lateral wall motion delay,septal -to -posterior wall motion delay and standard deviation of Standard deviation of the peak tissue velocity between these 2 groups(all P >0.05).Conclusions For children requiring epicardial pacing,left ventricular epicardial pacing is safe and effec-tive,which can protect left ventricular systolic synchronization,prevent or reverse the pacemaker syndrome.

Objective:To observe the expression level of β-arrestin 1/2 in mice with Parkinson's disease(PD)and its relationship with pathogenesis of PD.Methods:PD model was prepared by using 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride(MPTP). The mice were killed at 3 days after the last administration and the brain tissue was taken for observing brain histopathological changes.The colocalization of β-arrestin1/2 with microglia was detected by using immunofluorescence double-labeling of β-arrestin1/2 and microglia.Tyrosine hydroxylase(TH)and Iba-1 were used to label cells, and then the loss of dopaminergic neurons and the activation of microglia were observed by immunohistochemistry.Results:As compared with the blank control group, the relative expression level of β-arrestin1 protein in brain tissue of PD mice was increased significantly, while the relative expression level of β-arrestin2 protein was decreased significantly( t=11.535, 9.948, both P=0.000), and β-arrestin1/2 shared cell localization with microglia.After MPTP induced PD, the number of Th + neurons in SNc area of midbrain was decreased significantly in β-arrestin1 + /+ group and β-arrestin1 -/- group( t=4.098, 3.571, P=0.000, 0.001), while the number of Iba-1 + cells in SNc area of midbrain was increased significantly( t=10.097、6.448, both P=0.000). After MPTP induced PD, the number of Th + neurons in SNc area of midbrain was decreased significantly in β-arrestin2 + /+ group and β-arrestin2 -/- group( t=3.512, 5.237, P=0.001, 0.000), while the number of Iba-1 + cells in SNc area of midbrain was increased significantly( t=5.816、8.402, P=0.000). Compared with β-arrestin1 + /+ group, the expressions of TRAF6, NF-κB and COX-2 in mouse microglia were significantly increased in β-arrestin1 -/- group( t=5.324, 5.837, 9.350, all P=0.0000). Compared with β-arrestin2 + /+ group, the expressions of TRAF6, NF-κB and COX-2 in mouse microglia were significantly down-regulated in β-arrestin2 -/- group( t=5.094, 6.318, 9.466, all P=0.000). Conclusions:The expression of β-arrestin1 is up-regulated and β-arrestin2 is down-regulated in brain tissue of PD mice.β-arrestin1/2 may affect the proliferation and activation of microglia and the loss of dopaminergic neurons through TRAF6/NF-κB/COX-2 pathway, and participate in the pathological process of PD.

Objective:To investigate the effects and significance of α-synuclein(α-syn)on the expression level of β-arrestin 2 in Parkinson's disease(PD)in a mouse model.Methods:Twenty-eight C57BL/6J mice with similar motor skills were randomly divided into a model group and a control group, with 14 mice in each group.A PD model was established by injecting preformed fibrils of α-syn into the striatum of the brain, and behavioral changes were monitored after 4 weeks.The expression levels of α-syn, the dopamine receptor(DR), tyrosine hydroxylase(TH), inflammatory factors, β-arrestin 2 and the nuclear transcription factor-κB(NF-κB)signaling pathway-related proteins were determined by Western blotting.The interaction between α-syn and β-arrestin 2 was detected by fluorescence resonance energy transfer(FRET), and the regulation of α-syn on β-arrestin 2 transcriptional activation was detected by the dual luciferase report assay.Results:After 4 weeks of modeling, compared with the control group, the average movement speed of mice in the model group was significantly reduced( t=9.415, P<0.001), the movement track was sparse and concentrated around the open field, and the time needed to climb the pole was significantly prolonged( t=16.412, P<0.001). Compared with the control group, the relative expression of α-synin in astrocytes in the model group increased significantly, the relative expressions of D1DR and TH decreased significantly[(1.14±0.18) vs.(0.53±0.16), (0.67±0.13) vs.(1.15±0.11), (0.46±0.05) vs.(0.81±0.06)]( t=9.810, 10.917 and 17.356, all P<0.001), the relative expression of tumor necrosis factor-α, interleukin-1β, interleukin-6 and NF-κB signaling pathway-related proteins increased significantly( t=3.583, 4.284, 5.396, 11.747, 16.375 and 18.294, all P<0.001), and the relative expression of β-arrestin 2 protein[(0.42±0.11) vs.(1.33±0.14)]in astrocytes decreased significantly( t=19.795, P<0.001). The FRET results suggested a possible direct interaction between α-syn and β-arrestin 2.The results of the dual luciferase report assay showed that the transcription activity of β-arrestin 2 was significantly increased after α-syn gene knockout. Conclusions:The α-syn may induce inflammation in astrocytes by activating the NF-κB signaling pathway and participate in the pathogenesis of PD by reducing dopamine biosynthesis and inhibiting its physiological function through negative regulation of β-arrestin 2.

Objective:The results of the two interferon-gamma release assay tests were compared, so as to provide reference for the laboratory to choose the detection method.Methods:Double blood samples of 96 suspected TB patients hospitalized in Civil Aviation General Hospital from July 2018 to December 2019 were collected, providing for TB specific antigen stimulation test by QIAGEN kit and Autobio kit respectively. ELISA and chemiluminescence were used to detect interferon-gamma, and the results were determined according to the manufacturer′s instructions. Based on the clinical or bacteriological evidence for diagnosis of tuberculosis, the consistency of the two kits was compared, and the diagnostic efficacy of tuberculosis was evaluated. At the same time, 60 samples of plasma stimulated by TB specific antigen in QIAGEN kit were randomly selected to detect interferon-gamma by ELISA and chemiluminescence respectively, and the consistency between the two interferon-gamma detection systems was compared. The Kappa coefficient were used to measure the consistency of the results. The ordinary linear regression and Bland-Altman plots were performed to show the differences of IFN-γ data between assays.Result:In 96 samples, the sensitivity and specificity of QIAGEN test were 81.82% (18/22) and 74.32% (55/74), and that of Autobio test were 72.73% (16/22) and 70.27% (52/74), respectively. The results of the two systems were consistent, Kappa value was 0.847, P<0.05. The area under ROC curve of QIAGEN test for diagnosis of tuberculosis was 0.807 (95% confidence interval: 0.702-0.911), while that of Autobio test was 0.765 (95% confidence interval: 0.640-0.889). Comparing the results of two systems for detecting interferon-gamma in the same plasma, the results of two systems were in good agreement ( R2=0.97, P<0.05); but there were significant differences in the levels of interferon-gamma in the same patient sample after stimulation with different negative and positive tubes ( R2=0.41, P<0.05). Conclusion:The results of γ-interferon release assay test of Autobio system and QIAGEN system are in good agreement, and the results of γ-interferon release assay test of the two systems are also in good agreement. Different amount of antigen coating, titer and test system may be responsible for the different release of interferon-gamma.

Objective:To investigate the expression of circ_0063865 in esophageal squamous cell carcinoma(ESCC)tissues and cells and its effect on the biological properties of the cells.Methods:The loop structure and stability of circ_0063865 were identified by Sanger sequencing, back-to-back primer validation and the ribonuclease R(Rnase R)tolerance assay.The expression of circ_0063865 was detected by RNA fluorescence in situ hybridization in an ESCC tissue microarray and its clinical relevance was analyzed.The expression levels of circ_0063865 in a normal esophageal epithelial cell line and ESCC cell lines were measured by real-time quantitative polymerase chain reaction(RT-qPCR). Cell counting Kit-8, the colony formation assay, the scratch assay, the transwell invasion assay and flow cytometry were used to detect the effects of circ_0063865 on cell proliferation, migration, invasion abilities and apoptosis, respectively.Results:The loop formation of circ_0063865 was verified by Sanger sequencing, back-to-back primer and Rnase R tolerance assays.The results of RNA fluorescence in situ hybridization showed that the mean fluorescence intensity of circ_0063865 expressed in ESCC tissues was significantly higher than in its paired paracancerous normal tissues( t=2.267, P<0.05). The expression of circ_0063865 was significantly associated with lymph node metastasis( χ2=4.356, P<0.05). The average overall survival time of patients with high circ_0063865 expression ESCC was lower than that of patients with low circ_0063865 expression ESCC.RT-qPCR results demonstrated that, compared with HEEC, circ_0063865 expression was elevated in ESCC cell lines( F=18.413, P<0.05). In addition, after circ_0063865 knockdown, the proliferation, migration and invasion abilities of KYSE-30 and KYSE-150 cells were significantly decreased, and the level of apoptosis was significantly increased(both P<0.05). Conclusions:The expression of circ_0063865 in ESCC is high, and changes in its expression are significantly correlated with lymph node metastasis.Additionally, circ_0063865 can promote the proliferation, migration and invasion of ESCC cells.

Objective To investigate the diagnostic value Tamm-Horsfall protein(THP)and osteopontin(OPN)in serum and 24-hour urine for urolithiasis.Methods A total of 101 patients with urolithiasis who underwent flexible ureteroscopy lithotripsy at the Urology Department of Civil Aviation General Hospital from April 2020 to March 2023 were included as the stone group,and 50 healthy individuals were enrolled as the control group.The samples of serum and 24-hour urine samples were collected from both the groups,and the levels of THP and OPN were measured using enzyme-linked immunosorbent assay(ELISA).Logistic regression analysis was performed to evaluate the association between each biomarker and urolithiasis,and receiver operating characteristic(ROC)curves were plotted to assess their diagnostic value.Results The stone group showed significantly lower THP levels(20.13[13.12,26.03]mg/d)and OPN levels(51.24[36.72,101.37]μg/d)in 24-hour urine,and THP levels(182.01[160.91,209.20]ng/mL)and OPN lev-els(18.76[15.72,22.48]ng/mL)in serum compared to the control group(all the P＜0.001).Binary Logistic regression analysis re-vealed that THP(OR=0.736,95％CI:0.606-0.895),OPN(OR=0.975,95％CI:0.958-0.993)and citrate(OR=0.067,95％CI:0.012-0.376)in 24-hour urine,and THP(OR=0.946,95％CI:0.908-0.986)and OPN(OR=0.896,95％CI:0.803-0.999)in ser-um were the protective factors for urolithiasis,while calcium level(OR=2.125,95％CI:1.243-3.633)24-hour urine was a risk factor(all the P＜0.05).ROC curve analysis showed that the areas under the curve(AUCROC)for the individual diagnosis of urolithiasis were 0.846,0.809,0.786,0.823,0.748,and 0.755 for the above six biomarkers,respectively.The AUCROC for the combined diagnosis u-sing THP+OPN in serum,THP+OPN in 24-hour urine and all the six biomarkers were 0.882,0.920 and 0.984,respectively,indica-ting better diagnostic performance.Conclusion The combined detection of the THP and OPN levels in serum and 24-hour urine may have good diagnostic value for urolithiasis and serve as potential diagnostic biomarkers.