1.Intestinal tissue injury and gut microbiome changes in mice treated with whole body irradiation by gamma rays
Min DUAN ; Zhe YANG ; Ying LIU ; Yongyi WANG ; Yumeng YE ; Yanhui HAO ; Hongyan ZUO ; Yang LI
Military Medical Sciences 2024;48(9):641-649
Objective To investigate the effects of 0.5 Gy 60Co γ-ray irradiation on intestinal tissue injury and intestinal microflora in mice.Methods C57BL/6N mice were irradiated with 0.5 Gy 60Co γ-ray at 1 d,3 d,7 d and 14 d after irradiation.Jejunum tissues were fixed and frozen,and feces were frozen.Hematoxylin-eosin staining was used to observe the pathological injury to jejunum after irradiation,ki67 immunohistochemical staining was adopted to detect the proliferation of jejunum crypt cells,and TdT-mediated dUTP nick end labeling was employed to detect the apoptosis of jejunum crypt cells.The expressions of TNF-α,IL-1β,IL-6 and IL-10 cytokines in small intestines were detected via radioimmunoassay.The changes of intestinal flora in mice after irradiation were analyzed by metagenomic sequencing,and LEfSe analysis and ROC analysis were used to screen the bacteria with significant differences.Results After 0.5 Gy 60Co γ-ray irradiation,the proliferative cells of the jejunal crypt were significantly decreased at 1 d after irradiation(P<0.05),while the apoptotic cells were significantly increased at 1 and 3 d after irradiation(P<0.01).The expression of TNF-α at 7 and 14 d after irradiation,that of IL-1 β at 1,3,7 and 14 d after irradiation and that of IL-6 at 3,7 and 14 d after irradiation were significantly increased(P<0.05),while the expression of IL-10 at 7 and 14 d after irradiation was significantly decreased(P<0.05).After 0.5 Gy 60Co γ-ray irradiation,intestinal flora composition changed significantly at phylum,genus and species levels,and Lactobacillus murinus,Lactobacillus johnsonii,Alistipes-unclassified,Mucispirillum schaedleri underwent the most significant changes and had higher LDA scores.Conclusion The whole body irradiation of 0.5 Gy 60Co γ-ray can cause intestinal tissue damage and change the composition of intestinal flora in mice.
2.Effects of 2 650 MHz radiofrequency radiation on the behavior and hippocampal neurotransmitter release of mice
Yujie LIU ; Jun WANG ; Keqin LI ; Chenxu CHANG ; Ying LIU ; Hongyan ZUO ; Yang LI ; Hong YANG ; Yanhui HAO ; Hua DENG
Chinese Journal of Radiological Medicine and Protection 2024;44(5):354-360
Objective:To investigate the effects of 2 650 MHz radiofrequency (RF) exposure on the behavior and neurotransmitter release of mice.Methods:Adult male C57BL/6N mice were divided into a normal control (CON) group and a radiofrequency radiation (RFR) group using the random number table method. The mice in the RFR group were subjected to single-dose whole-body exposure to a uniform 2 650 MHz RF electromagnetic field for 3 h. During the RF exposure, the field strength in the effective working area of the RF radiation platform was measured using an electromagnetic radiation analyzer, and the changes in the anal temperature of the mice were monitored using an optical fiber thermometer. Moreover, the changes in the cognition, social interaction, and emotion of the mice were determined through the new object recognition test, social preference test, and open field test. Finally, the changes in the hippocampal neurotransmitter release levels of the mice were detected using microdialysis sampling and mass spectrometry, and the changes in the hippocampal tissue structure and ultrastructure were observed via microscopy.Results:Under the test conditions, RF radiation improved the anal temperature of the mice, with a maximum increasing amplitude of 0.61℃, falling within the range of thermal safety. The mice in the RFR group experienced a significant decrease in the frequency and time for exploring new objects ( t=4.50, 2.53, P < 0.05) in the new object recognition test, a significant decrease in the frequency ( t=0.08, P<0.01) and time ( t=0.03, P<0.05) for exploring other mice in the social preference test, and no significant change in the frequency and time for exploring the central area ( P > 0.05) in the open field test. Compared to the CON group, the RFR group showed an increase in the release of 5-hydroxytryptamine (5-HT) ( t=-2.56, P < 0.05) and a decrease in the release of acetylcholine (ACh) ( t=2.21, P < 0.05), no significant difference in the release of glutamate (Glu) and γ-aminobutyric acid (GABA) ( P > 0.05), and no evident damage to the hippocampal tissue and structure and synaptic ultrastructure. Conclusions:2 650 MHz RF radiation may induce cognitive impairment and abnormal social preference in mice, which is attributed to neuronal dysfunctions and neurotransmitter release disorders under RF exposure.
3.Histopathological changes in secondary visual cortex and enhanced calcium activity in neurons being involved in microwave radiation-induced anxiety-like behavior
Zhihua FENG ; Ting PAN ; Ganghua HE ; Chenxu CHANG ; Zhilin CUI ; Meiying YANG ; Yanhui HAO ; Fengsong LIU ; Yang LI ; Hongyan ZUO
Chinese Journal of Radiological Medicine and Protection 2024;44(6):464-471
Objective:To clarify the effects of microwave radiation on anxiety-like behavior, the histomorphology of the secondary visual cortex, and calcium activity in neurons.Methods:36 C57BL/6N mice were selected and divided into control group and microwave radiation group according to the random number table method. In the simple behavioral testing, there were 8 mice in the control group and 7 mice in the radiation group. Combining fiber optic recording with behavioral experiments, there were 8 mice in the control group and 7 mice in the radiation group. Hematoxylin-eosin (HE) staining was conducted with 3 mice in each group. A high-power microwave simulated source in the X-band with a center frequency of 9.875 GHz and an average power density of 12 mW/cm 2 was used to irradiate the mice for 15 minutes, establishing a microwave radiation animal model. Then, anxiety-like behavior changes in the radiation group were identified using the open-field and elevated plus maze (EPM) tests. The effects of microwave radiation on the histomorphology of the secondary visual cortex were investigated using HE staining and optical microscopy. Based on the genetically encoded calcium imaging technique, as well as optical fiber recording combined with behavioral paradigms in the open field and the EPM, the changes of calcium activity in neurons in the V2M region of the secondary visual cortex were detected. Results:Compared to the control group, the radiation group showed a significant decrease in the frequency of exploring the central region of the open field and the open arm of the EPM ( t = 2.24, 3.10, P < 0.05). Furthermore, the radiation group exhibited the degeneration and apoptosis of some neurons in the secondary visual cortex, primarily manifested as pyknosis and deep staining, cell body shrinkage, and the slightly widening of perivascular space. Fiber optic recordings and behavioral experiments indicated that compared to the control group, mice in the radiation group exhibited significantly increased calcium activities in neurons of the secondary visual cortex when exploring the central region of the open field ( t = -2.75, P < 0.05) or the open arm of the EPM ( t = -2.77, -3.41, P < 0.05) compared to those before radiation after microwave exposure. Conclusions:Microwave radiation can induce anxiety-like behaviors and histopathological changes in the secondary visual cortex. Increased calcium activity in neurons of the secondary visual cortex is proved to be an important mechanism underlying the changes in anxiety-like behavior due to microwave radiation.
4.Mechanism of the therapeutic effect of Tetrandrine on striatum injury caused by microwave radiation
Xiaoxu KONG ; Zhihua FENG ; Xuejia WANG ; Ganghua HE ; Ting PAN ; Zhengtao XU ; Yumeng YE ; Yanhui HAO ; Hongyan ZUO ; Yang LI
Chinese Journal of Radiological Medicine and Protection 2023;43(5):328-334
Objective:To study the therapeutic effect Tetrandrine (TET) on striatal injury caused by microwave radiation and underlying mechanism.Methods:C57BL/6N mice were randomly divided into blank control group (C), radiation control group (R), TET group (TET) and TET combined with radiation group (TET+ R). The mice of radiation group were exposed to 2.856 GHz 8 mW/cm2 microwave on whole-body for 15 min. TET (60 mg/kg) was injected intraperitoneally once a day for 3 consecutive days. The TET structure was verified by ultraviolet spectrophotometry. The open field experiment was used to detect the change of anxiety in mice. Histopathological and ultrastructural changes of the striatum were observed by light microscopy and transmission electron microscopy (TMT). Quantitative real-time PCR (qPCR) was used to detect gene expression changes of voltage-gated calcium channel (VGCC) subtype in the striatum.Results:The open field experiments showed that the time and distance of mice to explore the central region after microwave radiation were significantly lower than that before radiation ( t=4.60, 5.18, P<0.01), and the TET administration significantly improved these changes ( F=1.43, 4.37, P < 0.05). 7 d after microwave radiation, some neuronal nuclei in the striatum of mice contracted and could be stained deeply, which was more obvious in the globus pallidus area. The partial neuronal apoptosis, swelling and cavitation of glial cell mitochondria, blurring of synaptic gaps, and widening of perivascular gaps in the striatum were observed by TMT. The above lesions were significantly rescued after TET administration. But both microwave radiation and TET administration had no significant effect on the gene expressions of striatal VGCC ( P > 0.05). Conclusions:TET has a therapeutic effect on anxiety-like behavior and structural damage of striatum caused by microwave radiation, which is independent of the expression of striatal VGCC genes.
5.Long-term prognostic value of coronary CT angiography-derived fractional flow reserve in elderly patients with CHD
Jingzhou JIANG ; Xiang GUO ; Rui ZUO ; Qian CHEN ; Hongyan QIAO ; Bangjun GUO ; Pengpeng XU ; Tongyuan LIU ; Longjiang ZHANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2023;25(12):1255-1259
Objective To evaluate the long-term prognostic value of coronary CT angiography-derived fractional flow reserve(CT-FFR)in elderly patients with coronary heart disease(CHD).Methods A retrospective analysis was performed on 1133 patients with clinically suspected CHD from a prospective observational study based on coronary CTA and CT-FFR at the General Hos-pital of Eastern Theater from April 2018 to March 2019,and 330 elderly CHD patients were even-tually included.According to major adverse cardiovascular events(MACE)occurred or not,295 patients were assigned into non-MACE group and 35 patients into the MACE group.Based on cor-onary CTA data,plaque features were analyzed and CT-FFR values were measured in all lesioned vessels.The relationship of plaque features and CT-FFR with MACE was evaluated by using Cox proportional risk regression model,Kaplan-Meier survival curve,and ROC curve analyses.Results The patients with coronary stenosis(≥50%)or CT-FFR value ≤0.8 had a higher risk of MACE(P<0.01).Univariate Cox analysis showed that coronary stenosis ≥50%and CT-FFR value 0.8 were risk factors of MACE(P<0.01).After adjusting confounding factors,multivariate Cox analysis indicated that CT-FFR ≤0.8(HR=17.037,95%CI:5.060-57.358,P=0.000)was only independent predictor for MACE.The risk prediction model based on CT-FFR presented better performance than the model based on coronary CTA stenosis(C-index:0.820 vs 0.696,P=0.000).Conclusion CT-FFR≤0.8 is an important independent predictor for long-term MACE in elderly CHD patients.Clinical risk stratification based on CT-FFR may optimize prognostic man-agement strategies in these patients.
6.Influence of microwave radiation on associative learning and memory function and hippocampal structure in mice
Cuicui HU ; Chenxu CHANG ; Xiaoxu KONG ; Yadong LIU ; Yumeng YE ; Yanhui HAO ; Hongyan ZUO ; Yang LI
Chinese Journal of Radiological Medicine and Protection 2022;42(7):481-486
Objective:To investigate the effects of microwave radiation on associative learning and memory function and hippocampal structure of mice.Methods:C57BL/6N mice were ramdomly divided into sham-radiated group ( n=27) and radiation group ( n=2). The radiation group was exposed to microwave at 2.856 GHz, 8 mW/cm 2 for 15 min, then their spatial and associative learning and memory function were examined with the morris water maze and shuttle box behavior experiment. The pathological changes of hippocampal tissue were observed by HE staining and light microscope, the ultrastructural changes of hippocampal tissue were observed by transmission electron microscope. Results:After microwave radiation, the times of mice crossing the platform for the reverse space exploration decreased from(3.60±0.79) times to (2.55±0.47) times( t=2.21, P=0.046), the average active escape rate decreased significantly ( t = 2.70, P<0.05), and the average active latency and the total shock time was significantly prolonged ( t = -3.09, -3.02, P < 0.05). At 8 d after microwave radiation, the nuclei of some neurons in the CA3 and DG regions of the hippocampus were pyknosis. The neurons were apoptotic, the synaptic spaces blurred, the glial cells swollen, and the perivascular spaces widened in the CA3 region of the hippocampus. Conclusions:Microwave radiation can decline the spatial reference memory ability and associative learning and memory ability of mice. The morphological and pathological changes of hippocampus are the structural basis of this dysfunction.
7.Clinical effect of high-titer plasma in the treatment of severe viral pneumonia in children
Hongyan PENG ; Feiyan CHEN ; Yunlong ZUO ; Run DANG ; Yiyu YANG
Chinese Journal of Emergency Medicine 2020;29(7):970-975
Objective:To explore the clinical effect of high-titer plasma in the treatment of severe viral pneumonia in children.Methods:A total of 80 eligible children with severe viral pneumonia in intensive care unit of Guangzhou Women and Children Medical Center were enrolled in this retrospective study from January 2016 to June 2019, According to whether high-titer plasma was used or not, patients were divided into the high-titer plasma group (40 cases) and non-high-titer plasma group (40 cases). Chi-square test, Fisher's exact probability test and Mann-Whitney U test were used to compare the basic data, infection indicators, blood gas and ventilator parameters related indicators, treatment and prognosis of the two groups. Results:There were no significant differences in age, sex, admission weight, onset days and fever days between the high-titer plasma group and non-high- titer plasma group before entering the study (all P>0.05); There were no significant differences in the worst SOFA score, Murray lung injury score, chest X-ray involvement and sepsis within 3 days (all P>0.05). There were no significant differences in white blood cells, neutrophils and c-reactive protein between the two groups before and after entering the study (day 3 and 7) (all P> 0.05). There were no significant differences in arterial partial pressure of oxygen (PaO 2), partial pressure of carbon dioxide (PaCO 2), lactic acid (Lac), mean airway pressure (MAP), oxygenation index (P/F) and oxygen index (OI) between the two groups before and after entering the study (day 1, 3 and 7) (all P>0.05). There were no significant differences in the use of immunoglobulin, hormone, fiberoptic bronchoscope, blood purification, high frequency ventilator, pulmonary surfactant and extracorporeal membrane between the two groups (all P>0.05). There were no statistical differences in the number of days using invasive ventilator, the number of days staying in PICU and the total length of hospital stay between the two groups (all P>0.05). There was shorter time of the body temperature decreased to normal time in the high-titer plasma group than in the non-high-titer plasma group ( Z=-2.10, P=0.04). The survival rate of the high-titer plasma group was higher than that of the non-high-titer plasma group (85% vs 65%, χ2=4.27, P=0.04). The average daily cost of the high-titer plasma group was less than that of the non-high-titer plasma group, 3 688.38 yuan (2 335.49, 5 741.51) yuan vs 3 979.24 yuan (2 670.68, 9 992.62) yuan, but the difference was not statistically significant (Z=-1.35, P=0.18). No serious adverse reactions were observed during the treatment with high-titer plasma. Conclusions:The treatment of severe viral pneumonia with high-titer plasma can shorten fever time and improve survival rate. High-titer plasma can be used as a safe and effective treatment for severe viral pneumonia.
8.Clinical observation of 70 children with severe pneumonia induced by adenovirus type 7
Feiyan CHEN ; Run DANG ; Hongyan PENG ; Wenmin YANG ; Chunmin ZHANG ; Yunlong ZUO ; Jie HONG ; Mingqi ZHAO ; Yi CHEN ; Yiyu YANG
Chinese Pediatric Emergency Medicine 2020;27(8):587-590
Objective:To explore more clinical characteristics and outcomes of children with severe pneumonia induced by adenovirus type 7(Adv-7).Methods:Seventy children with severe pneumonia induced by Adv-7 admitted to the pediatric intensive care unit of Guangzhou Women and Children′s Medical Center from January 2016 to October 2019 were enrolled.The clinical features, treatments and outcomes of these children were recorded.Results:(1)There were 43 males(61.4%)and 27 females(38.6%). Thirty(42.9%)patients were 0-12 months old, 28(40.0%)patients were 13-36 months old, and 12(17.1%)patients were over 36 months old.(2)The average onset time of severe pneumonia induced by Adv-7 was(11.87±7.10)days before being admitted to PICU.The average sequential organ failure assessment score was 6.80±3.13.The average Murray lung injury score was 2.49±1.15.The average P/F value was(150.57±86.25)mmHg(1 mmHg=0.133 kPa). Sixty-four cases(91.4%)were involved in two or more area of lung on X-rays.All cases were diagnosed with sepsis.(3)Laboratory examination: white blood cell count was(7.6±5.5) ×10 9/L, platelet count was(238.8±164.2)×10 9/L, and C-reactive protein was(39.4±37.2)mg/L.(4)Treatments: intravenous gamma globulin was used in 65 cases(92.9%). Intravenous glucocorticoid was used in 45 cases(64.3%). Fiberoptic bronchoscopy was performed in 43 cases(61.4%). Blood purification treatment was performed in 21 cases(30%). Sixty-three patients(90.0%)were treated with non-invasive or invasive ventilator, high frequency ventilator-assisted ventilation was used in 20 cases(28.6%). Surfactant was used in six cases(8.6%). Extracorporeal membrane oxygenation was used in 19 cases(27.1%). (5)The average treatment time for ventilation was(13.10±11.58)days.The average time for temperature recover was(4.69±4.01)days in PICU.The average PICU stay time was(15.76±12.20)days.The average length of stay was(27.04±13.10)days.There were 16 patients died and the mortality was 22.9%. Conclusion:The children with severe pneumonia induced by Adv-7 were critical and had significant lung injuries.Suffering from active clinical treatment such as extracorporeal membrane oxygenation, some of these patients still had poor prognosis.
10.Effect of DA-JC4 on postoperative neuroinflammatory responses in aged rats
Hongyan GONG ; Fang ZHENG ; Zhichao ZUO ; Jingjing LIU ; Qingzhi WANG ; Guoan ZHAO
Chinese Journal of Anesthesiology 2020;40(5):588-591
Objective:To evaluate the effect of glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist DA-JC4 on postoperative neuroinflammatory responses in aged rats.Methods:Forty-five Sprague-Dawley rats, aged 21-23 months, weighing 530-630 g, provided by the Animal Experiment Center of Medical School of Zhengzhou University, were assigned into 3 groups ( n=15 each) using a random number table method: sham operation group (group S), operation group (group O) and DA-JC4 group (group G). Rats underwent exploratory laparotomy under anesthesia with chloral hydrate in O and G groups.In group G, DA-JC4 10 nmol/kg (dissolved in 1 ml of sterile normal saline) was intraperitoneally injected immediately after the end of operation and at 24 and 48 h after operation.Western blot was used to determine the expression of hippocampal Bax, Bcl-2, activated caspase-3, Beclin-1, microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), high-mobility group box 1 protein (HMGB1), interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) on day 3 after surgery.The Morris water maze test was performed on days 14-18 after operation to assess the cognitive function. Results:Compared with group S, the escape latency was significantly prolonged on days 15-18 after operation in group O and on day 18 after operation in group G, and the number of crossing the original platform was reduced, the time spent in the target quadrant was shortened, the expression of activated caspase-3, Bax, LC3Ⅱ, HMGB1, IL-1β and TNF-α in hippocampi was up-regulated, and the expression of Bcl-2, LC3Ⅱ and Beclin-1 was down-regulated in O and G groups ( P<0.05). Compared with group O, the escape latency was significantly shortened, and the number of crossing the original platform was increased, the time spent in the target quadrant was prolonged, the expression of activated caspase-3, Bax, LC3Ⅱ, HMGB1, IL-1β and TNF-α in hippocampi was down-regulated, and the expression of Bcl-2, LC3Ⅱ and Beclin-1 was up-regulated in group G ( P<0.05). Conclusion:The mechanism by which DA-JC4 reduces postoperative cognitive dysfunction may be related to inhibiting neuroinflammatory responses in aged rats.

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