1.Quantitative analysis of brain metabolites in systemic lupus erythematosus patients using multivoxel MR spectroscopy
Zhiyan ZHANG ; Yukai WANG ; Zhiwei SHEN ; Zhongxian YANG ; Li LI ; Xiaofang CHENG ; Dongxiao CHEN ; Renhua WU
Chinese Journal of Rheumatology 2016;(1):17-22
Objective To investigate the metabolite changes in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric symptoms using magnetic resonance spectroscopy (MRS) and explore the associations between image findings and clinical variables. Methods Twenty-two SLE patients with neuropsychiatric symptoms (NPSLE), twenty-one SLE patients without neuropsychiatric symptoms (non-NPSLE) and twenty healthy controls (HCs) underwent routine MRI scan and multivoxel magnetic reson-ance spectroscopy (MVS). The absolute metabolite concentrations were measured bilaterally in the posterior cingulate gyrus (PCG), dorsal thalamus (DT), lentiform nucleus (LN) and posterior paratrigonal white matter (PWM) using LCModel and SAGE software. The relationships between metabolite con-centrations and cognitive function scores were analyzed by Spearman rank correlation. Single-factor Chi-square analysis and t-test were used for analysis. Results ① Compared to control subjects, NPSLE patients had significantly lower N-acetylaspartate (NAA) values in bilateral PCG and DT, with the mean differences of -1.504 [95% confidence interval ( CI) (-2.335, -0.672), P=0.001], -1.460 [95%CI (-2.349, -0.570), P=0.002], -1.259 [95%CI (-1.894, -0.625), P=0.000] and -1.022[95%CI (-1.688, -0.356), P=0.003] for RPCG, LPCG, RDT and LDT, respectively. The concentration of total creatinine were observed to decline in RPCG and RDT, with the mean differences of-1.094 [95%CI (-1.845, -0.342), P=0.003], -0.955 [95%CI (-1.630, -0.280), P=0.006], -1.259 [95%CI (-1.894,-0.625), P=0.006] respectively. Glutamine and glutamate-values decreased significantly in RDT [mean difference=-2.586, 95%CI (-4.139, -1.033), P=0.002]. ② Compared to non-NPSLE patients, NPSLE patients had a lower NAA level in LPCG [mean difference=-1.256, 95%CI (-2.146, -0.367), P=0.006]. Positive correlations between mini-mental state examination scores [RPCG: rs=0.312, P<0.05; LPCG: rs=0.355, P<0.01], Montreal cognitive assessment scores (RPCG: rs=0.362, P<0.01; LPCG: rs=0.285, P<0.05) and NAA values in bilateral PCG were detected. Conclusion Both NPSLE and non-NPSLE patients may have metabolite dysfun-ctions in different brain regions. The cognitive disorder in SLE patients may be interpreted by neuronic damage of PCG.
2.Intervention effect of transcutaneous auricular vagus nerve stimulation on myocardial structural remodeling, electrical remodeling and apoptosis in rat heart failure model with preserved ejection fraction
Ming PENG ; Yukai LI ; Lan WANG ; Liang HUANG ; Zhong CHENG ; Jie XIAO
Chinese Journal of Geriatrics 2023;42(3):334-340
Objective:To observe the effect of percutaneous auricular vagus nerve stimulation on myocardial structural remodeling, electrical remodeling and apoptosis in rats of heart failure with preserved ejection fraction, and to explore the relationship between this effect and oxidative stress.Methods:The arteriovenous fistula was closed by ligation two weeks after establishment in SD rat.By increasing cardiac volume load in the short term, a rat model of heart failure with preserved ejection fraction was constructed.Forty rats were randomly divided into four groups, with 10 rats in each group: sham operation group(S), abdominal aorta-inferior vena cava fistula + closure group(AVF+ L), abdominal aorta-inferior vena cava fistula + closure+ percutaneous auricular vagus nerve stimulation group(AVF+ L+ tVNS)and abdominal aorta-inferior vena cava fistula + closure+ percutaneous auricular vagus nerve stimulation + acetylcholine M 2 receptor antagonist group(AVF+ L+ tVNS+ M -). Rats in the AVF+ L+ tVNS group received percutaneous vagal nerve stimulation on the basis of those in the AVF+ L group.Rats in the AVF+ L+ tVNS+ M - group received daily injection of acetylcholine M 2 receptor antagonist mesotramine(0.5mg/Kg)into tail vein on the basis of those in the AVF+ L+ tVNS group.The parameters of cardiac structural remodeling and electrical remodeling in each group were obtained by cardiac ultrasound and cardiac electrophysiological stimulator.Enzyme-linked immunosorbent assay(ELISA)was used to detect the values of B-type natriuretic peptide precursor(NT-proBNP)and oxidative stress-related indicators in each group.hematoxylin-eosin(HE)staining was used to observe the damage of myocardial structure, disorder of cell arrangement and infiltration of inflammatory cells.Cardiomyocyte apoptosis was observed by TdT-mediated dUTP nick end labeling(TUNEL)staining and apoptosis index was calculated.reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting were used to detect the mRNA and protein expression of B cell lymphoma / leukemia-2(BCL-2)and apoptosis promoting gene(BAX)in BCL-2 gene family. Results:The rats in the AVF + L group developed heart failure characterized by ventricular wall hypertrophy and diastolic dysfunction, and the left ventricular ejection fraction(LVEF)was >50 %.The rat heart failure model with preserved ejection fraction was successfully established.HE staining showed that the myocardial tissue structure damage, cell arrangement disorder and inflammatory cell infiltration were obvious in AVF+ L group, while the pathological changes of myocardial tissue in AVF+ L+ tVNs were significantly less than those in AVF+ L group.Compared with AVF+ L group, in the AVF+ L+ tVNs, the value of NT-proBNP decreased[(301.25 ± 16.07)ng/L vs.(79.33±5.63)ng/L, P<0.05], the value of E/A increased(1.28 ± 0.06 vs.1.66 ±0.05, P<0.05), the expression of BCL-2 mRNA[0.08(0.07, 0.08) vs.0.70(0.64, 0.76), P<0.05]and BCL-2 protein(0.19±0.03 vs.0.46±0.04, P<0.05)both increased, the expression of BAX mRNA(5.00±0.32 vs.2.14±0.36, P<0.05)and BAX protein(0.76±0.04 vs.0.43±0.05, P<0.05)both decreased, while the apoptotic index was also decreased(16.26±0.32 vs.7.04±0.24, P<0.05). Compared with AVF + L group, the indexes of myocardial structural remodeling, electrical remodeling and oxidative stress were decreased in AVF + L + tVNs group(P<0.05). Compared with AVF + L group, there was no significant difference in the above indexes in AVF + L + tVNS + M - group( P>0.05). Conclusions:tVNS can alleviate myocardial structural remodeling, electrical remodeling and apoptosis in HFpEF rats, which may be related to the reduction of oxidative stress response activity.
3.Disease burden of gestational complications associated with ozone pollution in the Yangtze River Delta region
Yukai CHENG ; Junyi NI ; Haixia DAI ; Wenjuan MA
Journal of Environmental and Occupational Medicine 2023;40(8):861-870
Background In recent years, ozone (O3) has gradually become a key air pollutant affecting public health. Studies have been conducted to evaluate O3 pollution-associated disease burden for general population, but there is a lack of research on O3 pollution-associated disease burden of gestational complications. Objective To assess the disease burden of O3 pollution on pregnancy complications in the Yangtze River Delta region and the changes in the disease burden resulting from the improvement of O3 pollution levels. Methods Through Chinese databases such as China National Knowledge Infrastructure (CNKI) and Wanfang, as well as English databases including PubMed and Web of Science, a systematic search was conducted to retrieve epidemiological studies investigating the association between O3 exposure and pregnancy complications from January 1, 2010 to February 28, 2023. Using predetermined inclusion and exclusion criteria, retrieved studies were screened and assessed for heterogeneity using the Higgins I2 statistic. The exposure increment was standardized to 10 µg·m−3, and a meta-analysis was conducted to evaluate the exposure-response relationship. Spatial analysis and environmental health risk assessment were then employed, using O3 monitoring data at national air monitoring stations, population data, and related disease burden parameters in the Yangtze River Delta region, to evaluate changes in the disease burden of pregnancy complications associated with improvements in O3 pollution levels. Results The meta-analysis revealed a significant association between maternal O3 exposure and increased risks of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP), particularly in early pregnancy, and the related odds ratios (OR) and 95% confidence intervals (CI) were 1.028 (1.002, 1.055) and 1.031 (1.023, 1.040), respectively. The cities with higher attribution fractions (AF) of GDM and HDP related to O3 exposure in 2017 and 2020 in the Yangtze River Delta region were Xuzhou, Huaibei, Suzhou (Anhui Province), Changzhou, and Wuxi, with most cities showing a significant decrease in AF in 2020. Except for Hefei, the cases of GDM and HDP attributable to O3 exposure in the remaining cities of the Yangtze River Delta region decreased by 16.31% to 57.41% in 2020 compared to 2017. In addition, except for Hefei, Suqian, Anqing, and Wuxi, the direct medical costs attributed to O3 exposure in the remaining cities decreased by 1.12% to 45.36% in 2020 compared to 2017. Conclusion Exposure to O3 during pregnancy is associated with increased risks of GDM and HDP. There are differences in the disease burden of GDM and HDP related to O3 pollution among cities in the Yangtze River Delta region in 2017 and 2020. In 2020, compared to 2017, the disease burden in most cities is decreased.