Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Hearing Loss, High-Frequency ; Hearing Loss, Noise-Induced/epidemiology* ; Humans ; Manufacturing Industry ; Noise, Occupational/adverse effects* ; Occupational Exposure

Hearing ; Hearing Loss, Noise-Induced/etiology* ; Humans ; Male ; Manufacturing Industry ; Noise, Occupational/adverse effects* ; Occupational Exposure/adverse effects* ; Surveys and Questionnaires

Humans ; Interior Design and Furnishings ; Manufacturing Industry ; Noise, Occupational ; Occupational Exposure ; Textile Industry

Objective: To understand the prevalence of hepatitis C virus (HCV) infection in 5 populations in China during 2016-2017 and provide evidence for the estimation of prevalence trend of hepatitis C and evaluation on the prevention and control effect. Methods: A total of 87 national sentinel surveillance sites for hepatitis C were set up in 31 provinces (autonomous regions and municipalities) of China to obtain the information about HCV infection prevalence in 5 populations, including volunteer blood donors, people receiving physical examination, patients receiving invasive diagnosis and treatment, patients receiving hemodialysis, and clients visiting family planning outpatient clinics. From April to June, 2016 and 2017, cross-sectional surveys were repeatedly conducted in the 5 populations and blood samples were collected from them for HCV antibody detection. Results: In 2016, 86 sentinel sites completed the surveillance (one sentinel site was not investigated), and 115 841 persons were surveyed. The overall HCV positive rate was 0.38% (442/115 841, 95%CI: 0.23%-0.53%). In 2017, all the 87 sentinel sites completed the surveillance, and 120 486 persons were surveyed. The overall HCV positive rate was 0.37% (449/120 486, 95%CI: 0.23%-0.52%). In 2016 and 2017, the anti-HCV positive rates were 4.46% (223/5 005, 95%CI: 2.18%-6.73%) and 4.39% (216/4 919, 95%CI: 2.29%-6.50%) respectively in hemodialysis patients, 0.85% (44/5 200, 95%CI: 0.27%-1.42%) and 0.70% (36/5 150, 95%CI: 0.15%-1.24%) respectively in patients receiving invasive diagnosis and treatment and remained to be ≤0.25% in volunteer blood donors, people receiving physical examination and clients visiting family planning outpatient clinics. Results for the comparison of the anti-HCV positive rates in the 5 populations indicated that the differences were significant (F=23.091, P<0.001 in 2016 and F=20.181, P<0.001 in 2017). Conclusions: Data from the sentinel surveillance of HCV infection on prevalence in China showed that the anti-HCV positive rates varied in the 5 populations during 2016-2017. The anti-HCV positive rate appeared the highest in the hemodialysis patients, followed by that in the patients receiving invasive diagnosis and treatment, and the prevalence of HCV infection in other 3 populations were at low levels.
China/epidemiology* ; Cross-Sectional Studies ; Hepacivirus ; Hepatitis C/epidemiology* ; Hepatitis C Antibodies ; Humans ; Prevalence ; Sentinel Surveillance

Objective: To analyze the burden of disease (BOD) on diabetes attributable to high BMI in China from 1990 to 2016. Methods: Data based on population of the 2016 Global Burden of Disease Study for China were used to analyze the attributable fractions (PAF) of BOD for diabetes attributable to high BMI. Measurements for attributable BOD of diabetes included disability adjusted life years (DALY), years of lost life (YLL), years living with disability (YLD), death number and mortality rate. The average world population from 2010 to 2035 was used as a reference. Results: In 2016, death number of diabetes attributable to high BMI was 40 310, which was significantly higher than that in 1990 (15 008). Age-standardized death rate of diabetes attributable to high BMI increased from 2.01/100 000 in 1990 to 2.60/100 000 in 2016, which showed a more significant increasing trend in both males and people aged 15-49 years. DALYs of diabetes attributable to high BMI increased from 1.09 million person years to 3.30 million person years. YLL and YLD also showed increasing trends. The highest increasing rate of YLD was in people aged 15-49 years. High BMI was responsible for 26.01% of the diabetes deaths in 2016 in China, an increase of 39.39% compared with that in 1990 (18.66%). Most provinces in China experienced a sharp increase of DALY of diabetes attributable to high BMI from 1990 to 2016. Inner Mongolia, Xinjiang, Zhejiang, Macao SAR, Sichuan and Qinghai had the most significant increase tendency in terms of DALY rate during this period. Conclusions: There was a rapid increase of the deaths and mortality rate of diabetes attributable to high BMI, causing a heavy disease burden, in China from 1990 to 2016. The BOD varied in both different age and gender groups. More attention should be paid to males and people aged 15-49 years in the prevention and control programs of diabetes.
Adolescent ; Adult ; Body Mass Index ; China/epidemiology* ; Cost of Illness ; Diabetes Mellitus/ethnology* ; Disabled Persons ; Humans ; Macau ; Male ; Middle Aged ; Quality-Adjusted Life Years ; Sickness Impact Profile ; Young Adult

Objective: To estimate the serotype and age-specific hospitalization burden associated with hand, foot and mouth disease (HFMD) in Anhua county of Hunan province, between October 2013 and September 2016. Methods: We collected hospitalization records of HFMD patients from 6 virological surveillance hospitals, and reimbursement records through new rural cooperative medical system from 23 township health centers to estimate the age-specific hospitalization burden of HFMD in Anhua. Combined with the results of virological surveillance, the serotype-specific hospitalization burden of HFMD in Anhua, was estimated. Results: During the three years, it was estimated that 3 541 clinical diagnosed HFMD cases, including 3 146 laboratory-confirmed HFMD cases, were hospitalized in Anhua, but only one was diaguosed as being severe. The estimated average hospitalization rate was 723/100 000(95%CI: 699/100 000-747/100 000) for clinical diagnosed HFMD and 642/100 000 (95%CI: 620/100 000-665/100 000) for laboratory-confirmed HFMD between October 2013 and September 2016. The cases caused by Cox A16 (208/100 000) and Cox A6 (202/100 000) had higher hospitalization rates compared with the cases caused by EV71 (130/100 000), Cox A10 (38/100 000) and other enterovirus (64/100 000), and the difference was statistically significant (P<0.001). HFMD-associated hospitalization rates peaked in children aged 1 year (3 845/100 000), and then decreased with age. Compared with the hospitalized HFMD caused by EV71 and Cox A16, Cox A6-associated hospitalizations mainly occurred in younger age groups (P<0.001). Conclusion: Our study revealed a substantial hospitalization burden associated with mild HFMD caused by EV71, Cox A16, Cox A6 and Cox A10, especially in young children, in Anhua.
Child ; China/epidemiology* ; Enterovirus ; Enterovirus A, Human/isolation & purification* ; Enterovirus Infections/virology* ; Hand, Foot and Mouth Disease/virology* ; Hospitalization/statistics & numerical data* ; Hospitals/statistics & numerical data* ; Humans ; Infant ; Serogroup

Objective: To investigate the association between maternal body height and risk of preterm birth. Methods: A total of 11 311 pregnant women who gave birth of live singletons were recruited from the Healthy Baby Cohort Study in Hubei province, China from September 2012 to October 2014. Finally 11 070 pregnant women were selected as study subjects. Data were collected by using questionnaires, their prenatal care records and medical records. The women were divided into 4 groups according to the quartiles distribution (<158 cm, 158- cm, 160- cm, and >164 cm). Gestational age was estimated according to maternal last menstrual time. Preterm birth was defined as delivering a live singleton infant at 28-37 weeks' gestational age. Logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the association between body height and preterm birth. Results: Among the 11 070 pregnant women, the incidence of preterm birth was 5.9%. Logistic regression analysis indicated that women in group with body height <158 cm had 46% (OR=1.46, 95%CI: 1.16-1.83) higher risk of giving preterm birth than those in group with body height >164 cm after adjustment for potential confounders. Every 1- cm increase in body height was associated with 3% lower risk of preterm birth (OR=0.97, 95%CI: 0.95-0.99). Conclusion: Shorter body height was a risk factor for preterm birth. It is necessary to strengthen the monitoring in pregnant women with short body height to reduce the risk of preterm birth.
Body Height ; China/epidemiology* ; Cohort Studies ; Female ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Odds Ratio ; Pregnancy ; Premature Birth/epidemiology* ; Prenatal Care ; Risk Factors

Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as <0.05, no positive sites would meet this standard. When DMC CpG site cg05684382, with the smallest P value (1.26E-06) as on chromosome 12, the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16. Conclusions: In this study, we analyzed the genome-wide DNA methylation and its correlation with obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr: 12) and cg26188191 (chr: 16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.
Adolescent ; Bayes Theorem ; Beijing ; Body Weight ; Child ; DNA Methylation/genetics* ; Epigenesis, Genetic ; Female ; Genome-Wide Association Study ; Humans ; Male ; Obesity/genetics* ; Twins, Monozygotic ; Waist Circumference

Objective: To study the modification effect of age on the association between body mass index and the risk of hypertension. Methods: People age ≥18 years old were selected by clusters, from a rural area of Henan province. In total, 20 194 people were recruited at baseline during 2007 and 2008, and the follow-up study was completed from 2013 to 2014. Logistic regression model was used to assess the risk of incident hypertension by baseline BMI and age-specific BMI. Results: During the 6-year follow-up period, 1 950 hypertensive persons were detected, including 784 men and 1 166 women, with cumulative incidence rates as 19.96%, 20.51%, and 19.61%, respectively. Compared with those whose BMI<22 kg/m(2), the RRs of hypertension were 1.09 (0.93-1.27), 1.17 (1.01-1.37), 1.34 (1.14-1.58) and 1.31 (1.09-1.56) for participants with BMI as 22-, 24-, 26- and ≥28 kg/m(2), respectively. In young and middle-aged populations, the risk of hypertension gradually increased with the rise of BMI (trend P<0.05). However, in the elderly, the increasing trend on the risk of hypertension risk was not as significantly obvious (trend P>0.05). Conclusion: The effect of BMI on the incidence of hypertension seemed to depend on age. Our findings suggested that a weight reduction program would be more effective on young or middle-aged populations, to prevent the development of hypertension.
Adolescent ; Age Factors ; Aged ; Asian People/statistics & numerical data* ; Body Mass Index ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Hypertension/ethnology* ; Incidence ; Logistic Models ; Male ; Middle Aged ; Risk Factors ; Rural Population