1.Long-term influence of splenectomy on immunity in advanced schistosomiasis patients
Yiming WU ; Chenxiao CAI ; Meiping TU ; Wenling WU ; Rengye DING ; Wenjun ZHU
Chinese Journal of Schistosomiasis Control 2009;21(6):550-552
A total of 55 cases of advanced schistosomiasis patients combined with Ⅲ-grade hepatic fibrosis and ascites were randomized into a splenectomy group and non-splenectomy group. The peripheral vein blood phlebotomized from these patients were detected for leucocytes, hematids, thrombocytes, acidophils, glutamic-pyruvic transaminase,alkaline phosphatase,albumin, total bilirubin,three-type precollagen, fore-type collagen, hyaluronic acid, IgG, IgA, C_3, C_4 and the sub-group of lymphocytes such as CD3、CD4、 CD8 、CD56 + 16. There were no significant difference on hepatic function and the level of hepatic fibrosis between the groups above metioned. It could be found that leucocytes, thrombocytes, IgG, IgA, CD56 + 16 increased while CD3, CD4, and albumin decreased in the splenectomy group. In conclusion, leucocytes and thrombocytes increase after splenectomy, cytoimmunity declines and humoral immunity enhances.
2.Whole-genome sequencing analysis of the victim exposed to a super high dose of iridium-192 during the Nanjing radiological accident in 2014
Daojiang YU ; Wenling TU ; Zhiqiang JIANG ; Min WANG ; Yuhong SHI ; Yulong LIU ; Youyou WANG ; Shuyu ZHANG
Chinese Journal of Radiological Medicine and Protection 2021;41(4):247-252
Objective:To investigate radiation-induced somatic mutations and variations and provide theoretical basis for clarifying radiation-induced genetic changes and long-term effects by whole-genome sequencing analysis of the genetic variations of the victim of the " 5.7" 192Ir radiation accident in Nanjing. Methods:Normal back skin tissue, irradiated bone and soft tissues, and peripheral blood were collected from the victim 2 047 days post-irradiation. DNA of these samples was extracted and sequenced with high-throughput genomics and analyzed by bioinformatics method. The genetic variations of between irradiated and normal tissues were compared.Results:Compared with normal back skin tissue, there are large amounts of genetic variations in the irradiated bone and soft tissues and peripheral blood, including base substitution (transition, transversion), small insertion, small deletion, copy number variation (gain, loss) and structure variation (large deletion, large duplication, inversion, intra-chromosomal translocation, inter-chromosomal translocation). There were 10 666 genetic variations in the irradiated bone and soft tissues and 11 233 genetic variations in peripheral blood, where thousands of genes were involved in. These variations occurred in the exons, introns, UTR′3, UTR′5, splicing sites, within 5 kb upstream of transcription initiation site, within 5 kb downstream of transcription termination site, ncRNA and intergenic region. All chromosomes had genetic variations.Conclusions:There were a large number of genetic variations in the irradiated tissues and blood of the victim at 2 047 days after irradiation, which may affect the body function and cause the long-term effects.
3.Effect of ionizing radiation on ferroptosis of skin cells and the radioprotective role of ferroptosis inhibitor Ferrostatin-1
Yahui FENG ; Sheng JIANG ; Wenling TU ; Jichun SHAO ; Daojiang YU ; Jingyi LI ; Shuyu ZHANG
Chinese Journal of Radiological Medicine and Protection 2021;41(8):602-608
Objective:To investigate the effect of ionizing radiation on the ferroptosis of skin cells and the potential therapeutic strategy of ferroptosis inhibitor Ferrostatin-1 (Fer-1) on irradiated skin cells.Methods:HaCaT cells were pre-treated with Fer-1 before X-ray irradiation. After irradiation, CCK-8 assay and LDH release assay were used to detect cell viability and cell death, flow cytometry was used to detect the lipid peroxidation levels, crystal violet staining assay was used to detect colony forming ability, and the expressions of ferroptosis related proteins ACSL4 and GPX4 were detected by Western blot.Results:The cell viability of HaCaT cells was significantly decreased ( t=5.63, 8.74, P<0.05) and the release of LDH was significantly increased ( t=3.98, 5.08, 9.27, P<0.05) after different doses of X-ray irradiation. The cell viability was improved ( t=5.79, P<0.05) and the release of LDH was reduced ( t=12.36, 11.96, 18.13, 9.96, P<0.05) after the pre-treatment with Fer-1. The lipid peroxidation levels of HaCaT cells were significantly increased ( t=9.59, P<0.05) and the clonogenic survival ability were reduced ( t=4.26, P<0.05) after 10 Gy X-ray irradiation, while Fer-1 pre-treatment reduced ( t=6.48, 17.04, P<0.05) the increase of lipid peroxidation level induced by X-ray irradiation and also effectively restore ( t=3.96, P<0.05) the clonogenic survival ability. The expressions of ACSL4 and GPX4 were decreased after 10 Gy X-ray irradiation, while they recovered to normal level ( t=5.23, 7.16, 4.78, 8.29, 6.43, P<0.05) after the pre-treatment with Fer-1. Conclusions:Ferroptosis inhibitor Fer-1 alleviates the progress of radiation-induced skin injury by inhibiting ferroptosis after ionizing radiation at the cellular level, which provides a potential strategy for the protection of radiation injury.
4.Proteomic analysis of radiation-induced esophagitis in rats
Yuehua ZHANG ; Hangfeng LIU ; Shuyu ZHANG ; Mengjie DU ; Xiaochen MENG ; Wenling TU
Chinese Journal of Radiological Medicine and Protection 2024;44(9):725-733
Objective:To investigate the impacts of ionizing radiation on protein expression profiles in esophageal tissues of rats using quantitative proteomics, in order to reveal the molecular mechanisms underlying the onset and development of radiation-induced esophagitis (RIE).Methods:A total of twenty-four male SD rats were divided by simple randomization into three groups: the control, 25 Gy irradiation, and 35 Gy irradiation groups, and their esophageal tissues were collected at 7 d post-irradiation to extract total protein. Then, changes in the protein expression profiles of the esophageal tissues in irradiated rats were investigated using tandem mass tag (TMT)-labeled quantitative proteomics and bioinformatics analysis. Additionally, the expressions of two key proteins, Hp and Ndufs4, were validated using immunohistochemistry and Western blot.Results:A comparison with the control group revealed a total of 847 differentially expressed proteins (DEPs; 483 up-regulated and 364 down-regulated) following 25 Gy irradiation and 699 DEPs (443 up-regulated and 256 down-regulated) following 35 Gy irradiation. Different radiation doses led to common 326 up-regulated proteins, which were mainly involved in biological processes and signaling pathways related to immune and inflammatory responses, and 210 down-regulated proteins, which were primarily involved in biological processes and signaling pathways related to energy production and metabolism. Furthermore, a total of 155 proteins were screened using a constructed protein protein interaction(PPI) network. Of these proteins, the up-regulated ones were most associated with three functional pathways, namely innate immune responses, complement and coagulation cascades, and innate immune system, while the down-regulated ones were most associated with energy acquisition via oxidizing organic compounds, oxidative phosphorylation, and the tricarboxylic acid (TCA) cycle and respiratory electron transfer. These functions were enriched with nine complement-related up-regulated and five mitochondria-related down-regulated proteins, respectively. Ionizing radiation significantly up-regulated Hp ( t = 27.94, 10.96, P<0.001) and down-regulated Ndufs4 ( t = 59.27, 54.07, P<0.001), consistent with the protein sequencing result. Conclusions:Ionizing radiation can change the protein expression profiles in the esophageal tissues of rats, and these DEPs are involved in multiple radiobiology-related functional pathways such as immune processes, inflammatory responses, and abnormal energy metabolism. Screening and validation of key proteins are helpful for identifying potential biomarkers of radiation-induced esophagitis.
5.Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of Radial Glial Cells, Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice.
Xue LI ; Shimin ZOU ; Xiaomeng TU ; Shishuai HAO ; Tian JIANG ; Jie-Guang CHEN
Neuroscience Bulletin 2023;39(7):1131-1145
Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders (NDDs) that exhibit delayed speech development, intellectual disability, and congenital abnormalities. The etiology of NDDs is unclear. Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells (RGCs), respectively, in the mouse neocortex during early gestation. Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone (VZ). Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ. The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs. The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions, the loss of which leads to periventricular heterotopias. We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.
Mice
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Animals
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Ependymoglial Cells/physiology*
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Cadherins
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Neurons/metabolism*
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Cerebral Cortex/metabolism*
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Cell Differentiation
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Cell Movement
6.Exploring Central Regulatory Effect of Chaishao Liujuntang on Chronic Atrophic Gastritis Rats with Liver Depression and Spleen Deficiency Syndrome Based on Metabolomics
Yinjie HONG ; Wenling TU ; Jingru ZHU ; Wenqian LUO ; Kaiyue HUANG ; Huijuan GAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):148-155
ObjectiveBased on ultra performance liquid chromatography-mass spectrometry(UPLC-MS) and non-targeted metabolomics technology to discuss the central regulatory effect of Chaishao Liujuntang on chronic atrophic gastritis(CAG) rats with liver-depression and spleen-deficiency, and to look for the correlation between cerebral cortex, hypothalamus and metabolic status of gastric tissues. MethodA CAG rat model with liver-depression and spleen-deficiency was established by chemical induction, hunger and satiety disorders, chronic restraint and tail clamping stimulation, lasting for 16 weeks. Twenty-eight Wistar rats were randomly divided into a blank group of 8 rats and a model group of 20 rats. After the completion of modeling, 4 rats in the model group were taken to observe the pathological changes of gastric mucosa. The remaining model rats were randomly divided into a model group of 8 rats and a Chaishao Liujuntang group of 8 rats. Chaishao Liujuntang group rats were given 5.1 g·kg-1 by gavage, and the remaining rats were given equal volume sterilized water by gavage for 4 weeks. Macroscopic characteristics, behavioral indicators and histopathological changes of the gastric mucosa of rats in each group were observed and compared. UPLC-MS non-targeted metabolomics was used to explore the metabolic regulation effect of Chaishao Liujuntang on the cerebral cortex, hypothalamus and stomach tissues of CAG rats with liver-depression and spleen-deficiency. Pearson correlation coefficient method was used to analyze the correlation between different tissue metabolites. ResultCompared with the model group, the macroscopic characteristics of rats in Chaishao Liujuntang group were improved, such as hair color, mental state and stool properties, and the number of times of crossing and standing in the open field experiment was significantly increased, and the static time of forced swimming was significantly reduced(P<0.01), and the gastric mucosa atrophy was reduced. The metabolic data from the cerebral cortex of rats in each group identified a total of 3 common potential biomarkers, but not enriched in pathways, 26 common potential biomarkers were identified in the hypothalamus, and the key metabolic pathways involved were mainly enriched in purine metabolism, glycerol phospholipid metabolism, D-glutamine and D-glutamic acid metabolism. Seventeen common potential biomarkers were identified in the stomach, and the key metabolic pathways involved were mainly enriched in thiamine metabolism, valine, leucine and isoleucine biosynthesis, and taurine and taurine metabolism. Correlation analysis of metabolites in different tissues revealed that multiple amino acids and their derivatives mediated metabolic connections between the cerebral cortex, hypothalamus and stomach of rats. ConclusionThe metabolic disorders in the cerebral cortex, hypothalamus and stomach of CAG rats with liver-depression and spleen-deficiency have their own characteristics, mainly manifested by changes in the content of glycerol phospholipids, fatty acids and bile acid metabolites. Moreover, Chaishao Liujuntang may play a central regulatory role in CAG rats with liver-depression and spleen-deficiency by correcting the metabolic disorders of amino acids.
7.Epidemiological study on antibiotic resistance among Helicobacter pylori in Taizhou district, Zhejiang, 2010-2013.
Tiangan YANG ; Hongzhang LI ; Jiaoe CHEN ; Wanli ZENG ; Junliang MAO ; Zhihua ZHANG ; Junhua YANG ; Ningmin YANG ; Miaoying TU ; Jianzhong ZHANG ;
Chinese Journal of Epidemiology 2014;35(6):704-707
OBJECTIVETo study the infection status of Helicobacter pylori (H. pylori) and sensitivity to commonly used antibiotics in Taizhou district,Zhejiang province.
METHODS39 099 cases aged between 5 and 95 years old (mean as 48.42 years) were involved during January 2010 to December, 2013 for this study. Sex ratio was 1 : 0.95. Yearly distribution of the number of cases were 5 031, 6 709, 11 902 and 15 457 in 2010, 2011, 2012 and 2013, respectively. Gastric mucosal specimens were collected and H. pylori strains were isolated and cultured in the same platform in Zhiyuan Medical Inspection Institute of Hangzhou. Resistance tests of all the H. pylori isolates were performed to 6 commonly used antibiotics:metronidazole, clarithromycin, amoxicillin, gentamicin, levofloxacin and furazolidone with the agar dilution method. The antibiotic resistance rates of H. pylori strains isolated during year 2010-2013 and the changing trends were analyzed.
RESULTSResistance rates to levofloxacin and clarithromycin kept at higher level and the highest was in 2011 and then decreased in both 2012 and 2013 (P < 0.01). The resistance rates to both levofloxacin and clarithromycin reached the highest in 2011 (P < 0.01), and decreased thereafter, with no significant change in 2013 to 2012 (P > 0.05).
CONCLUSIONAntibiotic resistance rate against metronidazole for HP isolate was highest. Resistance rate against amoxicillin and furazolidone, gentamicin was low. Clinical treatment should choose amoxicillin and furazolidone, gentamicin. The resistance rates to levofloxacin and clarithromycin had been seen at a significantly downward trend since 2011. However, the combined resistance rates to levofloxacin and clarithromycin did not seem to reduce since 2012.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents ; pharmacology ; Child ; Child, Preschool ; Drug Resistance, Multiple, Bacterial ; Helicobacter pylori ; drug effects ; isolation & purification ; Humans ; Middle Aged ; Young Adult