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.

Due to factors such as an aging population, the Hospital Authority(HA) of Hong Kong is facing a contradiction between limited health resource supply and continuously increasing demand. In order to effectively address challenges, the HA prompted three measures to bridging the demand-supply gap. The HA relied on its management system advantages to continuously increase its capital construction to enhance the service capacity of public health institutions; transformed service delivery mode so as to improve the experience, quality, and efficiency of service delivery; established cooperation with private service providers and communities to shunt population health demand. The practices of HA can provide reference for public hospitals and their sponsors in other regions of China.

Objective:To study the clinical features, diagnosis, treatment and genetic characteristics of neonatal-onset protein C deficiency (PCD).Methods:The clinical data of a newborn patient with severe PCD admitted to our neonatal department was reviewed. Databases including CNKI, Wanfang Database, CMB, VIP database, PubMed, Embase and SCI database were searched using" infantile", " neonate ", "newborn", "protein C deficiency" and "purpura fulminans" as key words. Published cases of PCD were analyzed.Results:The patient was a full-term female infant who developed multiple symptoms within 2 days after birth. The symptoms included thrombocytopenia, intracranial hemorrhage, purpura fulminans (PF), disseminated intravascular coagulation (DIC), celiac hemorrhage, hypertension, portal and iliac vein thrombosis, purulent meningitis and retinal detachment. Protein C activity was less than 10%. Genetic tests showed compound heterozygous mutations c.314G>T (p.c105f) of paternal origin and c.1218G>A (p.m406i) of maternal origin in PROC gene. According to ACMG guidelines, the mutations were strongly suspected pathogenic variants and consistent with an autosomal recessive (AR) inheritance pattern. The patient was discharged after 6 weeks of treatment at parents' request of withdrawal. A total of 25 articles on 29 patients with relatively complete clinical data were retrieved, including 18 males and 11 females. 4 patients were preterm and 25 full-term. 28 patients showed symptoms within 7 days after birth. The common clinical features were cutaneous PF and splanchnic thrombi. 22 cases documented protein C activity and ranged from 0 to 25%. 16 patients had PROC gene abnormalities and compound heterozygous mutations were found in 10 patients. Among the 22 patients with prognostic data, 11 died (9 within 3 months after birth), the remaining survivors suffered from sequelae including severe intellectual motor development disorder, epilepsy and blindness.Conclusions:The main clinical manifestations of neonatal-onset PCD include PF, DIC, multi-organ hemorrhage and thrombus. The disease is acute and severe, with rapid progression, poor prognosis and high fatality rate. Protein C activity and PROC gene testing may help establish the diagnosis.

Objective:To discuss the clinical characteristics and genetic diagnosis of fetal familial hemophagocytic lymphohistiocytosis (FHL).Methods:Clinical data of a case of fetal FHL from Children's Hospital, Capital Institute of Pediatrics was analyzed, and related FHL cases at home and abroad were retrieved from PubMed, CNKI, and Wanfang databases using terms including "fetus", "neonate", and "familial hemophagocytic lymphohistiocytosis", from the establishment of the database to January 3, 2021, to summarize the characteristics of this disease.Results:This index case was found with fetal splenomegaly, free fluid in the abdominal cavity, and enlargement of the ventricle at 39 +3 weeks of gestation, and presented with fever, tachypnea, hepatosplenomegaly, skin ecchymosis and petechia, and lymphadenectasis after birth. Laboratory examination revealed pancytopenia, abnormal liver function, elevated ferritin and triglyceride, and decreased fibrinogen levels. CD107a excitation experiment showed decreased degranulation function of NK cell (ΔCD107a<5%). Hemophagocytosis was observed in the bone marrow smear. Genomic DNA sequence analysis demonstrated compound heterozygous mutations of c.118-308C>T and c.3002T>C in the UNC13D gene. All the above findings led to the diagnosis of FHL3. Despite chemotherapy with dexamethasone and cyclosporin, and symptomatic treatment after admission without hematopoietic stem cell transplantation, the baby died on day 52. A total of 15 papers related to fetal FHL, including 20 infants, were retrieved. Among these 21 cases (including the index case), the main clinical symptoms were fetal edema and hepatosplenomegaly, which may be accompanied by fetal distress and increased amniotic fluid volume, and postnatal fever, dyspnea, rash, and central nervous system involvement. Laboratory and imaging examination results were consistent with the diagnostic criteria for hemophagocytic hyperplasia. As far as we know, the reported fetal FHL gene mutations were PRF1 (FHL2) and UNC13D gene mutation (FHL3), in which reduced expression of perforin and granzyme can be detected, respectively. Dexamethasone, cyclosporin, etoposide, and other chemotherapy and symptomatic treatment are the primary treatments currently, and alternative therapies include intrauterine chemotherapy in the third trimester and postnatal hematopoietic stem cell transplantation. Among the 21 cases, including the index case, intrauterine death occurred in four cases, 13 children died at different times after birth, and only four children survived, among which the eldest one was 12 years old. Conclusions:FHL is a condition with atypical early signs, high mortality rate and treatment difficulties. Fetal FHL should be considered in differential diagnosis in fetuses with edema or hepatosplenomegaly besides hemolysis, infection, autoimmune diseases, and hereditary problems. Therefore, with immunotechnology and gene sequencing, early diagnosis and treatment can be prompted to improve the prognosis of this group of population.

Retraction Note to: J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2019 20(3):238-252. https://doi.org/10.1631/jzus.B1800122. The authors have retracted this article (Guo et al., 2019) because some data from the original literature had not been converted to appropriate units in the paper, which resulted in deviation of the meta-analysis results. For example, for the forest plot used to examine associations between PM exposure and the risk of adverse birth outcomes, the estimates from Brauer et al. (2008), Pedersen et al. (2013), Zhao et al. (2015), and Hansen et al. (2006) were on the originally reported scales of 1 µg/m, 10 µg/m, 10 µg/m, and Inter Quartile Range, respectively. None of these estimates had been converted to 20 µg/m increase scale that was stated in the article. Similar problem exists in the analysis on associations between NO exposure and risk of adverse birth outcomes. Therefore, the results of the meta-analysis are misleading. All authors have agreed to this retraction and express their deepest apologies to the original authors, publishers, and readers.

Objective:To study the respiratory morbidity and the risk factors of respiratory complications in late-preterm infants.Methods:The data of 959 late-preterm infants in 21 hospitals in Beijing from October 2015 to April 2016 were collected.These infants were divided into the respiratory morbidity group (237 cases) and the control group (722 cases) according to whether they had short-term respiratory morbidity after birth.Clinical data of the two groups were compared.Results:Among the 959 late-preterm babies, 530 were male and 429 were female.Two hundred and thirty-seven cases (24.7%) developed short-term respiratory morbidity after birth.Infectious pneumonia developed in the most cases (81 cases, 8.4%), followed by transient tachypnea (65 cases, 6.8%), amniotic fluid aspiration (51 cases, 5.3%), and respiratory distress syndrome (24 cases, 2.5%) successively.All the infants recovered and discharged.There were no differences between gender and maternal age between 2 groups (all P>0.05). Compared with the control group, more late-preterm infants were delivered by cesarean section (73.4% vs.59.7%, χ2=14.43, P<0.001) and the 1-minute Apgar score was lower [(9.41±1.66) scores vs.(9.83±0.53) scores, t=5.40, P<0.001] in the respiratory morbidity group.The differences were statistically significant.There were more cases with maternal complications in the respiratory morbidity group that in the control group (66.7% vs.58.6%, χ2=4.877, P=0.027), but no difference in various complications between 2 groups was observed ( P>0.05). In the respiratory morbidity group, the most frequent complications were maternal hypertension and preeclampsia (27.8% vs.22.6%, χ2=2.728, P=0.099). There were no differences between 2 groups in gestational age, birth weight and birth length (all P>0.05). There were more infants small for gestational age and large for gestational age in the respiratory morbidity group than in the control group (18.8% vs.14.1%, 6.3% vs.2.4%, χ2=8.960, P=0.011). The duration of hospitalization of the respiratory morbidity group was significantly longer than that of the control group [(9.00±4.42) d vs.(6.82±4.19) d, t=6.676, P<0.001] since the infants with respiratory morbidity needed to be hospita-lized. Conclusions:Respiratory diseases occur in about 1/4 of late-preterm infants.Infants who are delivered by cesarean section and whose mothers are complicated with the maternal hypertension and preeclampsia should be monitored closely.Respiratory support should be provided for infants not appropriate for gestational age who are more likely to suffer from respiratory diseases, so that they can successfully pass through the transition period.

Objective: To analyze the prognostic value of CD7 expression in newly diagnosed acute myeloid leukemia (AML) patients, and to further explore the correlation between CD7 expression and CEBPA mutation, and to clarify the prognostic value of CD7(+) in AML patients with wild-type (WT) or mutant-type (MT) CEBPA. Methods: The clinical data of 298 newly diagnosed non-M(3) AML patients between January 2010 and December 2016 were analyzed retrospectively. The clinical characteristics and prognosis of CD7(+) and CD7(-) patients were respectively compared in all patients, and in patients with WT and MT CEBPA. The relationship between CD7 expression and CEBPA mutation was determined by chi-square, and the effects of CEBPA mutation on survival and prognosis in CD7(+) group by Kaplan-Meier method. Results: In CD7(+) group, the frequencies of CEBPA mutation were 10.1% (single site) and 33.9% (double site) , significantly higher than those of the CD7(-) group (5.3% and 4.2%) (P=0.000) . Subgroup prognostic analysis showed a lower CR rate (P=0.001) and a higher RR (P=0.023) in CD7(+) group comparing to those of CD7(-) group in AML patients with wild type CEBPA. There were no statistical difference between CD7(+) group and CD7(-) group in overall survival (OS) and disease free survival (P>0.05) , while in the CEBPA mutant group the CD7(+) group has higher OS (P=0.019) and DFS (P=0.010) . Based on the CD7 expression and CEBPA mutation, 298 cases were divided into 3 subgroups, named as CD7(+)-CEBPA MT group, CD7(-) and CD7(+)-CEBPA WT group. The 3-year OS of the 3 groups were 80.2%, 48.0% and 30.6%, respectively (P<0.001) , and the 3-year DFS were 74.1%, 37.4% and 22.2%, respectively (P<0.001) . Conclusion: The CEBPA mutation rate was higher in CD7(+) AML patients then that of CD7(-) patients. CD7 expression has opposite prognostic significance in AML patients carrying the wild-type or mutant-type CEBPA. Based on CD7 expression and CEBPA mutation, a new risk stratification model can be established, which is helpful to guide the clinical individualized treatment for AML patients.
CCAAT-Enhancer-Binding Proteins/genetics* ; Disease-Free Survival ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, CONCLUSIONS Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.
Beijing/epidemiology* ; Breast Feeding ; China/epidemiology* ; Communicable Diseases/epidemiology* ; Female ; Hospitalization ; Hospitals ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Male ; Pregnancy

Several reviews have assessed the relationship between exposure to ambient air pollution and adverse birth outcomes during pregnancy, but the results remain controversial. The objective of this study was to assess this correlation quantitatively and to explore sources of heterogeneity. We included all published case-control or cohort studies that evaluated the correlation between ambient air pollution and low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA). Analytical methods and inclusion criteria were provided on the PROSPERO website (CRD42018085816). We evaluated pooled effects and heterogeneity. Subgroup analyses (grouped by exposure period, study settings, study design, exposure types, data source, Newcastle-Ottawa quality score (NOS), and adjustment for smoking or meteorological factors) were also conducted and publication bias was examined. The risk of bias in systematic reviews (ROBIS) tool was used to evaluate the overall risk of bias in this review. Forty studies met the inclusion criteria. We observed pooled odds ratios (ORs) of 1.03-1.21 for LBW and 0.97-1.06 for PTB when mothers were exposed to CO, NO₂, NO_x, O₃, PM_2.5, PM₁₀, or SO₂ throughout their pregnancy. For SGA, the pooled estimate was 1.02 in relation to NO₂ concentrations. Subgroup analysis and sensitivity analysis decreased the heterogeneity to some extent, such as the subgroups of continuous measures (OR=0.98 (0.97-0.99), I²=0.0%) and NOS>7 (OR=0.98 (0.97-0.99), I²=0.0%) in evaluating the association between PTB and NO₂. This review was completed with a low risk of bias. High concentrations of air pollution were significantly related to the higher risk of adverse birth outcomes. However, the sources of heterogeneity among studies should be further explored.
Air Pollutants/adverse effects* ; Air Pollution/adverse effects* ; Bias ; Environmental Exposure ; Female ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Infant, Small for Gestational Age ; Maternal Exposure ; Odds Ratio ; Pregnancy ; Pregnancy Outcome ; Premature Birth/epidemiology* ; Risk Assessment

Objective TodiscusstheevaluationeffectivenessofADCofMR DWIinneoadjuvantchemotherapy (NAC).Methods ThirtyGninepatientswithlocallyadvancedbreastcancerwereenrolledinthisstudy.Allthesepatientswerediagnosedbypuncture biopsyandtreatedwithNAC.DWIwasperformedbeforechemotherapyandafter4cyclesofchemotherapyrespectively.Radicalresectionof breastcancerwasperformedwithinoneweekaftertheendof4cyclesofNAC.Accordingtotheclinicalefficacyorpathologicalresponse,the changesoftumorvolumeandtumorcelldensitybeforeandafterchemotherapyweremeasured.Theresponseoftumorwasdividedas clinicallyeffective,completeremission (CR)+partialremission(PR)andclinicalineffectiveness,stabilizationdisease(SD)+progression disease(PD)ormajorhistologicalresponse (MHR)andnonGmajorhistologicalresponse (NMHR),respectively.Toevaluatethe practicalutilityofneoadjuvantchemotherapy,theADCvaluesweremeasuredinallgroupsandanalyzedstatistically.Results Before NAC,therewasnosignificantdifferenceinADCvaluebetweenCR+PR (0.96±0.22)andSD+PD (0.93±0.14)orMHR (1.05±0.22), NMHR (0.99±0.14).TheratiosofCR+PRand MHR were56.4%and66.7%respectivelyattheendoftreatment,andtheADC valuesinallpatientswerehigherthanthatbeforechemotherapy.However,Therewasnosignificantdifferencebeforeandafterchemotherapy intheSD+PD (1.02±0.19)andNMHR (1.08±0.20)groups (P＞0.05),whileCR+PR (1.47±0.16)and MHR (1.62+0.13) groupsweresignificantlydifferentbeforeandafterchemotherapy(P＜0.05).Therateoftumorvolumechangewaspositivelycorrelated withΔADC (r＝0.539,P＜0.05).Conclusion TheADCvalue canbeusedtoevaluatethevolumeandpathologicalgradeof tumorafterNACbasedon MRIplainscananddynamicscan, whichishelpfulfortimelyandeffectivepredictiveevaluationof chemotherapyeffect.ADCvaluecanbeusedasearlyevaluationofNACforbreastcancerandprognosticindicators.