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.

Objective To investigate the relationship between frailty and serum biomarkers in the elderly. Methods A total of 371 elderly individuals aged 60 years and above with complete medical data were recruited during health examinations. Frailty phenotype assessment and comprehensive geriatric assessment were conducted.Serum levels of interleukin-6 (IL-6 ) ,high sensitivity C-reactive protein(hs-CRP) ,tumor necrosis factor-α(TNF-α) ,homocysteine(Hcy) ,insulin-like growth factor-1(IGF-1) ,25-hydroxyvitamin D[25(OH)D] ,folic acid and vitamin B12(VitB12) were detected by enzyme-linked immunosorbent assays ( ELISA ) and chemiluminescence immunoassays. Associations between frailty and the above factors were analyzed. Results Serum levels of IL-6 ,TNF-α ,Hcy and IGF-1 were significantly elevated along with progressive increase in frailty severity(all P＜0.05).There were a downward trend in serum 25(OH)D levels and an upward trend in serum hs-CRP ,folic acid and VitB12 levels as frailty severity increased ,but the changes did not amount to any statistical significance(all P＞0.05).Logistic regression analysis showed that ,after adjusting for age ,gender ,body mass index (BMI)and some clinical aspects (hearing loss ,urinary incontinence ,pain ,malnutrition ,cognitive dysfunction ,decreased activities of daily living ,depression , insomnia ,and anemia) ,serum levels of IL-6(OR=1.012 ,95% CI=1.005-2.041 ,P=0.033) ,IGF-1 (OR= 1.017 ,95% CI = 1.011-1.118 ,P= 0.021)and Hcy (OR= 1.007 ,95% CI :1.002-1.073 ,P=0.047)were significantly associated with frailty status. Conclusions Serum levels of IL-6 ,Hcy and IGF-1 are related to frailty status and may be used as potential biomarkers for the assessment of frailty in older adults.

Objective To evaluate the feasibility and clinical efficacy of retroperitoneal laparoscopic partial nephrectomy (RLPN) with individual operation plan in treatment of small renal cell carcinoma (RCC). Methods 98 patients with small RCC who was treated by RLPN from June 2012 to June 2016 were retrospectively analyzed. There were 57 males and 41 females with a mean age of 52 years old (ranging 28 ~ 75 years old). 52 cases were located on the right side while 46 cases were left. The mean tumor size was 3.1 cm in diameter (ranging 0.8 ~ 4.5 cm). 87 patients (A group) were underwent standard RLPN with clamping main renal artery. 7 patients (B group) with exophytic RCC were performed without clamping renal artery, but with separating main renal artery and prepared for possible clamping. 4 patients (C group) with endophytic RCC were performed with clamping renal artery under ultrosound monitoring. The feasibility and outcomes were evaluated by surgical and oncological outcomes. Results 84 cases among A group were underwent standard RLPN successfully, with 2 cases converted to open surgery and 1 case failed to excising tumor completely and converted to laparoscopic radical nephrectomy. The amount of bleeding during operation was 30 ~ 350 ml, average 93 ml, operation time was 70 ~ 245 min, average 127 min, warm ischemia time 20 ~ 42 min, average 26 min. 6 cases among B group were performed successfully without clamping renal artery with 1 case converted to clamp renal artery for 15 min during the operation because of obvious bleeding. The amount of bleeding was 160 ~ 380 ml, average 220 ml, operation time was 85 ~ 215 min, average143 min. 4 cases of C group were all performed successfully, The amount of bleeding was 35 ~ 250 ml, average 85 ml, operation time was 110 ~ 235 min, average 175 min, warm ischemia time 25 ~ 40 min, average 28 min. With a mean follow up of 28 months (ranging 18 ~ 42 months), there was only 1 case of A group occured local recurrence and lung metastases and accepted molecular targeted therapy with Sorafenib. Conclusion RLPN with individual operation plan in treatment of small RCC is safe and effective, the long-term effect of the procedure needs further investigation.

People do have some risks of exposing to the radiation during their daily life .Longtime or megadose ionizing radiation can induce tissue damage ,which is related to cell apoptosis ,necrosis and inflammation ,etc ..Currently ,more and more radio protective agents were developed and several signaling pathways were involved .NFκB ,MAPK ,PI3k/Akt ,p53 and STAT3 signaling pathways were reviewed in this article .