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.

Deficiencies remain in the early identification and screening method for type 2 diabetes mellitus(T2DM).Relying solely on blood glucose indicators as diagnostic criteria fails to capture the systematic evolution of glucose metabolism destabilization and does not allow for the identification of the critical transition period preceding the onset of T2DM.In the complex system of the human body,structural and state variables correspond to the traditional Chinese medicine concepts of"zang"and"xiang."These variables determine the landscape of the systemic state changes over time.The pathogenesis of T2DM is characterized by a shift from compensatory insulin secretion to β-cell dysfunction,driven by negative-positive feedback dynamics,ultimately resulting in a marked increase in blood glucose levels.A critical transition exists between glycemic homeostasis and the establishment of T2DM disease homeostasis.Using theoretical approaches such as critical slowing and dynamic network markers in dynamical systems theory,various clinical case data-including four-diagnosis information,multiple biological samples,and histological analysis method-can be leveraged to identify the critical transition key stage from pre-disease to disease of T2DM,facilitating early intervention.This paper aims to develop a dynamic model describing the transition from"glucose homeostasis-glycemic state of instability-steady state of T2DM"by analyzing the mechanism of the complex human system and the dynamic characteristics underlying T2DM onset.This framework aims to enhance early identification method.Establishing this holistic approach offers a novel perspective for the prevention and treatment of T2DM.

Severe intra-abdominal infections are life-threatening conditions and a significant challenge for surgeons. This article presents a case of an elderly patient with a severe intra-abdominal infection complicated by an anastomotic leak. This patient had experienced prolonged sepsis and multiple surgical traumas. Upon admission to our department, exploratory surgery revealed extensive bowel edema and adhesions, an anastomotic leak, and abdominal contamination with infection. In accordance with the principles of damage control surgery, the anastomotic leak was exteriorized, the abdomen was left open, and continuous intra-abdominal lavage with dual-lumen catheters was implemented to effectively control the infection. Negative pressure wound therapy was used to manage the open abdomen, and a negative pressure-assisted drainage device was used to manage the enteroatmospheric fistula. After granulation of the abdominal wound, split-thickness skin grafting was performed. The enteroatmospheric fistula was converted into an enterocutaneous fistula. A 3D-printed stoma baseplate was used to manage the digestive fistula. Concurrently, enhanced parenteral and enteral nutritional support was provided. Six months later, the patient successfully underwent definitive fistula resection and abdominal wall defect repair.

Objective:To evaluate the efficacy of vacuum sealing drainage (VSD) in the comprehensive management of full-thickness perineal wound dehiscence following pelvic exenteration (PE).Methods:This study employed a descriptive case series design. We retrospectively analyzed the clinical data of 29 patients who developed postoperative perineal wound infections with full-thickness dehiscence after PE. These cases included 16 patients from the Department of General Surgery at Jiangyin People's Hospital (Jiangsu Province) and 13 patients from the Department of Colorectal Surgery at the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital). VSD was applied to manage the dehisced wounds, with outcomes assessed based on wound healing time, complications, and follow-up data.Results:A total of 29 patients were included in the study. The operative time for PE was (498 ± 83) minutes. Among them, 23 patients underwent combined sacrococcygeal resection. The median number of VSD devices used was 28 (22, 39). The postoperative perineal wound healing time was 95 (82, 110) days in patients who underwent combined sacrococcygeal resection, 74 (63, 89) days in those without sacrococcygeal resection, 93 (79, 102) days in those treated with simple pelvic-abdominal isolation using a biological basement membrane mesh and 76 (60, 91) days in those who received combined pelvic packing with a pedicled omental flap. All patients uniformly developed Clavien-Dindo grade III complications at 2 weeks postoperatively, manifesting as perineal wound infection and dehiscence, which were successfully managed with VSD therapy. Subsequent evaluation identified delayed (>30 days) grade III complications, including enterocutaneous (3 cases) and urinary (2 cases) fistulae, all requiring surgical revision. All patients completed the follow-up at 6 months postoperatively. Three patients still presented with minimal exudate from the perineal wound, which resolved after standardized wound care and packing with alginate silver ion dressings. Four cases (13.8%) developed stoma high-output syndrome, which improved after oral medication. Eight patients (27.6%) developed adhesive intestinal obstruction, which improved with conservative treatment.Conclusions:VSD demonstrates unique advantages in managing complex wounds. For full-thickness perineal wound dehiscence after PE, VSD is a safe and effective therapeutic strategy.

Deficiencies remain in the early identification and screening method for type 2 diabetes mellitus(T2DM).Relying solely on blood glucose indicators as diagnostic criteria fails to capture the systematic evolution of glucose metabolism destabilization and does not allow for the identification of the critical transition period preceding the onset of T2DM.In the complex system of the human body,structural and state variables correspond to the traditional Chinese medicine concepts of"zang"and"xiang."These variables determine the landscape of the systemic state changes over time.The pathogenesis of T2DM is characterized by a shift from compensatory insulin secretion to β-cell dysfunction,driven by negative-positive feedback dynamics,ultimately resulting in a marked increase in blood glucose levels.A critical transition exists between glycemic homeostasis and the establishment of T2DM disease homeostasis.Using theoretical approaches such as critical slowing and dynamic network markers in dynamical systems theory,various clinical case data-including four-diagnosis information,multiple biological samples,and histological analysis method-can be leveraged to identify the critical transition key stage from pre-disease to disease of T2DM,facilitating early intervention.This paper aims to develop a dynamic model describing the transition from"glucose homeostasis-glycemic state of instability-steady state of T2DM"by analyzing the mechanism of the complex human system and the dynamic characteristics underlying T2DM onset.This framework aims to enhance early identification method.Establishing this holistic approach offers a novel perspective for the prevention and treatment of T2DM.

Severe intra-abdominal infections are life-threatening conditions and a significant challenge for surgeons. This article presents a case of an elderly patient with a severe intra-abdominal infection complicated by an anastomotic leak. This patient had experienced prolonged sepsis and multiple surgical traumas. Upon admission to our department, exploratory surgery revealed extensive bowel edema and adhesions, an anastomotic leak, and abdominal contamination with infection. In accordance with the principles of damage control surgery, the anastomotic leak was exteriorized, the abdomen was left open, and continuous intra-abdominal lavage with dual-lumen catheters was implemented to effectively control the infection. Negative pressure wound therapy was used to manage the open abdomen, and a negative pressure-assisted drainage device was used to manage the enteroatmospheric fistula. After granulation of the abdominal wound, split-thickness skin grafting was performed. The enteroatmospheric fistula was converted into an enterocutaneous fistula. A 3D-printed stoma baseplate was used to manage the digestive fistula. Concurrently, enhanced parenteral and enteral nutritional support was provided. Six months later, the patient successfully underwent definitive fistula resection and abdominal wall defect repair.

Objective:To evaluate the efficacy of vacuum sealing drainage (VSD) in the comprehensive management of full-thickness perineal wound dehiscence following pelvic exenteration (PE).Methods:This study employed a descriptive case series design. We retrospectively analyzed the clinical data of 29 patients who developed postoperative perineal wound infections with full-thickness dehiscence after PE. These cases included 16 patients from the Department of General Surgery at Jiangyin People's Hospital (Jiangsu Province) and 13 patients from the Department of Colorectal Surgery at the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital). VSD was applied to manage the dehisced wounds, with outcomes assessed based on wound healing time, complications, and follow-up data.Results:A total of 29 patients were included in the study. The operative time for PE was (498 ± 83) minutes. Among them, 23 patients underwent combined sacrococcygeal resection. The median number of VSD devices used was 28 (22, 39). The postoperative perineal wound healing time was 95 (82, 110) days in patients who underwent combined sacrococcygeal resection, 74 (63, 89) days in those without sacrococcygeal resection, 93 (79, 102) days in those treated with simple pelvic-abdominal isolation using a biological basement membrane mesh and 76 (60, 91) days in those who received combined pelvic packing with a pedicled omental flap. All patients uniformly developed Clavien-Dindo grade III complications at 2 weeks postoperatively, manifesting as perineal wound infection and dehiscence, which were successfully managed with VSD therapy. Subsequent evaluation identified delayed (>30 days) grade III complications, including enterocutaneous (3 cases) and urinary (2 cases) fistulae, all requiring surgical revision. All patients completed the follow-up at 6 months postoperatively. Three patients still presented with minimal exudate from the perineal wound, which resolved after standardized wound care and packing with alginate silver ion dressings. Four cases (13.8%) developed stoma high-output syndrome, which improved after oral medication. Eight patients (27.6%) developed adhesive intestinal obstruction, which improved with conservative treatment.Conclusions:VSD demonstrates unique advantages in managing complex wounds. For full-thickness perineal wound dehiscence after PE, VSD is a safe and effective therapeutic strategy.

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 .