Dimethyl fumarate treatment for unruptured intracranial aneurysms: a study protocol for a double-blind randomised controlled trial.

INTRODUCTION: Intracranial aneurysm (IA) is a common cerebrovascular disease. Considering the risks and benefits of surgery, a significant proportion of patients with unruptured IA (UIA) choose conservative observation. Previous studies suggest that inflammation of aneurysm wall is a high-risk factor of rupture. Dimethyl fumarate (DMF) acts as an anti-inflammatory agent by activating nuclear factor erythroid 2-related factor 2 (Nrf2) and other pathways. Animal experiments found DMF reduces the formation and rupture of IAs. In this study, DMF will be evaluated for its ability to reduce inflammation of the aneurysm wall in high-resolution vessel wall imaging. METHODS AND ANALYSIS: This is a multi-centre, randomised, controlled, double-blind clinical trial. Three hospitals will enrol a total of 60 patients who have UIA with enhanced wall. Participants will be assigned randomly in a 1:1 proportion, taking either 240 mg DMF or placebo orally every day for 6 months. As the main result, aneurysm wall enhancement will be measured by the signal intensity after 6 months of DMF treatment. Secondary endpoints include morphological changes of aneurysms and factors associated with inflammation. This study will provide prospective data on the reduction of UIA wall inflammation by DMF. ETHICS AND DISSEMINATION: This study has been approved by Medical Ethics Committee of the Beijing Tiantan Hospital, Capital Medical University (approval no: KY2022-064-02). We plan to disseminate our research findings through peer-reviewed journal publication and relevant academic conferences. TRIAL REGISTRATION NUMBER: NCT05959759.

Global trend in research of intracranial aneurysm management with artificial intelligence technology: a bibliometric analysis.

Background: The use of artificial intelligence (AI) technology has been growing in the management of intracranial aneurysms (IAs). This study aims to conduct a bibliometric analysis of researches on intracranial aneurysm management with artificial intelligence technology (IAMWAIT) to gain insights into global research trends and potential future directions. Methods: A comprehensive search of articles and reviews related to IAMWAIT, published from January 1, 1900 to July 20, 2023, was conducted using the Web of Science Core Collection (WoWCC).Visualizations of the bibliometric analysis were generated utilizing WPS Office, Scimago Graphica, VOSviewer, CiteSpace, and R. Results: A total of 277 papers were included in the study. China emerged as the most prolific country in terms of publications, institutions, cooperating countries, and prolific authors. The United States garnered the highest number of total citations, institutions with the highest citations/H index, cooperating countries (n=9), and 3 of the top 10 cited papers. Both the total number of papers and the citation count exhibited a positive and significant correlation with the gross domestic product (GDP) of countries. The journal with the highest publication frequency was Frontiers in Neurology, while Stroke recorded the highest number of citations, H-index, and impact factor (IF). Areas of primary interest in IAMWAIT, leveraging AI technology, included rupture risk assessment/prediction, computer-assisted diagnosis, outcome prediction, hemodynamics, and laboratory research of IAs. Conclusions: IAMWAIT is an active area of research that has undergone rapid development in recent years. Future endeavors should focus on broader application of AI algorithms in various sub-fields of IAMWAIT to better suit the real world.

Treatment of Intracranial Vertebral Artery Dissecting Aneurysms Using Pipeline Embolization Devices : A Multicenter Cohort Study.

PURPOSE: Intracranial vertebral artery dissecting aneurysm (IVADA) is a rare type of aneurysm with high morbidity and mortality. Recently, the application of pipeline embolization devices (PEDs) has been extended to IVADAs. Here, we aim to investigate the safety and effectiveness of PEDs for IVADAs. METHOD: We retrospectively reviewed the PLUS database to identify patients who had IVADAs and were treated with PEDs from 2014 to 2019 at 14 centers across China. Data including patient and aneurysm characteristics, procedure details, angiographic and clinical results, relationship with the ipsilateral posterior inferior cerebellar artery (PICA), and patency of the PICA following PED coverage were analyzed. RESULTS: In this study 52 consecutive patients with 52 IVADAs were included. The mean age was 52.33 years and 82.7% were male. With a median follow-up of 10.5 months, the complete occlusion rate was 93.8% (45/48) and no recurrence or in-stent stenosis was detected. The total postoperative complication rate and mortality were 11.5% and 1.9%, respectively. Complications occurred in 9.6% (5/52) of patients within 30 days after the operation, including ischemic stroke in 3 and hemorrhagic stroke in 2. Another patient suffered an ischemic stroke at follow-up, 78.8% (41/52) PICAs were covered by PEDs, 1 case (2.4%) had a functional disability due to PICA occlusion, while 39.0% (16/41) had reduced flow during follow-up but hardly caused any obvious neurological deficits. Patients with IVADA involving PICA had a trend towards more complications (66.7% vs. 51.1%; P = 1). CONCLUSION: Treating IVADAs with PEDs may be a safe and effective option, with favorable clinical and angiographic outcomes; however, complications associated with this treatment should not be ignored. REGISTRATION: http://www. CLINICALTRIALS: gov . Unique identifier: NCT03831672.

Development and validation of a deep learning model for prediction of intracranial aneurysm rupture risk based on multi-omics factor.

OBJECTIVE: The clinical ability of radiomics to predict intracranial aneurysm rupture risk remains unexplored. This study aims to investigate the potential uses of radiomics and explore whether deep learning (DL) algorithms outperform traditional statistical methods in predicting aneurysm rupture risk. METHODS: This retrospective study included 1740 patients with 1809 intracranial aneurysms confirmed by digital subtraction angiography at two hospitals in China from January 2014 to December 2018. We randomly divided the dataset (hospital 1) into training (80%) and internal validation (20%). External validation was performed using independent data collected from hospital 2. The prediction models were developed based on clinical, aneurysm morphological, and radiomics parameters by logistic regression (LR). Additionally, the DL model for predicting aneurysm rupture risk using integration parameters was developed and compared with other models. RESULTS: The AUCs of LR models A (clinical), B (morphological), and C (radiomics) were 0.678, 0.708, and 0.738, respectively (all p < 0.05). The AUCs of the combined feature models D (clinical and morphological), E (clinical and radiomics), and F (clinical, morphological, and radiomics) were 0.771, 0.839, and 0.849, respectively. The DL model (AUC = 0.929) outperformed the machine learning (ML) (AUC = 0.878) and the LR models (AUC = 0.849). Also, the DL model has shown good performance in the external validation datasets (AUC: 0.876 vs 0.842 vs 0.823, respectively). CONCLUSION: Radiomics signatures play an important role in predicting aneurysm rupture risk. DL methods outperformed conventional statistical methods in prediction models for the rupture risk of unruptured intracranial aneurysms, integrating clinical, aneurysm morphological, and radiomics parameters. KEY POINTS: • Radiomics parameters are associated with the rupture risk of intracranial aneurysms. • The prediction model based on integrating parameters in the deep learning model was significantly better than a conventional model. • The radiomics signature proposed in this study could guide clinicians in selecting appropriate patients for preventive treatment.

Treatment of fusiform aneurysms with a pipeline embolization device: a multicenter cohort study.

BACKGROUND: Intracranial fusiform aneurysms are less common than saccular aneurysms, but are associated with higher mortality and morbidity. We conducted this study to determine the safety and efficacy of the pipeline embolization device (PED) to treat intracranial fusiform aneurysms. METHODS: This was a multicenter, retrospective, and observational study. Data for this study came from the PLUS study conducted from 2014 to 2019 across 14 centers in China. Univariate and multivariable logistic regression analyses were performed to evaluate predictors of the occlusion rate and complication. RESULTS: A total of 1171 consecutive patients with 1322 intracranial aneurysms participated in this study. Among the participants, 104 patients with 109 fusiform aneurysms were eligible for this analysis (mean age 49 years, 36.5% women, aneurysm mean size 14.7 mm, 55% in the posterior circulation, and 6% in the basilar artery). Mean follow-up time was 9.0 months (range 3-36 months). The last DSA angiographic follow-up was available for 85 patients, and 58 aneurysms (68.2%) were completely occluded. The overall complication rate and mortality were 17.3% and 2.8%, respectively. Multivariate analysis demonstrated that age (OR=1.007, p=0.037) and cerebral atherosclerosis (OR=1.441, p=0.002) were associated with incomplete occlusion of fusiform aneurysms after PED treatment. CONCLUSION: PEDs may be an effective treatment for intracranial fusiform aneurysms, with a favorable occlusion rate. However, because these treatments have a relatively high rate of complications, PED treatment for fusiform aneurysms should be carefully and strictly controlled. Our analysis showed that PEDs with adjunctive coiling did not significantly improve the occlusion rate of fusiform aneurysms.

In-Stent Stenosis After Pipeline Embolization Device in Intracranial Aneurysms: Incidence, Predictors, and Clinical Outcomes.

BACKGROUND: In-stent stenosis (ISS) is a delayed complication that can occur after pipeline embolization device use when treating intracranial aneurysms (IAs). OBJECTIVE: To assess the incidence, predictors, and outcomes of ISS. METHODS: This was a retrospective, multicenter, observational study. All patient data were collected from a PLUS registry study. We collected data from patients with IA who completed digital subtraction angiography at follow-up and divided patients into "non-ISS," "mild ISS," or "severe ISS" groups. Multivariate logistic regression analysis was conducted to determine predictors of ISS. RESULTS: A total of 1171 consecutive patients with 1322 IAs participated in this study. Angiographic follow-up was available for 662 patients with 728 IAs, and the mean follow-up time was 9 months. ISS was detected in 73 cases (10.03%), including 61 mild ISS cases and 12 severe ISS cases. Univariate and multivariable analysis demonstrated that current smoking history (mild ISS: OR 2.15, 95% CI 1.122-4.118, P = .021; severe ISS: OR 5.858, 95% CI 1.186-28.93, P = .030) and cerebral atherosclerosis (mild ISS: OR 5.694, 95% CI 3.193-10.15, P = .001; severe ISS: OR 6.103, 95% CI 1.384-26.91, P = .017) were independent predictors of ISS. Compared with the other groups, the severe ISS group had higher rate of ischemic stroke (33.3%). CONCLUSION: ISS occurs in approximately 10.03% of cases at a mean follow-up of 9 months. Statistically, current smoking history and cerebral atherosclerosis are the main predictors of ISS. Severe ISS may be associated with higher risk of neurological ischemic events in patients with IA after pipeline embolization device implantation.

Attitudes toward posthumous assisted reproduction in China: a multi-dimensional survey.

BACKGROUND: Professional legislation and ethics guidelines for posthumous assisted reproduction (PAR) are lacking in China. This study aims to measure the attitudes of the general public, IVF couples, and assisted reproductive technology (ART) practitioners toward PAR in China. METHODS: A multi-dimensional survey was designed, and electronic questionnaires were used. General demographic data, reproductive viewpoints, attitudes toward PAR, interactive ability to predict the partner's attitude toward PAR, and the legal attributes and rights to the disposal of posthumous embryos were evaluated. RESULTS: The study found that the traditional Chinese viewpoints of fertility had changed. The approval rates for PAR were 79.10%, 55.32%, and 58.89%, in the general public, IVF couples, and ART practitioners, respectively. Most participants agreed that the psychological well-being of offspring should be previously considered before making a PAR decision (81.84%, 73.61%, and 76.98%, respectively). Multivariable logistic regression analysis showed that age, marital status, and gender were common influencing factors, while occupation, religion, and pregnancy history showed no influence on support for PAR. Males and females showed similar predictive abilities for their partners' attitudes toward PAR (57.87% for males, 61.12% for females). Intracouple agreement analysis showed that the consistent rate of consistency in attitudes toward PAR was 65.28%. CONCLUSION: The findings suggested that the approval rate of PAR was relatively high in China. Legislation and ethics guidelines for PAR may be considered in China. The psychological well-being of offspring should be considered before the implementation of PAR. Due to the very large regional and demographic differences in China, investigation of a larger samples of participants is necessary.

This study is based on the dilemma of how to deal with the remaining frozen embryos when a family structure changes (such as the accidental death of one or both partners). In this research, we systematically investigated the basic attitudes of different groups toward PAR, the consistency and prediction accuracy of attitudes between couples and their ability to predict their partners' attitudes, and the balance between offspring well-being and reproduction through a multi-dimensional cross-sectional survey in China. Our study illustrated that the approval rates of PAR were relatively high among the public, IVF couples and ART practitioners. Couples' attitude prediction accuracy and the intercouple concordance were moderate. The psychological well-being of offspring should be considered before the implementation of PAR. Moreover, an appropriate legal policy or specialized guidance for PAR may be considered and published in China. This research provides some advice and evidence for medical professionals and policymakers regarding practice and policymaking related to PAR. We also believe that this manuscript is valuable and helpful for all the researchers who are interested in the posthumous reproduction, not only in China.

Atorvastatin for unruptured intracranial vertebrobasilar dissecting aneurysm (ATREAT-VBD): protocol for a randomised, double-blind, blank-controlled trial.

INTRODUCTION: Vertebrobasilar dissecting aneurysms (VBDAs) are associated with serious complications and a poor prognosis. It is believed that inflammation of the aneurysm wall may be the main cause of rupture or deterioration. Atorvastatin has been shown to inhibit inflammation and may be a suitable drug candidate. Here, we report a clinical research study protocol to investigate whether atorvastatin inhibits inflammation of the aneurysm wall, as measured by signal index enhancement. METHODS AND ANALYSIS: We have designed a single-centre, randomised, double-blind, blank-controlled clinical trial. 40 patients with non-ruptured VBDAs with enhancement aneurysm walls will be enrolled in Beijing Tiantan Hospital. Eligible patients will be randomly divided into two treatment groups, at a ratio of 1:1, to receive atorvastatin 20 mg orally for 6 months or no treatment. The primary assessment outcome will be the change in aneurysm wall enhancement, as measured by the signal index during the 6-month treatment period. The secondary assessment outcomes will be the aneurysm morphology (intramural haematoma, dissection valve and false lumen) and changes in the concentrations of inflammatory factors, including C reactive protein, tumour necrosis factor-α, interleukin (IL)-1ß and IL-6. ETHICS AND DISSEMINATION: The protocol has been approved by the medical ethics committee of the Beijing Tiantan Hospital at which the work will be conducted (Approval No. KY 2019-024-02). Written informed consent will be obtained from all participants. Findings from the study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04943783.

Elevated RIF1 participates in the epigenetic abnormalities of zygotes by regulating histone modifications on MuERV-L in obese mice.

BACKGROUND: Maternal obesity impairs embryonic developmental potential and significantly increases the risks of metabolic disorders in offspring. However, the epigenetic transmission mechanism of maternal metabolic abnormalities is still poorly understood. METHODS: We established an obesity model in female mice by high-fat diet (HFD) feeding. The effects of the HFD on the developmental potential of oocytes and embryos, the metabolic phenotype, and epigenetic modifications were investigated. The efficacy of metformin administration was assessed. Finally, the regulatory pathway of epigenetic remodeling during zygotic genome activation (ZGA) was explored. RESULTS: Maternal HFD consumption significantly impaired glucose tolerance and increased the risk of metabolic disorders in F0 and F1 mice. Maternal HFD consumption also decreased embryonic developmental potential, increased reactive oxygen species (ROS) and γH2AX levels, and reduced the mitochondrial membrane potential (MMP) within oocytes, causing high levels of oxidative stress damage and DNA damage. Starting with this clue, we observed significantly increased RIF1 levels and shortened telomeres in obese mice. Moreover, significant abnormal DNA methylation and histone modification remodeling were observed during ZGA in obese mice, which may be coregulated by RIF1 and the ZGA marker gene MuERV-L. Metformin treatment reduced RIF1 levels, and partially improved ZGA activation status by rescuing epigenetic modification remodeling in oocytes and preimplantation embryos of obese mice. RIF1 knockdown experiments employing Trim-Away methods showed that RIF1 degradation altered the H3K4me3 and H3K9me3 enrichment and then triggered the MuERV-L transcriptional activation. Moreover, ChIP-seq data analysis of RIF1 knockouts also showed that RIF1 mediates the transcriptional regulation of MuERV-L by changing the enrichment of H3K4me3 and H3K9me3 rather than by altered DNA methylation. CONCLUSION: Elevated RIF1 in oocytes caused by maternal obesity may mediate abnormal embryonic epigenetic remodeling and increase metabolic risk in offspring by regulating histone modifications on MuERV-L, which can be partially rescued by metformin treatment.

Human umbilical cord mesenchymal stem cells contribute to the reconstruction of bladder function after acute spinal cord injury via p38 mitogen-activated protein kinase/nuclear factor-kappa B pathway.

The association between spinal cord injury (SCI) and bladder symptoms has been intensively described. Human umbilical cord mesenchymal stem cell (hUC-MSC) treatment is beneficial to the recovery of bladder function after SCI, but its mechanism is unclear. We established an SCI model, and prepared hUC-MSCs in advance, followed by verification using flow cytometry. The Basso, Beattie and Bresnahan (BBB) score and urodynamic index were employed to evaluate motor function and bladder functions, respectively. Hematoxylin-eosin staining, luxol fast blue staining, and Masson's trichrome staining were utilized to assess pathological changes. Real-time quantitative PCR and Western blot were used to determine the mRNA and protein expressions in bladder tissues. The immunophenotypes of the HUC-MSCs were CD90+ and CD105+, but CD34-, CD45- and HLA-DR-. Rats appeared severe motor dysfunction after SCI, but the BBB score was increased in hUC-MSCs after the second week. Pathologically, the improvement of the lesion area on the dorsal spinal cord, augmented anterior gray horn neuron cells of the spinal cord and lessened bladder tissue remodeling (fibrosis, collagen deposition) as well as modulated inflammation could be observed. Besides, SCI increased bladder weight, bladder capacity, urine volume and residual urine volume, and decreased urination efficiency. HUC-MSCs ameliorated SCI-induced pathological changes and bladder functions, the expressions of Collagen I, Collagen III, fibroblast growth factor 2 (FGF2), phospho-p38, transient receptor potential vanilloid 1, Toll-like receptor 4 and phospho-nuclear factor-kappa B (p-NF-κB). To sum up, HUC-MSCs contribute to the reconstruction of bladder function after SCI by repressing p38 MAPK/NF-κB pathway.

The regulation of the follicular synchronization and sensitivity of rats with PCOS by AMH during prolonged pituitary downregulation.

The modified prolonged gonadotropin-releasing hormone agonist (GnRH-a) protocol lessens the ovarian hyperstimulation syndrome (OHSS) effect and improves the clinical pregnancy rate of women with polycystic ovary syndrome (PCOS) compared with the standard long GnRH-a protocol. However, the molecular basis of this process needs to be elucidated. Sprague Dawley (SD) female rats with letrozole-induced PCOS were divided into GnRH-a and blank groups. Rats in the GnRH-a group were given triptorelin for 11 days, whereas those in blank group were given an equal volume of 0.9% NaCl. Meanwhile, the changes in estrus cycle, hormonal profile, ovary index, ovarian histopathology and body weight were measured. The expressions of anti-mullerian hormone (AMH), type II receptor of AMH (AMHRII), and FSH receptor (FSHR) were taken as the indicators of follicular sensitivity. Changes of follicular counting and differences in antral follicle diameter at each stage were evaluated. The number of follicles from primordial to antral stages increased during downregulation and the differences in antral follicle diameter were reduced in the GnRH-a group, whereas no significant difference was found in the blank group. The results of Western blotting and ELISA indicated that the level of AMH in ovarian total protein and serum had a similar dynamic change in the GnRH-a group. The results of immunohistochemistry showed that follicular AMH, AMHRII, and FSHR significantly decreased in the GnRH-a group. Prolonged GnRH-a protocol can improve synchronization and sensitivity of follicular development by balancing the expressions of AMH, AMHRII, and FSHR among follicles at all levels, thereby achieving better therapeutic effect.

Acute abrin poisoning treated with continuous renal replacement therapy and hemoperfusion successfully: A case report.

RATIONALE: Abrin is a highly toxic protein obtained from the seeds of Abrus precatorius, but poisoning due to ingestion of A precatorius is extremely rare in China. PATIENT CONCERNS: A 16-year-old girl, perfectly healthy before, was admitted to the department of gastroenterology owing to intentional ingestion of 10 crushed A precatorius seeds, with multiple episodes of somnolent and anxious mental status, vomiting, abdominal pain, diarrhea, hematochezia, and hematuria. DIAGNOSIS: Acute abrin poisoning. INTERVENTIONS: We immediately took effective measures including gastric lavage, purgation, gastric acid suppression by proton pump inhibitor (PPI), liver protection, hemostasis, blood volume and electrolytes resuscitation, continuous renal replacement therapy (CRRT), and hemoperfusion (HP). OUTCOMES: Her unwell mental status was improved to the point at which she became conscious and relaxed. The symptoms of vomiting, abdominal pain, diarrhea, hematochezia, and hematuria disappeared gradually. The girl eventually made an excellent recovery with no complications at her 3-month follow-up. LESSONS: The combination of CRRT and HP is an efficient measure in the treatment of abrin poisoning for which there is no specific antidote. This is the first reported case of an abrin poisoning patient successfully treated by CRRT plus HP. Our experience will be useful to other physicians in managing patients of acute abrin poisoning in the future.

A home-based, nurse-led health program for postoperative patients with early-stage cervical cancer: A randomized controlled trial.

PURPOSE: To investigate the effect of a home-based, nurse-led health program on quality of life and family function for postoperative patients with early-stage cervical cancer. METHOD: 226 cervical cancer patients, from two hospitals between December 2012 and April 2014, were randomly divided into intervention and control groups. Patients in the intervention group received an individual home-based, nurse-led health program (family-care team provision, physiological rehabilitation, emotion-release management, informal social support system, and follow-up monitoring), in addition to conventional nursing education. Patients in the control group only received conventional nursing education. The Functional Assessment Cancer Therapy-Cervix, Female Sexual Function Index, and the Family Adaptability and Cohesion Scale were used for assessment before and after the intervention. RESULTS: After the intervention, significant improvements were found for the quality of life total scores (t=-7.650, p=0.000), sexual function scores (t=-6.465, p=0.000), cohesion scores (t=-8.417, p=0.001) and adaptability scores (t=-10.735, p=0.000) in the intervention group. Moreover, proportions of family types were also improved (χ2 = 17.77, p=0.000). However, for the control group, no significant differences were found except for a decrease in sexual function scores (t = -4.035, p=0.000). Significant differences in change scores between groups were also found for quality of life (F=41.980, p=0.000), Sexual function (F=37.380, p=0.000), cohesion (F=15.268, p=0.000) and adaptability (F=16.998, p=0.000). CONCLUSION: A home-based, nurse-led health promotion program improves the quality of life, sexual function and family function in postoperative patients with early-stage cervical cancer.

Effects of GnRH agonists on the expression of developmental follicular anti-mullerian hormone in varying follicular stages in cyclic mice in vivo.

Gonadotrophin­releasing hormone (GnRH) agonists (GnRHa) have been widely used to induce a state of downregulation for in vitro fertilization, and its direct effects on the pituitary are well known. However, the effects of GnRHa on the expression of anti­mullerian hormone (AMH) by follicles in varying stages in vivo remain to be fully elucidated. In the present study 84 cyclic mice were randomly divided equally into four GnRHa groups and three cyclic mice were used as a control group. The expression levels of AMH in follicles of varying stages between days 0 and 7 following GnRHa administration were quantified using immunohistochemistry. The expression of AMH in follicles at various stages revealed dynamic changes during the process of downregulation. AMH in primary follicles initially increased and then decreased gradually. In small and large preantral follicles and in granulosa cells (GCs) surrounding the oocyte of small antral follicles, the expression of AMH began to increase on day 1, was attenuated on day 2, and then increased to a peak. The expression levels of AMH in the GCs surrounding the basement membrane, in contrast to the GCs surrounding the oocyte, were significantly lower and did not increase on day 1. In all stages of follicles, the expression of AMH declined gradually between the peak level and last day of downregulation. On day 7, the varying follicular stages all expressed lower levels of AMH than on day 0. This decrease was more prominent in the higher dose groups, compared with the lower dose groups. In conclusion, GnRHa was observed to induce time­dependent changes in the expression of AMH at varying follicular stages, which occurred in a dose­dependent manner.

Phospho-Cdc25 correlates with activating G2/M checkpoint in mouse zygotes fertilized with hydrogen peroxide-treated mouse sperm.

The presence of oxidative stress in sperm cryopreservation induces sperm DNA damage. Our previous study has discovered that γH2AX, the DNA-damaged marker, was activated in the early mouse embryos fertilized with hydrogen peroxide (H2O2)-treated sperm. Furthermore, we found that checkpoint proteins ATM and Chk1 were phosphorylated and activated in the early mouse embryos. On the basis of previous researches, we examined the effects of sperm DNA damage on cell cycle arrest in mouse zygotes fertilized with H2O2-treated sperm. Development of fertilized eggs arrested at the PN disappearance stage. At 19 and 24 hours post-insemination (hpi), the percentage of zygotes at the PN disappearance stage was higher in H2O2-treated group compared to the control group. Immunofluorescence staining revealed Phospho-Cdc25C (Ser216) and Phospho-Cdc25B (Ser323) in or surrounding a single pronucleus, following insemination with H2O2-treated sperm. Our study suggests that fertilization with DNA-damaged sperm results in cell cycle arrest mediated by G2/M checkpoint activation in one of the pronuclei in mouse zygotes fertilized with H2O2-treated sperm; Phospho-Cdc25C and Phospho-Cdc25B correlate with activating G2/M checkpoint in zygotes fertilized with H2O2-treated sperm.