The histone acetyltransferase TIP60 regulates the DNA damage response following genotoxic stress by acetylating histone and remodeling chromatin. However, the molecular mechanisms underlying the TIP60-dependent response to UV-induced DNA damage remain poorly understood. To systematically analyse proteins that regulate TIP60 activity in response to UV irradiation, we performed a proteomic analysis of proteins selectively bound to TIP60 in response to UV irradiation using mass spectrometry and identified a novel regulatory mechanism by which TIP60 orchestrates transcriptional activation of p53-dependent checkpoint response in UV-irradiated cells. The initial step of this pathway involves UV-induced association of TIP60 with SUMO-conjugation enzymes and site-specific sumoylation of TIP60 at lysines 430 and 451 via Ubc9. This sumoylation initiates the relocation of TIP60 from nucleoplasm to the promyelocytic leukemia body, which is essential for the UV-irradiated DNA damage repair response via a p53-dependent pathway. Significantly, inhibition of TIP60 sumoylation by overexpression of non-sumoylatable mutant abrogates the p53-dependent DNA damage response, demonstrating the importance of TIP60 sumoylation in response to UV irradiation. Our biochemical characterization demonstrated that the sumoylation of TIP60 augments its acetyltransferase activity in vitro and in vivo. Thus, this study shed new light on the function and regulation of TIP60 activity in UV-irradiated DNA damage response.

BackgroundThyroid nodules are a common clinical problem and some are potentially cancerous; however, little is known about the prevalence of thyroid nodules in China. The objective of this study was to investigate the prevalence of thyroid nodules in a healthy Chinese population.MethodsWe reviewed electronic medical records of 13,178,313 participants from 30 provinces and regions who received health examinations and underwent thyroid ultrasound at Meinian Onehealth Healthcare in 2017. Among them, 6,192,357 were excluded based on predefined criteria. All thyroid nodules were diagnosed by ultrasonography, and standardized protocols were adopted for data collection, quality control, and data management.ResultsA total of 6,985,956 participants (mean age: 42.1 ± 13.1 years) were included in this study. The overall prevalence of thyroid nodules was 36.9% (95% CI, 35.7%–38.1%; age- and sex-standardized prevalence 38.0% [95% CI, 37.0%–39.1%]). The prevalence of thyroid nodules in females (44.7% [95% CI, 43.4%–45.9%], age-standardized prevalence: 45.2% [95% CI, 44.1%–46.4%]) was significantly higher than that in males (29.9% [95% CI, 28.8%–31.0%], age-standardized prevalence 31.2% [95% CI, 30.1%–32.2%]; P < 0.001). The prevalence of thyroid nodules decreased from <18 to 25 years, while increased with age over 25 years old. The top three provinces with the highest prevalence of thyroid nodules were Jilin (47.6%), Liaoning (44.8%), and Shandong (43.9%), whereas Guizhou (23.9%), Chongqing (26.2%), and Shaanxi (26.4%) had the lowest prevalence. Females had more than 10% higher rates of thyroid nodules than males in all included provinces and regions, except for Tianjin (8.0%). Based on the geographical regions of China, the northeast had the highest prevalence (46.8% [95% CI, 44.1%–49.2%]), whereas northwest had the lowest prevalence (28.9% [95% CI, 26.9%–31.6%]. Based on multivariable logistic regression analysis, factors including age, gender, body mass index, systolic blood pressure, diastolic blood pressure, uric acid, fasting blood glucose, triglycerides, high-density lipoproteins, and low-density lipoproteins were significantly associated with the presence of thyroid nodules.ConclusionThis study provides the first nationwide analysis of the prevalence of thyroid nodules in China. Our results showed that the prevalence of thyroid nodules was high in health screening Chinese people with regional-specific patterns.

The relationships between all-cause mortality and serum intact parathyroid hormone (iPTH), calcium, and phosphate are fairly diverse in patients on maintenance hemodialysis according to prior studies. This study evaluated the association of chronic kidney disease-mineral and bone disorder (CKD-MBD) markers with all-cause mortality in prevalent hemodialysis patients from 2007 to 2012 in Beijing, China. A cohort, involving 8530 prevalent hemodialysis patients who had undergone a 6–70 months follow-up program (with median as 40 months) was formed. Related data was recorded from the database in 120 hemodialysis centers of Beijing Health Bureau (2007 to 2012). Information regarding baseline demographics, blood CKD-MBD markers and all-cause mortality was retrospectively reviewed. By using multivariate Cox regression model analysis, patients with a low iPTH level at baseline were found to have greater risk of mortality (<75pg/ml, HR = 1.36, 95% confidence interval (CI) 1.16–1.60) than those with a baseline iPTH level within 150–300 pg/ml. Similarly, death risk showed an increase when the baseline serum calcium presented a low level (<2.1mmol/L, HR = 1.54; 95% CI 1.37–1.74). Levels of baseline serum phosphorus were not associated with the risk of death. Similar results appeared through the baseline competing risks regression analysis. Patients with a lower level of serum iPTH or calcium are at a higher risk of all-cause mortality compared with those within the range recommended by Kidney Disease Outcome Quality Initiative (KDOQI) guidelines.

FSRP plays an important role in detecting asymptomatic intracranial artery stenosis.

ObjectiveTo investigate the distribution characteristics of intraocular pressure (IOP) by sex, age, and geographic location in China and to build the corresponding reference intervals (RIs).Material and methodsA cross-sectional, multi-centered, population-based study was conducted. All data were collected from participants without eye diseases who underwent ophthalmological examinations in 170 Health Screening Centers in mainland China in 2018. The non-contact tonometer was used to measure IOP. The age-, sex-, and province-specific RIs of IOP were investigated. The IOP of different age–sex groups was further explored by stratifying according to height, body mass index (BMI), blood pressure, altitude, and geographic area.ResultsDuring the study, a population-based sample of 284,937 participants was included. The distribution of measured IOP followed an approximately Gaussian distribution, with a higher mean value in men than in women. The IOP showed a general trend of decline with age for both men and women and varied across geographical locations. The mean IOP was 15.4 (95% CI: 9.1-21.6) mmHg for men and 14.9 (95% CI: 9.0-20.8) mmHg for women. For men, it decreased from 11.0-23.5 mmHg at age 18-24 years to 10.5-20.5 mmHg at age ≥70 years. For women, it decreased from 10.5-22.0 to mmHg at age 18-24 years to 10.0-21.0 mm Hg at age ≥70 years.ConclusionsThe IOP varied with age, sex, metabolic disorders and geographic location. These RIs should be considered in the clinical process of glaucoma diagnosis and treatment.