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.

Objective:b> To explore the difference in intensive care unit (ICU) readmission rate between high dependency unit (HDU) and general ward for the patients with severe liver disease (SLD), and reflect the effect of HDU on SLD patientse. Methods:b> A clinical cohort of patients transferred out of ICU was established, and patients with severe liver disease who were transferred to HDU& general ward from July 2017 to December 2021 in the intensive care Unit of the Fifth Medical Center of PLA General Hospital were continuously enrolled. The main liver function indexes and MELD scores between the two groups were compared. Analyze the differences in severity and ICU readmission rate of SLD patients transferred to different wards, and clarify the role of HDU in the management of SLD patient. Area under the receiver operating characteristic (AUROC) was used to investigate the value of MELD score in predicting the occurrence of return to ICU. Results:b> The level of INR, TB, ALT and MELD scores of SLD patients transferred to HDU were significantly higher than those of patients transferred to general ward (all P < 0.05). MELD > 17 was found in 70.7% of SLD patients transferred to HDU group, while MELD ≤ 17 was found in 61.9% of SLD patients in general ward group. The ICU readmission rate of all patients in this cohort was 11.4%. By MELD quartile stratification, patients with SLD whose MELD > 23 had a significantly higher ICU readmission rate (20.0%) than those with SLD whose MELD ≤ 23 (8.6%) (P = 0.020). The ICU readmission rate was 8.2% when MELD ≤ 23 in the HDU group and 9.1% when MELD > 23, showing no significant difference (P = 1.000). The ICU readmission rate was 8.8% when MELD ≤ 23 in the general ward group. ICU reentry rate increased significantly to 36.4% when MELD > 23 (P = 0.001). MELD Score predicts that the optimal cut-off value of SLD patients in general ward readmitted to ICU was 23.5. Conclusion:b> The high dependency unit could better admit patients with SLD who were transferred out of ICU and required step-down treatment, and significantly reduced the ICU readmission rate of patients with SLD who were transferred out of ICU with MELD > 23. The patients with SLD and MELD score > 23 are suitable to be transferred from ICU to HDU.

<b>Objective:b> To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. <b>Methods:b> This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. <b>Results:b> Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). <b>Conclusions:b> The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.
Male ; Female ; Humans ; Prognosis ; Neoplasm Staging ; Retrospective Studies ; Nomograms ; Lymph Nodes/pathology* ; Risk Factors ; Colonic Neoplasms/surgery*

Humans ; Lung ; Pneumoconiosis/diagnostic imaging* ; Radiography ; Tomography, X-Ray Computed

Background/Aims: Gastroparesis is identified as a subject that is understudied in Asia. The scientific committee of the Asian Neurogastroenterology and Motility Association performed a Knowledge, Attitude, and Practices survey on gastroparesis among doctors in Asia. Methods: The questionnaire was created and developed through a literature review of current gastroparesis works of literature by the scientific committee of Asian Neurogastroenterology and Motility Association. Results: A total of 490 doctors from across Asia (including Bangladesh, China, Hong Kong, Indonesia, Japan, Malaysia, Myanmar, the Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam) participated in the survey. Gastroparesis is a significant gastrointestinal condition. However, a substantial proportion of respondents was unable to give the correct definition and accurate diagnostic test. The main reason for lack of interest in diagnosing gastroparesis was “the lack of reliable diagnostic tests” (46.8%) or “a lack of effective treatment” (41.5%). Only 41.7% of respondents had access to gastric emptying scintigraphy. Most doctors had never diagnosed gastroparesis at all (25.2%) or diagnosed fewer than 5 patients a year (52.1%). Conclusions Gastroparesis can be challenging to diagnose due to the lack of instrument, standardized method, and paucity of research data on normative value, risk factors, and treatment studies in Asian patients. Future strategies should concentrate on how to disseminate the latest knowledge of gastroparesis in Asia. In particular, there is an urgent need to estimate the magnitude of the problems in high risk and idiopathic patients as well as a standardized diagnostic procedure in Asia.

To understand the mutational characteristics of ATP7B gene of hepatolenticular degeneration in Xinjiang region. 24 cases were diagnosed as hepatolenticular degeneration and the exon of ATP7B gene was detected in some of their siblings and parents. A total of 45 ATP7B gene mutations (93.75%) were detected in 24 cases, of which 14 cases were homozygous mutations or compound heterozygous mutations, six cases were heterozygous mutations and four cases were no mutations. A total of 24 gene mutations and 14 SNPS were detected, including 8 new mutations: c.251C > A, c.121A > c, c.2945C > A, c.2194C > T, c.2947T > c, c.3626T > A, c.3662_3664del, c.3557G > T. The most common mutations were c.2621C > T (p.A874V) [16.7% (4/24)] and c.2333G > T (p.R778L) [12.5% ​​(3/24)]. A total of 4 cases were diagnosed as pre-symptomatic. In this study, the most common mutation in the ATP7B gene is A874V. The most common genetic mutations in Han and Uyghur patients were different. The most common mutation in Han and Uyghur patients is R778L and A874V. Exon 11 is the gene mutations hot spot for patients with hepatolenticular degeneration in Xinjiang region, and is one of the priority exons to be detected when screening patients with suspected hepatolenticular degeneration.

<b>Objective:b> To describe the genetic structure of populations in different areas of China, and explore the effects of different strategies to control the confounding factors of the genetic structure in cohort studies. <b>Methods:b> By using the genome-wide association study (GWAS) on data of 4 500 samples from 10 areas of the China Kadoorie Biobank (CKB), we performed principal components analysis to extract the first and second principal components of the samples for the component two-dimensional diagram generation, and then compared them with the source of sample area to analyze the characteristics of genetic structure of the samples from different areas of China. Based on the CKB cohort data, a simulation data set with cluster sample characteristics such as genetic structure differences and extensive kinship was generated; and the effects of different analysis strategies including traditional analysis scheme and mixed linear model on the inflation factor (λ) were evaluated. <b>Results:b> There were significant genetic structure differences in different areas of China. Distribution of the principal components of the population genetic structure was basically consistent with the geographical distribution of the project area. The first principal component corresponds to the latitude of different areas, and the second principal component corresponds to the longitude of different areas. The generated simulation data showed high false positive rate (λ=1.16), even if the principal components of the genetic structure was adjusted or the area specific subgroup analysis was performed, λ could not be effectively controlled (λ>1.05); while, by using a mixed linear model adjusting for the kinship matrix, λ was effectively controlled regardless of whether the genetic structure principal component was further adjusted (λ=0.99). <b>Conclusions:b> There were large differences in genetic structure among populations in different areas of China. In molecular epidemiology studies, bias caused by population genetic structure needs to be carefully treated. For large cohort data with complex genetic structure and extensive kinship, it is necessary to use a mixed linear model for association analysis.
China ; Genetic Structures ; Genome-Wide Association Study ; Humans ; Linear Models ; Principal Component Analysis

<b>Objective:b> To explore the relationship between different dimensions of infectious disease-specific health literacy scale in China. <b>Methods:b> Structural equation model (SEM) was employed to assess the psychometric properties of the infectious disease-specific health literacy scale. Based on the database from a randomly selected sample of 4 499 adult residents in three provinces in China, from March to May 2015. AMOS 21.0 software was used to build the SEM for data analyses. <b>Results:b> SEM analyses showed a good model fit of data, with the following satisfied parameters: goodness-of-fit index was 0.969, adjusted goodness-of-fit index was 0.962, root mean square residual was 0.038, root mean square error of approximation was 0.038, standardized root mean square residual was 0.032, Tacker-Lewis index/non-normed fit index was 0.926, comparative fit index was 0.934, normed fit index was 0.925, relative fit index was 0.915, incremental fit index was 0.934, parsimony goodness-of-fit index was 0.782, parsimony-adjusted normed fit index was 0.817, parsimony-adjusted comparative fit index was 0.825 and critical N was 702. The established SEM showed that the total influence path coefficient of "infectious disease-related knowledge and values" on the "infectious disease prevention" , "management or treatment of infectious diseases" and "identification of infection sources" were 0.771, 0.744 and 0.843, respectively. The total influence path coefficients of "identification of infection sources" , "infectious disease prevention" on "management or treatment of infectious diseases" were 0.164 and 0.535, respectively. The effect of "infectious disease-related knowledge and values" on "management or treatment of infectious diseases" appeared the greatest (55.4%), followed by "infectious disease prevention" (28.6%) and "identification of infection sources" (2.7%). <b>Conclusion:b> This SEM could be optimistically used for planning and evaluation of health education and promotion programs on infectious diseases prevention.
Adult ; China ; Health Literacy ; Humans ; Models, Theoretical ; Psychometrics ; Surveys and Questionnaires

<b>Objective:b> To study the modification effect of age on the association between body mass index and the risk of hypertension. <b>Methods:b> 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. <b>Results:b> 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). <b>Conclusion:b> 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

<b>Objective:b> To explore the survival factors and construct a prognostic index (PI) for oral squamous cell carcinoma (OSCC). <b>Methods:b> From January 2004 to June 2016, a total of 634 patients with pathologically confirmed OSCC were recruited in a hospital of Fujian. The clinical and follow-up data of all the patients with pathologically confirmed OSCC were collected to identify the factors influencing the prognosis of OSCC. All the patients were randomly divided into two groups: modeling group (modeling dataset, n=318) and validation group (validation dataset, n=316). Randomization was carried out by using computer-generated random numbers. In the modeling dataset, survival rates were calculated using Kaplan-Meier method and compared using the log-rank test. Cox regression model was used to estimate the hazard ratio (HRs) and 95% confidence intervals (CIs) of prognosis factors. An PI for OSCC patients prognostic prediction model was developed based on β value of each significant variable obtained from the multivariate Cox regression model. Using the tertile analysis, patients were divided into high-risk group, moderate-risk group, and low-risk group according to the PI, the Akaike information criterion (AIC) and Harrell's c-statistic (C index) were used to evaluated the model's predictability. <b>Results:b> Results from the multivariate Cox regression model indicated that aged ≥55 years (HR=2.22, 95%CI: 1.45-3.39), poor oral hygiene (HR=2.12, 95%CI: 1.27-3.54), first diagnosis of lymph node metastasis (HR=5.78, 95%CI: 3.60-9.27), TNM stage Ⅲ-Ⅳ (stage Ⅰ as reference) (HR=2.43, 95%CI: 1.10-5.37) and poor differentiation (well differentiation as reference) (HR=2.53, 95%CI: 1.60-4.01) were the risk factors influencing the prognosis of OSCC. The PI model had a high predictability in modeling group and validation group (AIC and C index were 1 205.80, 0.700 2 and 1 150.47, 0.737 3). <b>Conclusion:b> Age, poor oral hygiene, first diagnosis of lymph node metastasis, TNM stage and histological grade were factors associated with the prognosis of OSCC, and the PI model has a certain significance in the clinical treatment of OSCC.
Carcinoma, Squamous Cell/therapy* ; China/epidemiology* ; Humans ; Lymphatic Metastasis ; Middle Aged ; Mouth Neoplasms/therapy* ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Survival Rate ; Treatment Outcome