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.

Background::Due to the wide variety of morphology, size, and dynamics, selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation (PPVI). This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional (3D)-printed models for planning PPVI with the Venus P-valve. Methods::Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University.Results::3D model bench testing altered treatment strategy in all patients (100%). One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly. In the remaining 14 patients, valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery. In four patients, it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract (RVOT) ( n = 2) or risk of compression coronary artery ( n = 2). Concerning sizing, we found that an oversize of 2-5 mm suffices. Anchoring of the valve was dictated by the flaring of the in- and outflow portion in the pulmonary artery. PPVI was successful in all 14 patients (absence of valve migration, no coronary compression, and none-to-mild residual pulmonary regurgitation [PR]). The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group (36 [2] vs. 32 [4], Z = -3.77, P <0.001). Conclusions::In vitro testing indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique, as 2-5 mm sufficed.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an ¹⁸F-labeled MAGL inhibitor ([¹⁸F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [¹⁸F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl₄) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [¹⁸F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [¹⁸F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [¹⁸F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [¹⁸F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.

With the widely application of the metagenomics, the relationship between microbiota and disease has become a hot research topic. Understanding the potential association between upper gastrointestinal cancer or precancerous lesions and microbiota may play an important role in the early detection, clinical diagnosis and treatment, and prognostic evaluation of upper gastrointestinal cancer. Therefore, a literature retrieval was conducted by using PubMed, Embase and wanfang databases to summarize the latest research progress in the microbiota of upper gastrointestinal cancer, including oral, esophageal, gastric cancer and precancerous lesions. Lower microbial diversity or richness in esophageal cancer and precancerous lesions and specific prognostic biomarkers for esophageal cancer were found. Lactobacillus richness showed an increase trend during the process from gastritis to gastric cancer. This paper summarizes the progress in the research of potential biological etiology of upper gastrointestinal cancer from the perspective of metagenomics in order to provide evidence on the, prevention and control of upper gastrointestinal cancer.
Esophageal Neoplasms/microbiology* ; Gastrointestinal Microbiome ; Gastrointestinal Neoplasms/microbiology* ; Gastrointestinal Tract/microbiology* ; Humans ; Lactobacillus ; Metagenomics/trends* ; Microbiota ; Precancerous Conditions/microbiology* ; Prognosis ; Research/trends* ; Risk Factors ; Stomach Neoplasms/microbiology*

Objective: To explore the interaction effect between mother's educational level and preschoolers' dietary pattern on attention-deficit/hyperactivity disorder (ADHD). Methods: In 2014, there were 16 439 children aged 3-6 years old from 91 kindergartens in Ma'anshan municipality of China. A semi-quantitative food frequency questionnaire and the 10-item Chinese version of the Conners' Abbreviated Symptom Questionnaire (C-ASQ) were administered to assess the usual dietary intake and symptoms on ADHD. Social-demographic information was collected through questionnaires. Unconditional logistic regression was used to analyze the multiplication interaction effect between mother's educational level and preschoolers' dietary pattern on ADHD. Excel software was used to analyze the additive interaction effect of mother's educational level and preschoolers'dietary pattern on ADHD. Results: Results showed that factors as: mother's low educational level[aOR=1.31 (1.13-1.52)], scores related to preschoolers in the top quintile of "food processing" [aOR=1.31 (1.16-1.48)] and "snack" [aOR=1.45 (1.29-1.63)]patterns showed greater odds while preschoolers in the top quintile of "vegetarian" [aOR=0.80 (0.71-0.90)]showed less odds for having ADHD symptoms. Both multiplication and additive interactions were observed between mothers with less education. The processed dietary patterns (OR=1.17, 95%CI: 1.11-1.25), relative excess risk of interaction (RERI), attributable proportion (AP) and the interaction index (SI) appeared as 0.21, 0.13 and 1.47, respectively. Multiplication interaction was observed between levels of mother's low education and the snack dietary pattern (OR=1.21, 95%CI: 1.14-1.29), with RERI, AP and SI as 0.49, 0.26 and 2.36, respectively. However, neither multiplication interaction or additive interaction was noticed between levels of mother's low education and the vegetarian dietary pattern (OR=0.97, 95%CI: 0.92-1.03), with RERI, AP and SI as 0.09, 0.05 and 1.15, respectively. Conclusions: Levels of mother's low education presented a risk factor for ADHD symptoms in preschool children. Both multiplication interaction and additive interaction were observed between mother's low education levels and the processed dietary pattern. Multiplication interaction was noticed between mother's education levels and the snack dietary pattern but not with the vegetarian dietary pattern.
Attention Deficit Disorder with Hyperactivity/epidemiology* ; Child ; Child Nutritional Physiological Phenomena ; Child, Preschool ; China ; Diet ; Educational Status ; Feeding Behavior ; Female ; Humans ; Logistic Models ; Mothers ; Risk Factors ; Surveys and Questionnaires

Objective: To analyze the epidemiological characteristics, dynamic trend of development and related influencing factors of hepatitis C in Shandong, China, 2007-2016, also to provide epidemiological evidence for prevention and control of HCV. Methods: National surveillance data of hepatitis C from 2007 to 2016 in Shandong was used, with distribution and clustering map of hepatitis C drawn at the county level. Panel Poisson regression was used to explore the influencing factors of hepatitis C at the city level. Results: The incidence of hepatitis C in Shandong increased from 1.49/100 000 in 2007 to 4.72/100 000 in 2016, with the high incidence mainly clustered in the urban regions in Jinan, Zibo, Weihai et al. and surrounding vicinities. Majority of the cases were young adults, with 53.16% (14 711/27 671) of them being farmers. Results from the Multiple panel Poisson regression analysis indicated that factors as: population density (aIRR=1.07, 95%CI: 1.05-1.10), number of hospital per hundred thousand people shared (aIRR=1.16, 95%CI: 1.08-1.24), expenditure of medical fee in rural (aIRR=1.21, 95%CI: 1.08-1.37) and the proportion of the tertiary industry (aIRR=1.08, 95%CI: 1.07-1.09) were all correlated to the incidence of hepatitis C. Conclusions: The incidence of hepatitis C had been increasing rapidly in recent years, in Shandong. Prevention and control of HCV should focus on high risk population. In addition, rural, especially in areas with lower economics provision should be under more attentions, so as to find more concealed cases for early treatment.
Adult ; China/epidemiology* ; Cities ; Hepacivirus ; Hepatitis C/prevention & control* ; Humans ; Incidence ; Population Surveillance ; Young Adult

Objective: To explore the spatio-temporal epidemic trends and related driving effects of meteorological factors on brucellosis in Datong city, Shanxi province, from 2005 to 2015. Methods: We collected the surveillance data on brucellosis and related meteorological data in Datong city from 2005 to 2015, to describe the epidemic characteristics of the disease. Quasi-Poisson distribution lag non-liner model (DLNM) was built to explore the driving effect of monthly meteorological data on the disease. Results: From 2005 to 2015, Datong city reported a total of 17 311 cases of brucellosis including one death, with the annual average incidence as 47.43 per 100 000 persons. A rising trend was seen during the study period. The monthly incidence of Brucellosis presented an obvious curve with a major peak from March to June, accounted for 48.40% of the total cases. The high incidence areas in the city gradually expanded from the northeast and southeast to the western areas. Results from the DLNM studies suggested that seasonality of brucellosis in Datong was significantly affected by metrological factors such as evaporation, rainfall and temperature. The peak of delayed effect appeared the highest when the monthly cumulative evaporation capacity was 140-260 mm and the monthly cumulative rainfall was 20-60 mm with lag less than 1 month or the monthly temperature was -13 ℃ with lag of 4-5 months. Conclusions: The incidence of human brucellosis in Datong city increased significantly from 2005 to 2015. Meteorological factors such as evaporation, rainfall, temperature all showed significant driving effects on the disease.
Brucellosis/epidemiology* ; China/epidemiology* ; Cities ; Climate ; Humans ; Incidence ; Meteorological Concepts ; Space-Time Clustering ; Spatio-Temporal Analysis ; Temperature

Objective: To explore the association between nuclear factor kappa-light-chain-enhancer of activated genetic polymorphisms in B cells (NF-κB) and the HCV susceptibility, among the Chinese population. Methods: A total of 1 679 participants were enrolled; including 503 drug users and 1 176 other participants at risk under the exposure for blood. By using the logistic regression analysis, related risk factors for HCV infection among subjects were analyzed. Two NF-κB pathway variants, NF-κB1 rs72696119 and REL rs13031237 were then genotyped by TaqMan assay method. Logistic regression analysis was performed to analyze the association between gene polymorphisms and the susceptibility on HCV. Results: Among the drug users, women (OR=0.408, 95%CI: 0.308-0.767) appeared to be associated with the decreased risk for HCV infection, while factors as drug injection (OR=8.817, 95%CI: 5.577-13.937) and the duration of drug-intake >5.5 years (OR=2.891, 95%CI: 1.824-4.583) were associated with the increased risk for HCV infection. Among the participants who had been exposed to blood, women (OR=3.431, 95%CI: 2.360-4.988) were associated with the increased risk for HCV infection, while the levels of education beyond elementary school (OR=0.613, 95%CI: 0.429-0.876) were associated with the decreased risk for HCV infection. Compared to the reference NF-κB1 rs72696119 CC genotype, the carriage of GG genotype was associated with an increased risk of susceptibility on HCV (OR=1.412, 95%CI: 1.035-1.927) among the total study population. Results from the interaction analysis showed that there was no interactive effects appeared between rs72696119 and route of infection, or between rs72696119 and gender among the total population under study (all P>0.05). Conclusion: NF-κB1 polymorphism rs72696119 and related factors seemed associated with the susceptibility to HCV infection among high-risk Chinese populations.
Asian People/genetics* ; B-Lymphocytes ; Case-Control Studies ; China/epidemiology* ; Female ; Genetic Predisposition to Disease ; Hepatitis C/genetics* ; Humans ; Male ; Middle Aged ; NF-kappa B/genetics* ; Polymorphism, Single Nucleotide

OBJECTIVETo assess the clinical efficacy on post-stroke shoulder-hand syndrome (SHS) treated with acupuncture and rehabilitation and the impacts on patients' nailfold microcirculation.

METHODSOne hundred and twenty patients were randomized into an acupuncture rehabilitation group and a simple rehabilitation group, 60 cases in each one. In the simple rehabilitation group, OT (comprehensive rehabilitation therapy) training was adopted. In the acupuncture rehabilitation group, on the basis of the treatment as the simple rehabilitation, acu puncture was added at Taiyuan (LU 9), Zusanli (ST 36), Xuanzhong (GB 39), Waiguan (TE 5), Shousanli (LI 10), Quchi (LI 11) and Jianyu (LI 15). Acupuncture was given once a day, 7 days made one session. Totally, 4 sessions of treatment were required. Fugl-Meyer score, upper limb pain score, the score of nerve function defect and the items of nailfold microcirculation of patients were assessed in the the two groups before and after treatment. The efficacy was compared between the two groups.

RESULTS(1) The upper limb pain, the systematic motor function of the upper limbs, the nerve function defect, nailfold microcirculation and clinical symptoms were all improved after treatment in either the acupuncture rehabilitation group or the simple rehabilitation group as compared with those before treatment, indicating the significant difference (P<0. 05, P<0. 01). (2) The im provements in the upper limb pain (0. 90+/-0.71 vs 1. 80+/-0. 66), the systematic motor function of the upper limbs (42. 43 13. 57 vs 29. 98+/-15. 11), the nerve function defect (8. 60+/-11. 61 vs 13. 0+/-1. 74), nailfold microcirculation (total score 3. 18+/-1.32 vs 4.34+/-1.23) and clinical symptoms in the acupuncture rehabilitation group after treatment were different significantly as compared with those in the simple rehabilitation group (PO0. 05,P-O. 01), and the results in the acupuncture rehabilitation group were superior to the simple rehabilitation group. (3) In the acupuncture rehabilitation group, the markedly effective rate was 50. 0% (30/60) and the total effective rate was 93.3% (56/60), which was better than 16.7% (10/60) and 63. 3% (38/60) respectively in the simple rehabilitation group (all P<0. 05).

CONCLUSIONBoth the combined therapy of acupuncture and rehabilitation and the simple rehabilitation training are effective in the treatment of post-stroke SHS, and promote the status of nailfold microcirculation, the efficacy of the combined therapy is better than that of the latter.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Female ; Humans ; Male ; Middle Aged ; Reflex Sympathetic Dystrophy ; etiology ; rehabilitation ; therapy ; Stroke ; complications ; Treatment Outcome