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Posttraumatic cerebral infarction (PTCI) is a common and relatively serious complication of traumatic brain injury (TBI) without a clear etiology. Evaluating risk factors in advance is particularly important to predict and avoid the occurrence of PTCI. We retrospectively analyzed 297 patients with moderate to severe TBI admitted to the Department of Neurosurgery in our hospital from January 2019 to September 2020 and evaluated the effects of various factors such as age, sex, admission Glasgow Coma Scale (GCS), skull base fracture, subarachnoid hemorrhage (SAH), brain herniation, hypotensive shock, and decompressive craniectomy on the incidence of PTCI. We also performed a multivariate logistics regression analysis on the relevant factors identified and evaluated the diagnostic value of each risk factor in advance by receiver operating characteristic (ROC) analyses. Among the patients, 32 (10.77%) suffered PTCI. The incidence rates of PTCI in those with GCS scores of 3-8 and 9-12 were 15.87% (30/189) and 1.85% (2/108), respectively, while the rates were 18.84% (13/69), 15.03% (29/193), 18.57% (13/70), and 20.59% (14/68) in those with skull base fractures, traumatic SAH, brain herniation, and hypotensive shock, respectively, and 14.38% (23/160) in those who underwent decompressive craniectomy. These differences in PTCI incidence were statistically significant. However, the differences in PTCI incidence caused by patient age and sex were not statistically significant. Low GCS score, skull base fractures, traumatic SAH, brain herniation, hypotensive shock, and decompressive craniectomy are risk factors for the occurrence of PTCI, while age and sex are not significantly correlated with the occurrence of PTCI.

Recently, the role of long noncoding RNA (lncRNA) has been identified in human diseases, and we aim to explore the role of lncRNA antidifferentiation noncoding RNA (ANCR) in glioma. Expression of lncRNA ANCR, enhancer of zeste homolog 2 (EZH2), and phosphatase and tensin homolog (PTEN) in glioma tissues and cells was determined by RT-PCR or western blot assay. The correlation between expression of ANCR, EZH2, and PTEN in glioma tissues was analyzed using Pearson test. The apoptosis, transwell invasion, migration, colony formation, and proliferation assays were conducted to evaluate the influences of lncRNA ANCR depletion, EZH2 reduction, or PTEN elevation on the cell biology of glioma cells. The relationships between ANCR and EZH2, and between EZH2 and PTEN were confirmed through RIP, RNA pull-down, and chromatin immunoprecipitation assays. Our results indicated that ANCR and EZH2 were upregulated and PTEN was downregulated in glioma tissues and cell lines. ANCR expression was positively related to EZH2 expression, while PTEN expression was negatively related to ANCR/EZH2 expression. Inhibited ANCR, reduced EZH2, or elevated PTEN could reduce the ability of invasion, migration, and proliferation, and promote apoptosis of glioma cells. PTEN overexpression or EZH2 inhibition reversed the promotive role of ANCR upregulation in glioma cell growth and metastasis. Mechanistically, PTEN was upregulated in ANCR knockdown glioma cells. EZH2 interacted with ANCR in glioma cells. In conclusion, we have found that restrained ANCR could repress invasion, migration, and proliferation, as well as promote apoptosis of glioma cells through interacting with EZH2 and regulating the expression of PTEN, offering an effective therapeutic target for patients with glioma.

Intracerebral hemorrhage (ICH) is a major public health challenge worldwide, and is associated with elevated rates of mortality, disability, and morbidity, especially in low- and middle-income nations. However, our knowledge of the detailed molecular processes involved in ICH remains insufficient, particularly those involved in the secondary injury stage, resulting in a lack of effective treatments for ICH. Human platelet lysates (HPL) are abundant in bioactive factors, and numerous studies have demonstrated their beneficial effects on neurological diseases, including their anti-neuroinflammatory ability, anti-oxidant effects, maintenance of blood–brain barrier integrity, and promotion of neurogenesis. In this review, we thoroughly explore the potential of HPL for treating ICH from three critical perspectives: the rationale for selecting HPL as a treatment for ICH, the mechanisms through which HPL contributes to ICH management, and the additional measures necessary for HPL as a treatment for ICH. We elucidate the role of platelets in ICH pathophysiology and highlight the limitations of the current treatment options and advancements in preclinical research on the application of HPL in neurological disorders. Furthermore, historical developments and preparation methods of HPL in the field of biomedicine are discussed. Additionally, we summarize the bioactive molecules present in HPL and their potential therapeutic effects in ICH. Finally, we outline the issues that must be addressed regarding utilizing HPL as a treatment modality for ICH.

The impact of serum uric acid (SUA) trajectories on the development of retinal arteriosclerosis is uncertain. The purpose of this study was to identify adult SUA trajectories by sex and determine their association with risk of retinal arteriosclerosis. In this longitudinal study, 4,324 participants who were aged between 18 and 60 years without retinal arteriosclerosis at or before baseline (from January 1, 2010, through December 31, 2010) were included. Group-based trajectory modeling was used to identify SUA trajectories during the exposure period (from January 1, 2006, through December 31, 2010). Cox proportional-hazards models were applied to evaluate the associations between SUA trajectories and the risk of incident retinal arteriosclerosis during the outcome period (from January 1, 2011, through December 31, 2019). 4 distinct SUA trajectories were identified in both women and men: low, moderate, moderate-high, and high. During a median follow-up of 9.54 years (IQR 9.53-9.56), 97 women and 295 men had developed retinal arteriosclerosis. In the fully adjusted model, a significant association between the moderate-high SUA trajectory group and incidence of retinal arteriosclerosis was observed only in men (HR: 1.76, 95% CI: 1.17-2.65) compared with the low trajectory group, but not in women (HR: 0.77, 95% CI: 0.39-1.52). Also, the high SUA trajectory group had the highest risk with an adjusted HR of 1.81 (95% CI, 1.04-3.17) in men. However, they did not exhibit a substantially increased risk in women. Higher SUA trajectory groups were significantly associated with an increased risk of incident retinal arteriosclerosis in men but not in women.

Background High-dimensional omics data are increasingly utilized in clinical and public health research for disease risk prediction. Many previous sparse methods have been proposed that using prior knowledge, e.g., biological group structure information, to guide the model-building process. However, these methods are still based on a single model, offen leading to overconfident inferences and inferior generalization. Results We proposed a novel stacking strategy based on a non-negative spike-and-slab Lasso (nsslasso) generalized linear model (GLM) for disease risk prediction in the context of high-dimensional omics data. Briefly, we used prior biological knowledge to segment omics data into a set of sub-data. Each sub-model was trained separately using the features from the group via a proper base learner. Then, the predictions of sub-models were ensembled by a super learner using nsslasso GLM. The proposed method was compared to several competitors, such as the Lasso, grlasso, and gsslasso, using simulated data and two open-access breast cancer data. As a result, the proposed method showed robustly superior prediction performance to the optimal single-model method in high-noise simulated data and real-world data. Furthermore, compared to the traditional stacking method, the proposed nsslasso stacking method can efficiently handle redundant sub-models and identify important sub-models. Conclusions The proposed nsslasso method demonstrated favorable predictive accuracy, stability, and biological interpretability. Additionally, the proposed method can also be used to detect new biomarkers and key group structures.

Our objective is to develop a prognostic model focused on cuproptosis, aimed at predicting overall survival (OS) outcomes among Acute myeloid leukemia (AML) patients. The model utilized machine learning algorithms incorporating stacking. The GSE37642 dataset was used as the training data, and the GSE12417 and TCGA-LAML cohorts were used as the validation data. Stacking was used to merge the three prediction models, subsequently using a random survival forests algorithm to refit the final model using the stacking linear predictor and clinical factors. The prediction model, featuring stacking linear predictor and clinical factors, achieved AUC values of 0.840, 0.876 and 0.892 at 1, 2 and 3 years within the GSE37642 dataset. In external validation dataset, the corresponding AUCs were 0.741, 0.754 and 0.783. The predictive performance of the model in the external dataset surpasses that of the model simply incorporates all predictors. Additionally, the final model exhibited good calibration accuracy. In conclusion, our findings indicate that the novel prediction model refines the prognostic prediction for AML patients, while the stacking strategy displays potential for model integration.

The interleukins (ILs) are a pluripotent cytokine family that have been reported to regulate ischemic stroke and cerebral ischemia/reperfusion (I/R) injury. IL-22 is a member of the IL-10 superfamily and plays important roles in tissue injury and repair. However, the effects of IL-22 on ischemic stroke and cerebral I/R injury remain unclear. In the current study, we provided direct evidence that IL-22 treatment decreased infarct size, neurological deficits, and brain water content in mice subjected to cerebral I/R injury. IL-22 treatment remarkably reduced the expression of inflammatory cytokines, including IL-1β, monocyte chemotactic protein- (MCP-) 1, and tumor necrosis factor- (TNF-) α, both in serum and the ischemic cerebral cortex. In addition, IL-22 treatment also decreased oxidative stress and neuronal apoptosis in mice after cerebral I/R injury. Moreover, IL-22 treatment significantly increased Janus tyrosine kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 phosphorylation levels in mice and PC12 cells, and STAT3 knockdown abolished the IL-22-mediated neuroprotective function. These findings suggest that IL-22 might be exploited as a potential therapeutic agent for ischemic stroke and cerebral I/R injury.

To investigate the gender-specific relationship between total bilirubin (TBIL) and fundus arteriosclerosis in the general population, and to explore whether there is a dose–response relationship between them. In a retrospective cohort study, 27,477 participants were enrolled from 2006 to 2019. The TBIL was divided into four groups according to the quartile. The Cox proportional hazards model was used to estimate the HRs with 95% CIs of different TBIL level and fundus arteriosclerosis in men and women. The dose–response relationship between TBIL and fundus arteriosclerosis was estimated using restricted cubic splines method. In males, after adjusting for potential confounders, the Q2 to Q4 level of TBIL were significantly associated with the risk of fundus arteriosclerosis. The HRs with 95% CIs were 1.217 (1.095–1.354), 1.255 (1.128–1.396) and 1.396 (1.254–1.555), respectively. For females, TBIL level was not associated with the incidence of fundus arteriosclerosis. In addition, a linear relationship between TBIL and fundus arteriosclerosis in both genders ( P  < 0.0001 and P  = 0.0047, respectively). In conclusion, the incidence of fundus arteriosclerosis is positively correlated with serum TBIL level in males, but not in females. In addition, there was a linear dose–response relationship between TBIL and incidence of fundus arteriosclerosis.

Background The number of residents at high altitude is high globally, yet few studies have been conducted on the association between altitude and incident frailty. We evaluated the prospective association and dose-response relationship between altitude and frailty among Chinese older adults. Methods We conducted a prospective cohort study using data from the China Health and Retirement Longitudinal Survey (CHARLS) from 2013 to 2018, enrolling 4065 participants aged ≥ 60 years at baseline. Frailty was assessed using a frailty index (FI) containing 29 health deficit indicators constructed. Cox proportional hazard regression and linear mixed model were used to analyze the association of altitude with frailty. Restricted Cubic Spline regression was used to assess the dose-response relationship between them. Results After a median follow-up of 61 months, 1076 (26.5%) frailty events were documented, including 137 (32.2%) in the middle and 939 (25.8%) in the low altitude group. The FI in the middle altitude group was higher than that in the low altitude group at three waves (baseline = 2013, wave 1 = 2015, and wave 2 = 2018 years). The risk of incident frailty was increased by 24% (HR = 1.24, 95%CI: 1.03–1.48) in the middle altitude group compared to the low altitude group. The FI increased with increasing altitude. The RCS revealed an increased risk of developing frailty at altitudes above 2,000 m. Conclusions Exposure to high altitude is associated with an elevated risk of incident frailty. which suggested that early intervention with high-altitude residents can delay frailty.

Background PDGFRA genetic alterations are a well-established oncogenic driver in gliomas. However, targeted monotherapy against PDGFRA such as avapritinib has achieved limited clinical efficacy, and the mechanism underlying avapritinib resistance remains poorly understood. Methods Multi-omics analysis of clinical samples identified super-enhancer (SE) complex components. Comprehensive preclinical evaluation was performed using glioma cell lines, glioma stem cells, patient-derived cells, xenografts, and organoids. Mechanistic investigations integrated Cleavage Under Targets and Tagmentation, chromatin immunoprecipitation, co-immunoprecipitation, mass spectrometry, protein fragment complementation, and dual-luciferase reporter assays. Results Functional and clinical analyses identified the SE complex component MED8 as significantly upregulated in gliomas and correlated with poor prognosis. MED8 was essential for tumor proliferation and survival both in vitro and in vivo. Mechanistically, MED8 cooperated with CDK7 to bind and activate the SEs of PDGFRA, sustaining high transcriptional output of this oncogene. We repurposed FDA-approved venetoclax as a first-in-class MED8-targeting agent that potently sensitizes to avapritinib, exerting synergistic effects in multiple preclinical models. Conclusions This study delineates a novel MED8-SE-PDGFRA epigenetic axis driving resistance. The combination of avapritinib and venetoclax, co-targeting the oncogenic signal and its transcriptional regulator, presents a translatable dual-targeting strategy to improve outcomes in PDGFRA-driven glioma.