Explore the vast range of titles available.

Intracerebral hemorrhage (ICH) is a severe neurological disease with limited treatment options. Microglia, the primary immune cells of the brain, contribute significantly to secondary injury following ICH, exhibiting heterogeneity in response across different stages of ICH. However, the exact mechanisms regulating this process remain incompletely elucidated. In this study, we utilized single-nucleus RNA sequencing (snRNA-seq) in conjunction with the ICH model of mice to establish a comprehensive single-nucleus transcriptomic atlas for ICH and further elucidate its pathogenesis to identify potential therapeutic targets. We identified five principal brain clusters with cell-type specific gene expression patterns. Focused on microglia and inflammation-associated subgroup, we identified 8 distinct microglia subtypes and the key transcription factors (TFs) involved in the inflammatory response of microglia following ICH, including Stat2 , Stat1 , Irf7 , Nfkb1 , Etv6 , Cebpb , Batf , and Bach1 . Notably, Stat2 and Stat1 were identified as the most central TFs. In vitro experiments revealed that inhibiting Stat2 and Stat1 can attenuate the inflammatory response in microglia after ICH. Overall, our findings enhance the understanding of cell responses in ICH and highlight potential therapeutic targets, specifically suggesting that inhibiting STAT1 and STAT2 could mitigate microglial-mediated inflammation in ICH.

Despite stroke being one of the major and increasing burdens to global health, therapeutic interventions in intracerebral haemorrhage (ICH) continue to be a challenge. Existing treatment methods, such as surgery and conservative treatment have shown limited efficacy in improving the prognosis of ICH. However, more and more studies show that exploring the specific process of immune response after ICH and taking corresponding immunotherapy may have a definite significance to improve the prognosis of cerebral haemorrhage. Therefore, immune interventions are currently under consideration as therapeutic interventions in the ICH. In this review, we aim to clarify unique immunological features of stroke, and consider the evidence for immune interventions. In acute ICH, activation of glial cells and cell death products trigger an inflammatory cascade that damages vessels and the parenchyma within minutes to hours of the haemorrhage. Immune interventions that ameliorate brain inflammation, vascular permeability and tissue oedema should be administered promptly to reduce acute immune destruction and avoid subsequent immunosuppression. A deeper understanding of the immune mechanisms involved in ICH is likely to lead to successful immune interventions.

Zi-Jiang Chen and Yongyong Shi report a genome-wide association study for polycystic ovary syndrome, a common metabolic and endocrine disorder in women. They identified three susceptibility loci associated with this condition. Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P -value by meta-analysis P meta = 7.55 × 10 −21 , odds ratio (OR) 0.71); 2p21 (rs13429458, P meta = 1.73 × 10 −23 , OR 0.67); and 9q33.3 (rs2479106, P meta = 8.12 × 10 −19 , OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended.

Due to the limited capacity of the adult mammalian brain to self-repair and regenerate, neurological diseases, especially neurodegenerative disorders and stroke, characterized by irreversible cellular damage are often considered as refractory diseases. Neural stem cells (NSCs) play a unique role in the treatment of neurological diseases for their abilities to self-renew and form different neural lineage cells, such as neurons and glial cells. With the increasing understanding of neurodevelopment and advances in stem cell technology, NSCs can be obtained from different sources and directed to differentiate into a specific neural lineage cell phenotype purposefully, making it possible to replace specific cells lost in some neurological diseases, which provides new approaches to treat neurodegenerative diseases as well as stroke. In this review, we outline the advances in generating several neuronal lineage subtypes from different sources of NSCs. We further summarize the therapeutic effects and possible therapeutic mechanisms of these fated specific NSCs in neurological disease models, with special emphasis on Parkinson’s disease and ischemic stroke. Finally, from the perspective of clinical translation, we compare the strengths and weaknesses of different sources of NSCs and different methods of directed differentiation, and propose future research directions for directed differentiation of NSCs in regenerative medicine.

The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting.

Background The ovarian reserve is a reservoir for reproductive potential. In clinical practice, early detection and treatment of premature ovarian decline characterized by abnormal ovarian reserve tests is regarded as a critical measure to prevent infertility. However, the relevant data are typically stored in an unstructured format in a hospital’s electronic medical record (EMR) system, and their retrieval requires tedious manual abstraction by domain experts. Computational tools are therefore needed to reduce the workload. Methods We presented RegEMR, an artificial intelligence tool composed of a rule-based natural language processing (NLP) extractor and a knowledge-based disease scoring model, to automatize the screening procedure of premature ovarian decline using Chinese reproductive EMRs. We used regular expressions (REs) as a text mining method and explored whether REs automatically synthesized by the genetic programming-based online platform RegexGenerator +  + could be as effective as manually formulated REs. We also investigated how the representativeness of the learning corpus affected the performance of machine-generated REs. Additionally, we translated the clinical diagnostic criteria into a programmable disease diagnostic model for disease scoring and risk stratification. Four hundred outpatient medical records were collected from a Chinese fertility center. Manual review served as the gold standard, and fivefold cross-validation was used for evaluation. Results The overall F-score of manually built REs was 0.9444 (95% CI 0.9373 to 0.9515), with no significant difference (paired t test p  > 0.05) compared with machine-generated REs that could be affected by training set sizes and annotation portions. The extractor performed effectively in automatically tracing the dynamic changes in hormone levels (F-score 0.9518–0.9884) and ultrasonographic measures (F-score 0.9472–0.9822). Applying the extracted information to the proposed diagnostic model, the program obtained an accuracy of 0.98 and a sensitivity of 0.93 in risk screening. For each specific disease, the automatic diagnosis in 76% of patients was consistent with that of the clinical diagnosis, and the kappa coefficient was 0.63. Conclusion A Chinese NLP system named RegEMR was developed to automatically identify high risk of early ovarian aging and diagnose related diseases from Chinese reproductive EMRs. We hope that this system can aid EMR-based data collection and clinical decision support in fertility centers.

In this study, MnFe 2 O 4 microspheres were synthesized to activate potassium persulfate complex salt (Oxone) for the degradation of 17β-estradiol (17β-E2) in aqueous solutions. The characteristic of MnFe 2 O 4 was detected by XRD, XPS and SEM-EDS. The experimental results indicated that the degradation of 17β-E2 followed pseudo-first-order kinetics. At 25 °C, 17β-E2 concentration of 0.5 mg/L, MnFe 2 O 4 dosage of 100 mg/L, Oxone dosage of 0.5 mmol/L, and initial pH value of 6.5, the decomposition efficiency of 17β-E2 reached 82.9% after 30 min of reaction. Additionally, free radical quenching experiments and electron paramagnetic resonance analysis demonstrated that SO 4 − • and •OH participated in the reaction process of the whole reaction system, with SO 4 − • being the main reactive oxygen species (ROS). The activation mechanism of the MnFe 2 O 4 /Oxone/17β-E2 system is proposed as follows: MnFe 2 O 4 initially reacts with O 2 and H 2 O in solution to generate active Fe 3+ -OH and Mn 2+ -OH species. Subsequently, Fe 3+ -OH and Mn 2+ -OH react with Oxone in a heterogeneous phase activation process, producing highly reactive free radicals. After four cycles of MnFe 2 O 4 material, the removal rate of 17β-E2 decreased by 24.1%.

Although premature ovarian insufficiency (POI), a common cause of female infertility and subfertility, has a well-established hereditary component, the genetic factors currently implicated in POI account for only a limited proportion of cases. Here, using an exome-wide, gene-based case-control analysis in a discovery cohort comprising 1,027 POI cases and 2,733 ethnically matched women controls from China, we found that heterozygous loss-of-function (LoF) variants of MAX dimerization protein (MGA) were significantly enriched in the discovery cohort, accounting for 2.6% of POI cases, while no MGA LoF variants were found in the matched control females. Further exome screening was conducted in 4 additional POI cohorts (2 from China and 2 from the United States) for replication studies, and we identified heterozygous MGA LoF variants in 1.0%, 1.4%, 1.0%, and 1.0% of POI cases, respectively. Overall, a total of 37 distinct heterozygous MGA LoF variants were discovered in 38 POI cases, accounting for approximately 2.0% of the total 1,910 POI cases analyzed in this study. Accordingly, Mga+/- female mice were subfertile, exhibiting shorter reproductive lifespan and decreased follicle number compared with WT, mimicking the observed phenotype in humans. Our findings highlight the essential role of MGA deficiency for impaired female reproductive ability.

This study aims to analyze the global burden and temporal trends of intracerebral hemorrhage from 1990 to 2019 and to project the burden up to 2030, considering variations across regions, sexes, and age groups. Data were sourced from the GBD (Global Burden of Disease) 2019 study. We assessed ASIR (age-standardized incidence rates), ASMR (age-standardized mortality rates) , and ASDR (age-standardized disability adjusted life year rate) using the BAPC (Bayesian age-period-cohort) model. Spearman's Rho correlation was used to examine the relationship between disease burden and the SDI (Socio-Demographic Index). From 1990 to 2019, the global ASIR, ASMR, and ASDR of intracerebral hemorrhage decreased by 1.52%, 1.64%, and 1.64%, respectively, while absolute case numbers increased. Males consistently exhibited higher ASIR, ASMR, and ASDR than females. The projections suggest that by 2030, the incidence and absolute cases of intracerebral hemorrhage will continue to rise, while mortality rates will decline. Despite reductions in age-standardized rates, the global burden of intracerebral hemorrhage continues to increase due to population growth and aging. Effective prevention and treatment strategies, especially in low-SDI regions, are urgently needed.

Background Hepatocellular carcinoma (HCC) poses considerable difficulties regarding the prognosis and the assessment of treatment efficacy. Additionally, while it is recognized that post-translational modification (PTM) plays a crucial role in modulating HCC progression, their specific prognostic implications in HCC have not been thoroughly investigated. Methods 21 types of PTM (acetylation, succinylation, malonylation, crotonylation, β-hydroxybutyrylation, lactylation, palmitoylation, myristoylation, SUMOylation, NEDDylation, ISGylation, ATG8ylation, FAT10ylation, UFMylation, methylation, glycosylation, biotinylation, S-nitrosylation, phosphorylation, ubiquitination, deubiquitination) were generated consensus cluster. Then, WGCNA was utilized to identify module genes. Finally, a machine learning approach was employed to create PTM.score. Results This analysis revealed two distinct subtypes of PTMs, each characterized by unique molecular signatures. By integrating different categories of genes, including prognosis-related DEGs, module genes, and PTM-related genes, 15 hub genes were identified, and a PTM.score was developed. PTM.score was rigorously validated across independent external cohorts (TCGA-LIHC, LIRI-JP, GSE10143, GSE14520, GSE27150, GSE36376, and GSE76427) and an in-house cohort, demonstrating its reliability and potential applicability. In addition, patients categorized with a low PTM.score displayed a TME that was more actively engaged, which corresponded with a poor prognosis. Furthermore, these patients demonstrated a high level of responsiveness to immunotherapy interventions. Furthermore, an examination using scRNA-seq and spatial transcriptomics indicated that patients with low PTM.score exhibited heightened cell proliferation and malignancy. Conclusion This novel PTM-related prognostic signature could effectively assess the prognosis and therapeutic responses of HCC patients, providing new perspectives for individualized treatment for the patient population.