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: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

OBJECTIVE To investigate the application value of narrow-band CE-Chirp ASSR(NB CE-Chirp ASSR)and modulated acoustic ASSR in the assessment of hearing threshold in children with hearing impairment.METHODS Forty-eight children with sensorineural hearing loss were tested by pure tone audiometry(PTA),NB CE-Chirp ASSR and modulated acoustic ASSR.According to the results of pure tone audiometry,they were divided into mild to moderate group(48 ears)and severe to profound group(48 ears).The difference and correlation between pure tone hearing threshold and ASSR response threshold of different stimuli were compared between 500-4 000 Hz.RESULTS The absolute differences between the NB CE-Chirp ASSR response threshold and the PTA threshold in 48 children were all smaller than the differences between the modulated acoustic ASSR response threshold and the PTA threshold,and the differences were statistically significant(P<0.001).Under the same stimulus sound,the absolute difference between ASSR response threshold and pure tone hearing threshold in the mild to moderate group was higher than that in the severe to very severe group.The correlation coefficients between NB CE-Chirp ASSR threshold and pure tone hearing threshold are higher than those between modulated sound ASSR threshold and pure tone hearing threshold at 500-4 000 Hz.The test time of NB CE-Chirp ASSR[(20.92±9.33)min]was significantly shorter than that of modulated acoustic ASSR[(33.68±10.97)min](P=0.004).CONCLUSION NB CE-Chirp ASSR can more accurately assess the hearing threshold of children with different degrees of hearing loss than modulated acoustic ASSR.

Objective:To explore the effects and safety of Qigong Pills in IVF-ET outcome of PCOS infertility patients with phlegm-dampness type.Methods:A randomized controlled trial study was carried out. In the Reproductive and Genetic Medicine Center of Dalian Women and Children Medical Center (Group) from January 2021 to December 2023, 60 patients with sputum and damp-induced PCOS infertility assisted by in-vitro fertilization and embryo transfer (IVF-ET) were enrolled and randomly divided into 2 groups by block randomization method, with 30 cases in each group. Patients in both groups took ethinylestradiol cyproterone tablets orally on the 2nd to 5th day of the 1st menstrual cycle before IVF-ET cycle, and received down-regulation treatment on the 18th to 20th day of menstruation. After confirming that the down-regulation standard was reached, Qigong Pills was added to the treatment group, and placebo was taken orally until the trigger day. Two groups of patients underwent transvaginal ultrasound-guided ovarian aspiration after injection of chorionic gonadotropin (hCG) for 24-36 h. The total amount of Gn, the days of Gn, the endometrial thickness of HCG, the number of eggs obtained, the rate of diprokaryotic (2PN) fertilization, the number of transferable embryos, the number of high-quality embryos, the rate of high-quality embryos, the incidence of OHSS and the clinical pregnancy rate were compared between the two groups.Results:Among the 60 patients, 28 cases in the final treatment group and 27 cases in the control group were included in the outcome index evaluation. During controlled hyperstimulation (COH), the total Gn [2 025 (1 575, 2 325) U vs. 2 700 (2 025, 3 150) U, Z=-3.67] and the number of Gn days of the treatment group [10 (8,11) d vs. 11 (9,13) d, Z=-2.31] were lower than those in control group ( P<0.001 or P<0.05). There was no statistical significance in endometrial thickness between 2 groups on HCG day ( P>0.05); the number of high-quality embryos [3 (3, 4) vs. 2 (2, 3), Z=0.11] and the rate of high-quality embryos [46.28% (87/188) vs. 35.19% (57/162), Z=4.42] in the treatment group were higher than those in the control group ( P<0.05). There was no statistical significance in the number of eggs obtained, the fertilization rate of 2PN and the number of transferable embryos between the two groups ( P>0.05). The incidence of OHSS was 3.6% (1/28) in the treatment group and 11.1% (3/27) in the control group, without statistical significance ( P=0.352). The clinical pregnancy rate was 53.6% (15/28) in the treatment group and 37.0% (10/27) in the control group, without statistical significance ( P=0.218). There was no significant difference in the safety indexes of liver and kidney function between 2 groups ( P>0.05). Conclusion:Qigong Pills combined with IVF-ET can effectively reduce the total amount of Gn and the number of days of treatment in PCOS infertility patients with phlegm-dampness type, increase the number and rate of high-quality embryos, and improve the outcome of IVF-ET, and it is safe and effective.

POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

Objective:To identify proteins associated with the risk of gastric cancer (GC) and build a protein risk score for risk prediction of GC based on proteomic analysis.Methods:Gastric mucosal proteomics data were used to construct Dataset One, comprising 94 GC cases and 230 individuals with different stages of gastric mucosal lesions. The GC cases were recruited from the National Upper Gastrointestinal Cancer Early Detection (UGCED) Program in Linqu, Shandong Province, as well as clinical patients from the Fifth Medical Center, General Hospital of PLA, and Peking University Cancer Hospital. Non-cancer individuals were enrolled from the National UGCED Program in Linqu and community screening programs at the Dongfang Hospital. All participants were pathologically confirmed. Multivariate logistic regression analysis was employed to identify gastric mucosal proteins significantly associated with GC risk. Subsequently, plasma proteomics data from the UK Biobank Pharma Proteomics Project (UKB-PPP) were used to construct Dataset Two, including 40 baseline GC cases and 47 933 non-cancer individuals, and Dataset Three, comprising 138 incident GC cases and 47 933 non-cancer individuals during a prospective follow-up period. In Dataset Two, multivariate logistic regression analysis was conducted to assess associations between plasma protein levels and baseline GC risk. In Dataset Three, multivariate Cox regression analysis was used to examine associations with the risk of incident GC. A poly-protein risk score (PRS) was developed using a weighted summation method based on protein effect sizes from Dataset Two. Its associations with GC risk and the progression of gastric mucosal lesions were evaluated using linear regression trend tests.Results:A total of 324, 47 973 and 48 071 participants were included in Datasets One, Two, and Three, respectively. Across the three datasets, the proportions of males and individuals aged>60 years were higher in the GC group than in the non-GC group (all P values<0.05). The follow-up period in Dataset Three had a M ( P 25, P 75) of 14.47 (13.7, 15.2) years, with a median of 7.4 (4.6, 11.3) years for those who progressed to GC. Based on Dataset One, 2 524 tissue-differential proteins associated with GC risk were identified through multivariate logistic regression analysis adjusted for age and sex. Among these, seven proteins were consistently associated with GC risk across tissue and plasma levels in Datasets Two and Three, with consistent directions of association. Five proteins (MRC1, APOL1, BST2, PON2, and GGH) were positively associated with GC risk, while two (GSN and CLEC3B) were negatively associated. Analysis of the PRS based on these seven proteins showed that for each standard deviation increase in the tissue-derived PRS, the risk of GC increased by 6.26 times (95% CI: 4.02-9.75). In Dataset Two, each standard deviation increase in the plasma-derived PRS was associated with a 2.13-fold increase in GC risk (95% CI: 1.68-2.69). In the prospective cohort of Dataset Three, individuals in the high PRS group had a 2.27-fold higher risk of GC compared to the low PRS group (95% CI: 1.50-3.45). Moreover, each standard deviation increase in the plasma PRS was associated with a 57% higher risk of GC ( HR=1.57, 95% CI: 1.34-1.84). Additionally, the tissue-derived PRS showed an increasing trend with the progression of gastric mucosal lesions. Conclusion:The tissue and plasma proteomics identified seven individual proteins that may indicate the risk of developing gastric cancer, showing the potential as biomarkers for aiding in the screening of gastric cancer.

Objective To investigate the distribution of serum specific IgG antibodies against food in children with autism spectrum disorders(ASD),and provide experimental evidence for improving gastrointestinal symptoms of ASD children.Methods A retrospec-tive study was conducted on 411 children with ASD visited the Department of Psychology and Behavior of Hebei Children's Hospital from January 2021 to December 2022.Additionally,631 healthy children who underwent physical examination during the same period were collected as the healthy control group.Their venous blood samples were collected,and ELISA was used to detect the levels of 14 kinds of serum specific IgG antibodies against food.The distribution characteristics of food intolerance in children with different genders and ages were investigated.Results The total positive rate of specific IgG antibodies against food in children with ASD reached 91.84%(405/441).The top 3 positive rates of specific IgG antibodies were against egg(71.89%),milk(56.70%),and wheat(56.02%),respectively,which were significantly higher than those in the healthy control group(χ2=42.81,27.48,and 26.88,re-spectively,P＜0.05).The comparative results of gender composition showed that the positive rate of specific IgG antibody against rice in female ASD children(15.96%)was significantly higher than that in male ASD children(4.90%,χ2=11.84,P＜0.05).The posi-tive rates of specific IgG antibodies against egg and wheat in male and female ASD children were significantly higher than those in the healthy control group(χ2=19.44 and 4.42 for males,χ2=4.66 and 10.93 for females,P＜0.05).The positive rate of specific IgG anti-body against milk in male ASD children was significantly higher than that in the healthy control group(χ2=12.62,P＜0.05),while those against soybean and rice in female ASD children were also significantly higher than that in the healthy control group(χ2=7.00 and 5.42,P＜0.05).There were significant differences in the positive rates of food intolerance to milk and soybean in ASD children with different ages(χ2=13.74 and 9.70,P＜0.05)and they decreased with age.The positive rates of specific IgG antibody against wheat in ASD children aged 2-3 and 4-6 years were significantly higher than those in the healthy control group(χ2=5.78 and 4.55,P＜0.05).The positive rate of specific IgG antibody against milk in ASD children aged 4-6 years was significantly higher than that in the healthy control group(χ2=7.57,P＜0.05).Conclusion The highest positive rate of specific IgG antibodies against food in ASD chil-dren is against egg,which is not related to the patient's gender.Next are milk and wheat.The gastrointestinal issues and related food intolerance should be taken into account in the management of patients with ASD.

Objective:This meta-analysis compares the postoperative outcomes of the double-flap technique (DFT) versus esophagogastrostomy (EG), jejunal interposition (JI), double-tract reconstruction (DTR), and gastric tube anastomosis (GTA) following proximal gastrectomy for gastric cancer.Methods:Prospective and retrospective studies published from database inception until June 2025 were retrieved from PubMed, Embase, Web of Science, Scopus, CNKI, and Wanfang databases. Studies reporting at least one predefined outcome with extractable data were included. Outcomes of interest consisted of incidence of gastroesophageal reflux, overall postoperative complications, anastomotic leakage, anastomotic stenosis, and digestive reconstruction time. Two investigators independently performed literature screening, data extraction, and quality assessment. Randomized controlled trials (RCTs) were evaluated with the Cochrane ROB 2.0 tool, retrospective cohort studies with the Newcastle-Ottawa Scale (NOS), and single-arm studies with the JBI critical appraisal tool. Dichotomous outcomes were pooled using risk ratios (RRs), and continuous variables were summarized with standardized mean differences (SMDs), using fixed- or random-effects models based on I2 statistics. Publication bias was assessed via funnel plots and Egger's test.Results:A total of 55 studies published between 2007 and 2025 were included, comprising 5 RCTs and 50 retrospective studies. Among 4,380 patients, 732 underwent EG, 454 GTA, 1,480 DTR, 468 JI, and 1,246 DFT. Quality assessment indicated that all except six retrospective cohort studies (rated as moderate quality) were of high quality or had low risk of bias. Among the five reconstruction methods, DFT showed the lowest incidence of gastroesophageal reflux (6.6%, 82/1,246) and overall postoperative complications (11.6%, 144/1,246). JI had the lowest rate of anastomotic leakage (1.3%, 6/468), followed by DFT (1.4%, 18/1,246), and DTR had the lowest rate of anastomotic stenosis (2.4%, 36/1,480), followed by DFT (7.5%, 94/1,246). DFT required the longest operative time for reconstruction ([141.2 ± 597.6] minutes), and DTR required the shortest ([50.1 ± 39.0] minutes). Compared to EG, DFT was associated with a significantly lower risk of gastroesophageal reflux (RR=0.13 ,95%CI: 0.03-0.55, P = 0.01), and no significant differences were observed in overall complications (RR=0.98, 95%CI: 0.55-1.74, P = 0.93), anastomotic leakage (RR = 0.81, 95%CI: 0.04-18.43, P = 0.90), or anastomotic stenosis (RR = 0.75, 95%CI: 0.09-6.39, P = 0.79). Compared to JI, DFT showed no significant differences in gastroesophageal reflux (RR = 0.36, 95%CI: 0.10-1.25, P=0.11), overall complications (RR=2.06, 95%CI: 0.30-14.11, P=0.46), anastomotic leakage (RR=2.05, 95%CI: 0.26-16.18, P=0.49), or anastomotic stenosis (RR=0.83, 95%CI: 0.10-7.17, P=0.87). Similarly, compared to DTR, DFT had a lower risk of overall complications (RR=0.70, 95%CI: 0.50-0.98, P=0.04) but a longer reconstruction time (SMD: 2.55, 95%CI: 0.31-4.79, P=0.03). No significant differences were found in gastroesophageal reflux (RR = 0.68, 95%CI: 0.35-1.30, P=0.24), anastomotic leakage (RR=0.59, 95%CI: 0.16-2.17, P=0.43), or anastomotic stenosis (RR=2.44 , 95%CI: 0.44-13.64, P=0.31). Compared to GTA, DFT was associated with a significantly lower risk of gastroesophageal reflux (RR = 0.53, 95%CI: 0.33-0.88, P=0.01), but again there were no significant differences in overall complications (RR = 0.69, 95%CI: 0.41-1.16, P=0.16), anastomotic leakage (RR = 0.25, 95%CI: 0.03-2.14, P=0.21), or anastomotic stenosis (RR=0.65, 95%CI: 0.24-1.76, P=0.40). No significant publication bias was detected in the analysis (Egger's test P>0.05). Conclusions:Among the five common anastomotic methods after proximal gastrectomy, DFT demonstrates superior anti-reflux efficacy, outperforming EG and GTA in particular in preventing gastroesophageal reflux. DFT also exhibits a lower overall complication risk compared with DTR but maintains anastomotic safety comparable with that of the other techniques.

Cardiovascular nursing research focuses on solving practical nursing problems, and nursing practice is continuously improved based on nursing research. This article provides an overview of the development of cardiovascular nursing research, summarizes and generalizes the current research status and future research hotspots in cardiovascular nursing according to the Fuwai Subject Headings, aiming to provide references for nursing staff.

With the advent of the genomic era, genomics has gradually become a part of nursing. The use of genomic data can explore the mechanisms of disease occurrence and progression, accurately identify intervention targets and regulatory pathways of diseases, provide precise and personalized nursing services for patients, and improve their quality of life. This paper reviews the current application status of genomics in nursing, deeply analyzes the development process of genomics in genetic risk assessment, symptom precision nursing, precision nursing decision-making, and nursing education, and proposes corresponding development strategies. Through a comprehensive and in-depth exploration of the combination of genomics and nursing, the aim is to provide strong theoretical guidance for the future development of genomics nursing in China.