Mismatch repair deficiency and abnormal p53 expression has significant predictive value for progesterone resistance and endometrial tumorigenesis in patients with endometrial atypical hyperplasia receiving fertility-preserving treatment.

OBJECTIVE: This study aimed to evaluate the prognostic ability of mismatch repair deficiency (MMR-d) and abnormal p53 expression (p53abn) in patients with endometrial atypical hyperplasia (EAH) who underwent fertility-preserving treatment. METHODS: This retrospective study evaluated 51 patients with EAH who underwent fertility-sparing treatment. Endometrial biopsy specimens obtained before hormone therapy were collected and used for immunohistochemical staining for MMR and p53 proteins. Response, relapse, and progression rates were assessed based on age, body mass index, diabetes, polycystic ovary syndrome, reproductive history, MMR status, and p53 status. RESULTS: Overall, 11/51 (21.6%) patients had loss of MMR proteins and 6/51 (11.8%) had p53abn. Patients with MMR-d had lower complete response (CR) rates than those with normal staining patients at 12 months after initial treatment (p = 0.049). Patients with MMR-d had significantly higher relapse rates than those with MMR-p at the 1-year follow-ups after achieving CR (p = 0.035). Moreover, patients with MMR-d had a higher incidence of disease progression at 2, 3, and 4 years after fertility-sparing treatment (p = 0.001, p = 0.01 and p = 0.035, respectively). Patients with p53abn had higher relapse rates than those with p53wt at the 1- and 2-year follow-ups after achieving CR (p = 0.047 and p = 0.036, respectively). Moreover, patients with p53abn had a higher incidence of disease progression at 3 and 4 years after fertility-sparing treatment (p = 0.02 and p = 0.049, respectively). CONCLUSIONS: EAH patients with MMR-d and p53abn have a significantly higher risk of disease relapse and progression. Thus, MMR-d and p53abn may be used as predictive biomarkers of progestin resistance and endometrial tumorigenesis in EAH.

Inhibition of USP7 suppresses advanced glycation end-induced cell cycle arrest and senescence of human umbilical vein endothelial cells through ubiquitination of p53.

Diabetes mellitus is a n arising public health concern, and diabetic foot is one of the most common complications of diabetes. Current management for diabetic foot cannot reach optimal remission. In this study, we aim to explore the mechanism underlying the pathogenesis of diabetic foot and provide novel strategies for the treatment of diabetic foot. A total of 10 normal skin tissues and 20 diabetic foot ulcer specimens are collected. Cell proliferation is determined by CCK-8 assay. Cell cycle is determined by flow cytometry, and cell senescence is evaluated by ß-galactosidase staining. Co-immunoprecipitation assay is used to explore the interaction between USP7 and p53. Advanced glycation end products (AGEs) are used to establish diabetic cell model, and streptozotocin (STZ) is used to establish diabetic rat model. Our results showed that USP7 expression is increased in diabetic foot ulcer and in human umbilical vein endothelial cells (HUVECs) after treatment with AGEs. Inhibition of USP7 can reduce cell cycle arrest and cell senescence in HUVECs. Moreover, USP7 can interact with p53 and promote its expression through mediating its deubiquitination. Knockdown of p53 can reverse USP7-mediated cell cycle arrest and cell senescence in HUVECs. In diabetic rats, HBX 41108, the specific inhibitor of USP7, can significantly accelerate wound healing. Our study reveals that the inhibition of USP7 can suppress AGEs-induced cell cycle arrest and cell senescence of HUVECs through promoting p53 ubiquitination. USP7 is a potential target for the treatment of diabetic foot ulcers.

Midterm results of coronary artery bypass graft surgery after synchronous or staged carotid revascularization.

OBJECTIVE: In the absence of randomized trials, the optimal approach to managing coexisting severe carotid and coronary diseases remains controversial. The aim of this study was to present the midterm follow-up results of patients who received a coronary artery bypass graft (CABG) after carotid revascularization and to compare the risk-adjusted outcomes of two approaches to carotid revascularization in the CABG population in a single center. METHODS: From January 2011 to December 2016, 245 patients underwent carotid revascularization within 90 days before CABG in Fuwai Hospital, including 32 who received combined carotid endarterectomy (CEA) and CABG (CEA-CABG), 208 who received staged carotid artery stenting (CAS) before CABG (CAS before CABG), and 5 who underwent a hybrid procedure of carotid stenting and coronary surgery (combined CAS-CABG). The primary composite end points were all-cause death, stroke, and myocardial infarction (MI). Therefore, the multivariable logistic regression analyses and propensity score-adjusted multiphase hazard function model were used to analyze the association between the types of revascularization, complications, and risk-adjusted mortality. RESULTS: One patient (3.13%) died 6 months after the CABG surgery in the combined CEA-CABG group. In the staged CAS group, 9 patients (4.33%) died after CABG surgery, including 3, 2, and 4 patients who died within 30 days, 1 year, and after 1 year (mean time after CABG surgery, 39 months; adjusted odds ratio [OR], 2.188; 95% confidence interval [CI], 0.251-19.093; P = .479), respectively. Stroke was observed in three patients (9.38%) in the combined CEA group and in 12 patients (5.77%) in the staged CAS group (OR, 0.625; 95% CI, 0.133-2.935; P = .552). The rates of MI were 6.25% and 7.21% for the combined and staged groups, respectively (adjusted OR, 1.249; 95% CI, 0.250-6.324; P = .787). In addition, composite events occurred in five (15.63%) and 33 patients (15.87%) in the combined and staged groups, respectively (adjusted OR, 1.362, 95% CI, 0.455-4.077; P = .581). No statistically significant differences were observed in the overall midterm incidences of mortality, stroke, MI, and composite events. CONCLUSIONS: Carotid revascularization is a safe and effective treatment for patients with concomitant carotid and cardiac disease. Combined CEA-CABG and staged CAS-CABG are associated with similar risks of mortality, stroke, or MI in the midterm outcomes.

[Analysis of urine cadmium and blood cadmium of workers before and after the cadmium dust control].

OBJECTIVE: To analyze the urinary cadmium, blood cadmium and urinary beta2-MG of workers in a zinc powder processing plant before and after the cadmium dust control, and to explore the effects of dust control on the prevention and treatment of cadmium hazards. METHODS: The on-site occupational hazard survey was used to investigate the changes of urine cadmium, blood cadmium and beta3-MG of 84 workers exposed to cadmium before and after the treatment by self-control analysis for evaluating the effects of dust control measures in a zinc powder processing plant. RESULTS: After treatment of the cadmium dust, the geometric mean of zinc dust in the workplace significantly decreased from 3.38 mg/m3 to 2.22 mg/m3 (P < 0.01). The geometric mean concentration of blood cadmium [(2.19 +/- 1.19) microg/L] and urine cadmium [(1.96 +/- 0.74) microg/g Cr] before treatment were significantly higher than those of one year [(1.63 +/- 0.83) microg/L] and [(1.25 +/- 0.83) microg/g Cr] and two years [(1.36 +/- 0.95) microg/L] and [(0.94 +/- 0.72) microg/g Cr] after the cadmium dust control (P < 0.01), respectively. The positive correlations analysis between urine cadmium and blood cadmium concentration of one and two years before and after the cadmium dust treatment implied that there was significant difference (r = 0.466, P < 0.01). CONCLUSION: Dust treatment could reduce the impact of low concentration cadmium on the urine cadmium and blood cadmium concentrations of the workers exposed to cadmium, and effectively prevent the cadmium poisoning.