Ischemic stroke is an acute serious cerebrovascular disease with high mortality and disability. Ferroptosis is an important regulated cell death (RCD) in ischemic stroke. 15‐Hydroxyprostaglandin dehydrogenase (15‐PGDH), a degrading enzyme of prostaglandin E2 (PGE2), is shown to regulate RCD such as autophagy and apoptosis. The study aimed to determine whether 15‐PGDH regulates ferroptosis and ischemic stroke, and further the exact mechanism. We demonstrated that overexpression of 15‐PGDH in the brain tissues or primary cultured neurons significantly aggravated cerebral injury and neural ferroptosis in ischemic stroke. While inhibition of 15‐PGDH significantly protected against cerebral injury and neural ferroptosis, which benefits arise from the activation of the PGE2/PGE2 receptor 4 (EP4) axis. While the impact of 15‐PGDH was abolished with glutathione peroxidase 4 (GPX4) deficiency. Then, 15‐PGDH inhibitor was found to promote the activation of cAMP‐response element‐binding protein (CREB) and nuclear factor kappa‐B (NF‐κB) via the PGE2/EP4 axis, subsequently transcriptionally upregulate the expression of GPX4. In summary, our study indicates that inhibition of 15‐PGDH promotes the activation PGE2/EP4 axis, subsequently transcriptionally upregulates the expression of GPX4 via CREB and NF‐κB, and then protects neurons from ferroptosis and alleviates the ischemic stroke. Therefore, 15‐PGDH may be a potential therapeutic target for ischemic stroke.

There are still no unified guidelines of surgical treatment and timing for human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM). The clinical data and follow-up data were collected from HIV-negative CM patients in Xiangya Hospital of Central South University from January 2009 to November 2018, and 42 patients who were treated with surgical intervention were enrolled in the present study. These 42 patients were divided into ventriculoatrial (VA) group, ventriculoperitoneal group, external ventricle drainage (EVD) group, hydrocephalus (HYC) group, non-HYC group, EVD group, and non-EVD group (VA/ ventriculoperitoneal) according to different surgical procedures. Statistical analyses were conducted using SPSS (version 19.0, Chicago, IL). Signs of headache, fever, and loss of consciousness in the VA group were significantly improved compared with the EVD group at 1 week after operation (P < .05). The mortality rate of the VA group was significantly lower than that of the EVD group (P < .05). Moreover, male patients were more prone to have HYC (P < .05). Younger patients tended to develop HYC (P < .05). Cerebrospinal fluid sugar in the non-HYC group was significantly lower compared with the HYC group (P < .05). Time of CM-to-operation in the non-HYC group was markedly shorter compared with the HYC group (P < .01). VA procedure could be one of the first choices for the treatment of uncontrollable intracranial hypertension caused by CM. Severe uncontrollable headache, loss of consciousness, and cerebral hernia were indications of emergency surgery. Repeated headache, hearing impairment, and especially progressive loss of vision were indications of early surgery to avoid permanent damage to nerve functions of HIV-negative CM patients.

Purpose Medulloblastoma (MB), a malignant cerebellar embryonal tumor, is predominantly sporadic, with rare familial cases linked to germline mutations in SUFU, PTCH1, TP53, and APC, primarily driving WNT and SHH molecular subtypes. Familial non-WNT/non-SHH MBs remain poorly understood, with limited genetic insights. Methods This study presents two siblings (11-year-old male, 16-year-old female) with non-WNT/non-SHH MBs. Whole exome sequencing (WES) was performed on tumor samples (MB1-T, MB2-T), peripheral blood (MB2-PB, parents), and analyzed for somatic/germline variants. Screening criteria excluded intronic/synonymous single nucleotide variants (SNVs) and common alleles. Results MB2 harbored somatic chromosome 17q gain (prognostic marker) and two deleterious NF1 mutations (p.G2785V, p.N2788Y), absent in MB1. Germline analysis identified rare variants in KYAT3, SPATA31A6, and CBWD6, with potential roles in metabolic reprogramming (KYAT3) and genomic instability (SPATA31A6). No known MB predisposition syndromes or mutations were detected. Conclusion This first report of familial non-WNT/non-SHH MBs highlights novel somatic (NF1) and germline (KYAT3, SPATA31A6) variants, suggesting unexplored oncogenic mechanisms. The findings underscore the need for further research to elucidate drivers of non-WNT/non-SHH MBs and develop targeted therapies. WES proves critical in uncovering genetic underpinnings of rare familial MBs.

Background: There are still no unified guidelines of surgical treatment and timing for HIV-negative patients with cryptococcal meningitis (CM). Methods: The clinical data and follow-up data were collected from HIV-negative CM patients in Xiangya Hospital of Central South University from January 2009 to November 2018, and 42 patients who were treated with surgical intervention were enrolled in the present study. These 42 patients were divided into ventriculoatrial (VA) group, ventriculoperitoneal (VP) group, external ventricle drainage (EVD) group, hydrocephalus (HYC) group, non-HYC group, EVD group and non-EVD group (VA/VP) according to different surgical procedures. Statistical analyses were conducted using SPSS (version 19.0, Chicago, IL, USA). Results: Signs of headache, fever and loss of consciousness in the VA group were significantly improved compared with the EVD group at 1 week after operation (P<0.05). The mortality rate of the VA group was significantly lower than that of the EVD group (P<0.05). Moreover, male patients were more prone to have HYC (P<0.05). Younger patients tended to develop HYC (P<0.05). Cerebrospinal fluid (CSF) sugar in the non-HYC group was significantly lower compared with the HYC group (P<0.05). Time of CM-to-operation in the non-HYC group was markedly shorter compared with the HYC group (P<0.01). Conclusions: VA procedure could be one of the first choices for the treatment of uncontrollable intracranial hypertension caused by CM. Severe uncontrollable headache, loss of consciousness and cerebral hernia were indications of emergency surgery. Repeated headache, hearing impairment, and especially progressive loss of vision were indications of early surgery to avoid permanent damage to nerve functions of HIV-negative CM patients.