1.Mechanism of ionizing radiation affecting the fertility of offspring through sperm DNA methylation in mice
Zhihui DAI ; Jiawei WU ; Haozan YIN ; Yuefan WANG ; Jian TAN ; Fu YANG
Academic Journal of Naval Medical University 2025;46(10):1257-1266
Objective To explore the effect of ionizing radiation on the fertility of male mice and its offspring and the intergenerational and transgenerational genetic effect mechanism of ionizing radiation through sperm DNA methylation sequencing.Methods Eight-week-old(8 w)C57BL/6 male mice were irradiated with 60Co radiation source at a dose of 3 Gy(3 Gy-F0 group,n=60)and non-irradiated mice of the same age were used as controls(0 Gy-F0 group,n=60).Afetr 5-,6-,7-,8-,9-,10-,11-,and 12-week radiation,the mice began to breed with healthy females,and the first generation(F1 generation)male mice then breed with healthy female mice to obtain the offspring(F2 generation)male mice.The structure of testis was detected by hematoxylin-eosin staining;serum follicle-stimulating hormone(FSH),testosterone(T)and luteinizing hormone(LH)levels were determined by enzyme-linked immunosorbent assay.Automatic sperm analysis system was used to detect sperm concentration and activity.The DNA of F0 generation sperm was extracted and analyzed by genome-wide DNA methylation sequencing.MassARRAY methylation sites were detected in sperm DNA of F1 generation mice and verified by quantitative polymerase chain reaction(qPCR).Results Compared with the 0 Gy-F0 group,male mice in the 3 Gy-F0 group gradually regained their reproductive ability 7 weeks after ionizing radiation.There was no significant difference in the number of surviving offspring between the 3 Gy-F0 group and 0 Gy-F0 group 10-11 weeks after radiation(P>0.05).There were no significant differences in body weight,testicular morphology,or sperm concentration of F1 generation mice between the 3 Gy-F1 group and the 0 Gy-F1 group(all P>0.05).However,compared with the 0 Gy-F1 group,the contents of LH,FSH and T in the 3 Gy-F1 group were all decreased(all P<0.05),the testicle volume,total sperm motility rate,forward motility rate and the fertility were considerably decreased(all P<0.05).DNA methylation sequencing showed that more differentially methylated genes were enriched in the pathway regulating microtubule formation.MassARRAY methylation sites analysis showed that the methylation level of Mid1 was significantly increased(P<0.05 or P<0.01).Mid1 was verified down-regulated in Fl and F0 sperm by qPCR(P<0.05 or P<0.01).However,there were no significant differences in volume of testes,testicular index,sperm concentration,sperm motility,hormone levels or Mid1 expression level between 0 Gy-F2 and 3 Gy-F2 mice in F2 generation male mice(all P>0.05).Conclusion Sperm damage in mice caused by ionizing radiation at a dose of 3 Gy can recover by itself.However,it may decrease sperm activity by regulating Mid1 methylation level of sperm in F1 mice,thus affect the fertility of F1 mice,but has no effect on the fertility of male F2 mice.
2.Celecoxib improves right heart function in mice after acute high-altitude hypoxia exposure by increasing 12,13-diHOME level
Wei ZHANG ; Xinyu BAO ; Xiaoyue LAI ; Xiaoqin WAN ; Yan TAN ; Hongjun YIN ; Xiaoshi CAI ; Dingyuan TIAN ; Ziyang WANG ; Pan ZHENG ; Fang DENG ; Zhihui ZHANG
Journal of Army Medical University 2025;47(19):2289-2301
Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.
3.Study on improvement mechanism of caudatin on liver injury in rats
Zhihui CHANG ; Yang BU ; Qian LIU ; Qian MA ; Jie SONG ; E SUN ; Yingjie WEI ; Yi LUO ; Xiaobin TAN
China Pharmacy 2023;34(5):531-536
OBJECTIVE To investigate the improvement mechanism of caudatin on liver injury of rats. METHODS SD rats were randomly divided into blank group, model group, caudatin low-dose and high-dose groups (25, 50 mg/kg), with 6 rats in each group. Diethylnitrosamine (DEN) was injected intraperitoneally three times per week for eight weeks to establish liver injury model of rats. At 5th week of modeling, the rats received relevant medicine or 0.5% sodium carboxymethylcellulose intragastrically for 4 weeks. The levels of liver function indexes [alanine transaminase (ALT), aspartate transaminase (AST), total protein (TP) and total bilirubin (TBI)] and inflammatory factors [interleukin (IL-6), tumor necrosis factor α (TNF-α), IL-1β] in serum were detected; the histopathological morphological changes of rat liver were observed; the positive protein expressions of nuclear factor κB (NF-κB) and 78 kDa glucose regulatory protein (Grp78) in liver tissue were also determined; the expressions of endoplasmic reticulum stress-related protein Grp78, C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6) and inositol requiring enzyme 1α (IRE1α) and the level of protein kinase R-like endoplasmic reticulum kinase robertluoyi@126.com (PERK) in liver tissue were detected. RESULTS Compared with blank group, serum levels of ALT, AST, TBI, IL-6, TNF-α and IL-1β and positive expressions of NF-κB and Grp78 in liver tissue as well as protein expressions of Grp78, CHOP, ATF6 and IRE1α, PERK protein phosphorylation level were all increased significantly in model group (P<0.05), while the serum level of TP was decreased significantly (P<0.05). The disordered structure of liver lobule, swollen liver cells, unclear intercellular boundary were observed and accompanied by inflammatory cell infiltration. Compared with model group, most of the above indexes were significantly reversed in caudatin groups (P<0.05); the structure of hepatic lobule was relatively complete and clear, the cells were arranged orderly, and the infiltration of inflammatory cells was also reduced. CONCLUSIONS Caudatin has a significant improvement effect against DEN-induced liver injury in rats, the mechanism of which may be associated with inhibiting endoplasmic reticulum stress and inflammatory reaction.
4.Effects of stepwise nursing in postoperative rehabilitation of patients with spinal cord injury
Shina CHENG ; Hongna MA ; Haiyang QIAO ; Chunhong PU ; Xiaowei JIA ; Zhenzhen LI ; Xiaoling WANG ; Zhihui WANG ; Lu TAN
Chinese Journal of Modern Nursing 2022;28(27):3802-3805
Objective:To explore the effect of stepwise nursing in postoperative rehabilitation of patients with spinal cord injury.Methods:From January 2020 to June 2021, convenience sampling was used to select 91 patients with spinal cord injury admitted to the Henan Third Provincial People's Hospital as the research object. The patients were divided into the observation group ( n=46) and the control group ( n=45) by random number table method. The control group received routine nursing, while the observation group received stepwise nursing on the basis of the control group. The postoperative functional independence and quality of life were compared between the two groups. Results:After six months of intervention, the scores of the Spinal Cord Independence Measure Ⅲ and the scores of each dimension of the Generic Quality of Life Inventory 74 in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Stepwise nursing can promote postoperative functional recovery and improve the quality of life of patients with spinal cord injury.
5.Status of iodine nutrition in pregnant women in Foshan City, Guangdong Province in 2017
Chunhui GU ; Qiang TAN ; Mao WANG ; Zhihui LIAO ; Guanbin GU ; Ruolin HE ; Guoqiang ZHONG
Chinese Journal of Endemiology 2019;38(1):65-67
Objective To study the iodine nutritional status of pregnant women in Foshan City,Guangdong Province,and to provide basis for iodine supplementation scientifically for them.Methods In 2017,five districts Chancheng,Nanhai,Shunde,Sanshui and Gaoming in Foshan were selected.Each monitoring site was divided into five sections according to stratified random sampling in five directions:east,west,south,north and middle.One township (street) was taken in each section,and 20 pregnant women were taken from each township (street) to detected their family salt iodine and urinary iodine levels.Results A total of 500 edible salt samples were collected from the families of pregnant women,the median of salt iodine was 24.8 mg/kg,the qualified iodized salt consumption rate was 95.8% (479/500),and the iodized salt coverage rate was 99.0% (495/500).There was a statistically significant difference in the iodine content of edible salt of pregnant women in diffierent districts (H =26.9,P < 0.05).A total of 500 urine samples were collected from pregnant women,the median of urinary iodine was 138.9 μg/L.There was a statistically significant difference in the levels of urinary iodine content of pregnant women in different districts (H =14.5,P < 0.05).There was no statistically significant difference in urinary iodine of pregnant women during different stages of pregnancy (H =2.6,P > 0.05).Conclusions The iodine intake for pregnant women is in a state of deficiency (< 150 μg/L) in Foshan of Guangdong Province.It is necessary to further strengthen the health education of key populations,and improve the iodine nutritional status of pregnant women.
6. Screening and influencing factors analysis for nutritional status in hospitalized children with pectus excavatum
Hui WANG ; Wei LIU ; Zhihui SU ; Jinhui WU ; Jing SUN ; Fenghua WANG ; Jianhua LIANG ; Jing WANG ; Meizhen TAN ; Huimin XIA
Chinese Journal of Applied Clinical Pediatrics 2019;34(18):1415-1417
Objective:
To screen the hospitalized children with pectus excavatum for nutritional status, and to analyze the influencing factors of nutritional status, then to provide the scientific basis for comprehensive management of clinical nutrition.
Methods:
The body mass index (BMI) of 360 hospitalized children with pectus excavatum in Guangzhou Women and Children′s Medical Center from January 2013 to December 2017 were reviewed and compared with World Health Organization standard and the emaciation rate was calculated.The influencing factors such as CT index, age, weight, height, sex, the width of thorax and surgical treatment were analyzed with BMI.
Results:
Compared with the lowest standard of BMI, the whole emaciation rate of hospitalized children with pectus excavatum was 93.61% (337/360 cases): in which severe, moderate and slight emaciation were 74.17% (267/360 cases), 13.33% (48/360 cases), and 6.11% (22/360 cases), respectively.BMI was negatively related with CT index (
7.Efficacy analysis of porcine small intestine submucosa-derived mesh and polypropylene mesh applied in anterior abdominal wall incisional hernia repair
Weigang DAI ; Zhihui CHEN ; Jinfu TAN ; Yujie YUAN ; Jidong ZUO ; Qiongyun ZHAO ; Min TAN
Chinese Journal of Digestive Surgery 2018;17(11):1095-1100
Objective To investigate the clinical efficacy of porcine small intestine submucosa-derived (SIS) mesh and polypropylene (PP) mesh applied in anterior abdominal wall incisional hernia repair.Methods The retrospective cohort study was conducted.The clinical data of 59 patients who underwent anterior abdominal wall incisional hernia repair in the First Affiliated Hospital of Sun Yat-Sen University between January 2012 and December 2017 were collected.Of 59 patients,22 undergoing anterior abdominal wall incisional hernia repair with SIS mesh and 37 undergoing anterior abdominal wall incisional hernia repair with PP mesh were respectively allocated into the SIS group and PP group.Surgeons selected surgical procedures according to hernia ring situations of patients.Observation indicators:(l) intra-and post-operative recovery situations;(2) follow-up.Follow-up using outpatient examination and telephone interview was performed to detect long-term complications of patients including foreign body sensation or pain in abdominal wall and hernia recurrence up to May 2018.Measurement data with normal distribution were represented as (x)±s,and comparison between groups was done using t test.Measurement data with skewed distribution were described as M (range),and comparison between groups was done using Mann-Whitney U test.Comparison of count data was analyzed using the chi-square test or Fisher exact probability.Results (1) Intra-and post-operative recovery situations:patients of the SIS group and PP group underwent successfully anterior abdominal wall incisional hernia repair.There were 2,3,3,14 and 5,26,1,5 patients undergoing open Onlay repair,open Sublay repair,laparoscopic intraperitoneal onlay mesh repair,laparoscopic combined with open mesh repair in the SIS group and PP group respectively.The volume of intraoperative blood loss,cases of postoperative incisional seroma and surgical site infection were (23± 11)mL,7,5 in the SIS group and (30± 13)mL,3,1 in the PP group respectively,with statistically significant differences between groups (t=-2.238,P<0.05).(2) Follow-up:patients of the SIS group and PP group were respectively followed up for 29.3 months (6.0-66.0 months) and 31.0 months (7.0-76.0 months),with no statistically significant difference between groups (Z =-1.388,P>0.05).During the follow-up,foreign body sensation or pain in abdominal wall and hernia recurrence were detected in 6,6 patients in the SIS group and 4,2 patients in the PP group respectively,with a statistically significant difference in hernia recurrence between groups (P<0.05) and with no statistically significant difference in foreign body sensation or pain in abdominal wall between groups (P>0.05).Conclusion Compared with polypropylene mesh,anterior abdominal wall incisional hernia repair using SIS mesh has higher incidence rate of postoperative incisional seroma,surgical site infection and hernia recurrence,but fewer volume of intraoperative blood loss.
8.The apoptotic inducing effect of deguelin on SH-SY5Y cells
Bijuan WU ; Zhihui JIANG ; Jingwen SUN ; Cuiwen TAN ; Yulin FAN ; Xiaoyan DING ; Xinyi SHANGGUAN ; Xinrong WU
Chinese Pharmacological Bulletin 2017;33(8):1136-1140
Aim To study the apoptotic inducing effects of deguelin on SH-SY5Y cells.Methods SH-SY5Y cells were treated with 0,0.625,1.25,2.5,5,10 and 20 μmol·L-1 deguelin for different time(24,48,72 h);cell viability was detected by CCK-8 assay.SH-SY5Y cells were treated with 0,8,20,50 μmol·L-1 deguelin for 24 h;light microscope and AO/EB double stained method were employed for observing the morphology and apoptotic morphology of treated cells.Apoptotic rate of treated cells was determined by flow cytometry.Cells were stained by DCFH-DA,and the whole reactive oxygen species(ROS)was determined by flow cytometry.Spectrophotometry was employed to determine the activation degree of caspase-3.Results Deguelin inhibited cell growth in a time-and dose-dependent manner,and the IC50 value of deguelin was(26.07±2.18),(18.33±0.94),(12.5±1.49)μmol·L-1 when treated with 24,48,72 h respectively.After treated with 8,20,50 μmol·L-1 deguelin for 24 h,cell apoptotic rate,ROS and activation rate of caspase-3 increased markedly(P<0.05),all of which performed a dose related effect.Conclusion Deguelin can inhibit SH-SY5Y cell proliferation and induce cell apoptosis,and the mechanism may be concerned with the elevated ROS and activated caspase-3.
9.Analysis of clinical diagnosis of 3315 cases with pulmonary tuberculosis suspicious symptoms transferred by non-tuberculosis control institutions
Zhiqiang LIANG ; Tao SONG ; Yumei LIU ; Xiaoyan LI ; Guobiao LIU ; Xiaoying WU ; Huixian ZHOU ; Yanbin ZHANG ; Shouyong TAN ; Zhihui LIU
The Journal of Practical Medicine 2017;33(15):2505-2508
Objective To study the level of clinical diagnosis of pulmonary tuberculosis and implementa-tion of tuberculosis prevention and control policy. Methods Frequencies and percentages of pulmonary tuberculosis, other lung diseases and health among 3315 cases with pulmonary tuberculosis suspicious symptoms ,transferred by non-tuberculosis control institutions during 2010-2015,were calculated and analyzed. Results Among the 3315 suspected cases of pulmonary tuberculosis ,cases of pulmonary tuberculosis ,tuberculosis ,other lung diseases and healthy group were 2068,598 and 649 based on final diagnosis and their percentages were 62.38%,18.04% and 19.58% respectively. As to groups of elder than fifteen years ,the proportion of patients with pulmonary tubercu-losis accounts for 72.62%,61.00%and 48.58% of the total of young group(15~44 years old ),middle age group (45 ~ 64 years old)and elderly group(≥ 65 years old )respectively. Conclusions Compared with pulmonary tuberculosis suspicious symptomscases from tuberculosis control institution during the same period ,the proportion of tuberculosis patients from transferred groups is roughly the same.It indicate high levels of tuberculosis diagnosis and implementation to tuberculosis control policy.
10.The pulmonary arterial hypertension of patients on maintained hemodialysis is positively associated with the decreased percent of CD8 T cell in the peripheral blood independently
Rongyi CHEN ; Fangfang XIANG ; Jiachang HU ; Xuesen CAO ; Yi FANG ; Bo SHEN ; Zhonghua LIU ; Wenlyu LYU ; Xiao TAN ; Zhihui LU ; Xiaoqiang DING ; Jianzhou ZOU
Chinese Journal of Nephrology 2017;33(5):342-348
Objective To explore the risk factors of pulmonary artery hypertension (PAH) and the its relationship with T cell subsets to provide a foundation for the prevention and treatment of PAH.Methods 154 maintained hemodialysis (MHD) patients in our dialysis center were recruited according to the criterion and divided into two groups subsequently:PAH group (pulmonary artery systolic pressure,PASP > 35 mmHg) and non-PAH group (PASP≤35 mmHg).The related clinical,biochemical and ultrasonic cardiogram data were collected and peripheral blood was acquired to detect the expressions of the surface antigen CD3,CD4,CD8 and CD69 with flow cytometry.Logistic regression analysis was used to find out the relationship between PAH and T cell subsets.Results There was no significant difference between 56 cases of PAH and 98 cases of non-PAH as regards gender,age,mean systolic and diastolic pressure,dialysis durations,morbidities of hypertension and diabetes,smoking rate,and left ventricular diameter.Compared with the non-PAH group,the PAH group demonstrated a lower percent of CD8 T cells and CD8 CD69 T cells,but a much higher left atrial diameter (LAD),Interventricular septum thickness,left ventricular posterior wall thickness,and NT-proBNP.The percentage of T cells,CD4 T cells and CD4 CD69 T cells showed no difference between the two groups.Multivariate analysis confirmed that PAH was negatively independently associated with the percentage of CD8 T cells and CD8CD69 T cells.Conclusions The decreased percentage of CD8 T cells and CD8CD69 T cells in the peripheral blood is a risk factor of PAH in maintained hemodialysis patients,and CD8 T cells may play an important role in the genesis of PAH.

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