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Abstract The cGAS-STING pathway plays a crucial role in anti-tumoral responses by activating inflammation and reprogramming the tumour microenvironment. Upon activation, STING traffics from the endoplasmic reticulum (ER) to Golgi, allowing signalling complex assembly and induction of interferon and inflammatory cytokines. Here we report that cGAMP stimulation leads to a transient decline in ER cholesterol levels, mediated by Sterol O-Acyltransferase 1-dependent cholesterol esterification. This facilitates ER membrane curvature and STING trafficking to Golgi. Notably, we identify two cholesterol-binding motifs in STING and confirm their contribution to ER-retention of STING. Consequently, depletion of intracellular cholesterol levels enhances STING pathway activation upon cGAMP stimulation. In a preclinical tumour model, intratumorally administered cholesterol depletion therapy potentiated STING-dependent anti-tumoral responses, which, in combination with anti-PD-1 antibodies, promoted tumour remission. Collectively, we demonstrate that ER cholesterol sets a threshold for STING signalling through cholesterol-binding motifs in STING and we propose that this could be exploited for cancer immunotherapy.

Background. The pineal region represents significant challenges in terms of neurosurgery. Currently, anatomical research that simulates surgery for the endoscopic keyhole approach to the pineal region is lacking. This study aims to summarize the exposure range and operational characteristics of total endoscopic surgery under the four supratentorial and infratentorial keyhole approaches, through rigorous quantitative anatomical research. We also aim to understand the surgical exposure characteristics and surgical feasibility under each approach. Method. Six wet cadaveric head specimens (a total of 12 sides) were subjected to simulated surgery with a keyhole bone window size of approximately 3 × 4 cm. The median endoscopic supracerebellar infratentorial approach (M-ESCITA), the paramedian endoscopic supracerebellar infratentorial approach (PM-ESCITA), the endoscopic occipital transtentorial approach (EOTA), and the endoscopic interhemispheric high occipital transtentorial approach (EHOTA) were used to measure the surgical path depth, maximum distance between the tentorial margins, maximum operable area, operable angle, and relative degree of freedom of each approach. Results. There was no difference in the exposure range of the surgical area. The surgical path of PM-ESCITA was the longest (p

Abstract Background Low-grade gliomas (LGG) are a type of brain tumor that can be lethal, and it is essential to identify genes that are correlated with patient prognosis. In this study, we aimed to use CRISPR-cas9 screening data to identify key signaling pathways and develop a genetic signature associated with high-risk, low-grade glioma patients. Methods The study used CRISPR-cas9 screening data to identify essential genes correlated with cell survival in LGG. We used RNA-seq data to identify differentially expressed genes (DEGs) related to cell viability. Moreover, we used the least absolute shrinkage and selection operator (LASSO) method to construct a genetic signature for predicting overall survival in patients. We performed enrichment analysis to identify pathways mediated by DEGs, overlapping genes, and genes shared in the Weighted correlation network analysis (WGCNA). Finally, the study used western blot, qRT-PCR, and IHC to detect the expression of hub genes from signature in clinical samples. Results The study identified 145 overexpressed oncogenes in low-grade gliomas using the TCGA database. These genes were intersected with lethal genes identified in the CRISPR-cas9 screening data from Depmap database, which are enriched in Hippo pathways. A total of 19 genes were used to construct a genetic signature, and the Hippo signaling pathway was found to be the predominantly enriched pathway. The signature effectively distinguished between low- and high-risk patients, with high-risk patients showing a shorter overall survival duration. Differences in hub gene expression were found in different clinical samples, with the protein and mRNA expression of REP65 being significantly up-regulated in tumor cells. The study suggests that the Hippo signaling pathway may be a critical regulator of viability and tumor proliferation and therefore is an innovative new target for treating cancerous brain tumors, including low-grade gliomas. Conclusion Our study identified a novel genetic signature associated with high-risk, LGG patients. We found that the Hippo signaling pathway was significantly enriched in this signature, indicating that it may be a critical regulator of tumor viability and proliferation in LGG. Targeting the Hippo pathway could be an innovative new strategy for treating LGG.

Cerebral vasospasm (CVS) is the most common neurological complication after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome and mortality. Reports on incidence and predictors of CVS in Chinese patients with aSAH were scarce. We aimed to estimate the incidence and predictors of angiographic vasospasm (AV), symptomatic vasospasm (SV), and cerebral infarction in Chinese patients with aSAH.We retrospectively reviewed the medical records of 542 consecutive aSAH patients admitted to neurosurgery department of the First Affiliated Hospital of Xinjiang Medical University in Urumqi city of China between January 1, 2011 and December 31, 2015. AV, SV and cerebral infarction were defined based on clinical data and neuroimaging findings. Univariate and multivariate analyses were performed to identify predictors of AV, SV or cerebral infarction.343 (63.3%) patients fulfilled the inclusion and exclusion criteria. Of them, 182(53.1%) developed AV, 99 (28.9%) developed SV, and 87 (25.4%) developed cerebral infarction. A history of hypertension, poor modified Fisher grade (3-4) and poor Hunt-Hess grade (4-5) on admission were common risk factors for AV, SV and cerebral infarction. Patients from Uyghur ethnic group or other minorities were less likely to develop AV, SV or cerebral infarction, compared to those from Han ethic group after adjustment of other potential confounders. Additionally, age ≥53 years, leukocyte count ≥11× 109/L on admission and being current or former smokers were independent risk factors of cerebral infarction. Leukocyte count ≥11× 109/L on admission and aneurysm size ≥ 10 mm were independent risk factors of SV. Serum glucose level ≥7.0 mmol/L on admission was an independent risk factor of AV.Risk factors of different definitions of CVS were diverse in Chinese patients with aSAH; however, risk factors of SV and cerebral infarction seem to be similar. We recommend early and aggressive therapy in these patients at-risk of CVS.

The brain is highly sensitive to damage caused by infection and inflammation 1,2 . Herpes simplex virus 1 (HSV-1) is a neurotropic virus and the cause of herpes simplex encephalitis 3 . It is unknown whether neuron-specific antiviral factors control virus replication to prevent infection and excessive inflammatory responses, hence protecting the brain. Here we identify TMEFF1 as an HSV-1 restriction factor using genome-wide CRISPR screening. TMEFF1 is expressed specifically in neurons of the central nervous system and is not regulated by type I interferon, the best-known innate antiviral system controlling virus infections. Depletion of TMEFF1 in stem-cell-derived human neurons led to elevated viral replication and neuronal death following HSV-1 infection. TMEFF1 blocked the HSV-1 replication cycle at the level of viral entry through interactions with nectin-1 and non-muscle myosin heavy chains IIA and IIB, which are core proteins in virus-cell binding and virus-cell fusion, respectively 4-6 . Notably, Tmeff1 -/- mice exhibited increased susceptibility to HSV-1 infection in the brain but not in the periphery. Within the brain, elevated viral load was observed specifically in neurons. Our study identifies TMEFF1 as a neuron-specific restriction factor essential for prevention of HSV-1 replication in the central nervous system., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Investigate the potential correlation between the age of initial sexual contact, the lifetime accumulation of sexual partners, and the occurrence of intracranial aneurysm (IA) employing a two-sample Mendelian randomization approach., Methods: This research aims to elucidate the causal relationship between intracranial aneurysm (IA) and sexual variables. Two distinct sexual variables, specifically the age had first sexual intercourse ( n = 406,457) and the lifetime number of sexual partners ( n = 378,882), were employed as representative parameters in a two-sample Mendelian randomization (MR) study. Outcome data from 23 cohorts, comprising 5,140 cases and 71,934 controls, were gathered through genome-wide association studies (GWAS). To bolster analytical rigor, five distinct methodologies were applied, encompassing MR-Egger technique, weighted median, inverse variance weighted, simple modeling, and weighted modeling., Results: Our investigation unveiled a causal relationship between the age first had sexual intercourse and the occurrence of intracranial aneurysm (IA), employing the Inverse Variance Weighted (IVW) approach [Odds Ratio (OR): 0.609, p -value: 5.684E-04, 95% Confidence Interval (CI): 0.459-0.807]. This association was notably significant in the context of unruptured intracranial aneurysms (uIA) using the IVW approach (OR: 0.392, p -value: 6.414E-05, 95% CI: 0.248-0.621). Conversely, our findings did not reveal any discernible link between the lifetime number of sexual partners and the occurrence of IA (IA group: OR: 1.346, p -value: 0.415, 95% CI: 0.659-2.749; SAH group: OR: 1.042, p -value: 0.943, 95% CI: 0.338-3.209; uIA group: OR: 1.990, p -value: 0.273, 95% CI: 0.581-6.814)., Conclusion: The two-sample Mendelian Randomization (MR) study presented herein provides evidence supporting a correlation between the age of initial engagement in sexual activity and the occurrence of intracranial aneurysm (IA), with a noteworthy emphasis on unruptured intracranial aneurysms (uIA). Nevertheless, our investigation failed to establish a definitive association between IA and the cumulative lifetime number of sexual partners., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Akram, Wu, Kadeer, Aisha, Cheng, Wang and Maimaiti.)

Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: The risk of intracranial aneurysms (IAs) is increased in individuals with depression and anxiety. This indicates that depression and anxiety may contribute to the development of physical disorders. Herein, to investigate the association between genetic variants related to depression and anxiety and the risk of IA, two-sample Mendelian randomization was performed., Methods: The genome-wide association study (GWAS) comprised genome-wide genotype data of 2248 clinically well-characterized patients with anxiety and 7992 ethnically matched controls from four European countries. Sex-specific summary-level outcome data were obtained from the GWAS of IA, including 23 cohorts with a total of 10,754 cases and 306,882 controls of European and East Asian ancestry. To improve validity, five varying Mendelian randomization techniques were used in the analysis, namely Mendelian randomization-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode., Results: The inverse variance weighted results indicated the causal effect of depression on IA (P = 0.03, OR = 1.32 [95 % CI, 1.03-1.70]) and unruptured IA (UIA) (P = 0.02, OR = 1.68 [95 % CI, 1.08-2.61]). However, the causal relationship between depression and subarachnoid hemorrhage (SAH) was not found (P = 0.16). We identified 43 anxiety-associated single-nucleotide polymorphisms as genetic instruments and found no causal relationship between anxiety and IA, UIA, and SAH., Limitations: Potential pleiotropy, possible weak instruments, and low statistical power limited our findings., Conclusion: Our MR study suggested a possible causal effect of depression on the increased risk of UIAs. Future research is required to investigate whether rational intervention in depression treatment can help to decrease the societal burden of IAs., Competing Interests: Declaration of competing interest All authors declare that they have no financial interests and personal relationships that can inappropriately influence our work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The cGAS-STING pathway plays a crucial role in anti-tumoral responses by activating inflammation and reprogramming the tumour microenvironment. Upon activation, STING traffics from the endoplasmic reticulum (ER) to Golgi, allowing signalling complex assembly and induction of interferon and inflammatory cytokines. Here we report that cGAMP stimulation leads to a transient decline in ER cholesterol levels, mediated by Sterol O-Acyltransferase 1-dependent cholesterol esterification. This facilitates ER membrane curvature and STING trafficking to Golgi. Notably, we identify two cholesterol-binding motifs in STING and confirm their contribution to ER-retention of STING. Consequently, depletion of intracellular cholesterol levels enhances STING pathway activation upon cGAMP stimulation. In a preclinical tumour model, intratumorally administered cholesterol depletion therapy potentiated STING-dependent anti-tumoral responses, which, in combination with anti-PD-1 antibodies, promoted tumour remission. Collectively, we demonstrate that ER cholesterol sets a threshold for STING signalling through cholesterol-binding motifs in STING and we propose that this could be exploited for cancer immunotherapy., (© 2024. The Author(s).)

Current differentiation protocols for generating mesencephalic dopaminergic (mesDA) neurons from human pluripotent stem cells result in grafts containing only a small proportion of mesDA neurons when transplanted in vivo. In this study, we develop lineage-restricted undifferentiated stem cells (LR-USCs) from pluripotent stem cells, which enhances their potential for differentiating into caudal midbrain floor plate progenitors and mesDA neurons. Using a ventral midbrain protocol, 69% of LR-USCs become bona fide caudal midbrain floor plate progenitors, compared to only 25% of human embryonic stem cells (hESCs). Importantly, LR-USCs generate significantly more mesDA neurons under midbrain and hindbrain conditions in vitro and in vivo. We demonstrate that midbrain-patterned LR-USC progenitors transplanted into 6-hydroxydopamine-lesioned rats restore function in a clinically relevant non-pharmacological behavioral test, whereas midbrain-patterned hESC-derived progenitors do not. This strategy demonstrates how lineage restriction can prevent the development of undesirable lineages and enhance the conditions necessary for mesDA neuron generation., (© 2023. The Author(s).)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Autophagy is considered a double-edged sword, with a role in the regulation of the pathophysiological processes of the central nervous system (CNS) after cerebral ischemia-reperfusion injury (CIRI). The 18-kDa translocator protein (TSPO) is a highly conserved protein, with its expression level in the nervous system closely associated with the regulation of pathophysiological processes. In addition, the ligand of TSPO reduces neuroinflammation in brain diseases, but the potential role of TSPO in CIRI is largely undiscovered. On this basis, we investigated whether TSPO regulates neuroinflammatory response by affecting autophagy in microglia. In our study, increased expression of TSPO was detected in rat brain tissues with transient middle cerebral artery occlusion (tMCAO) and in BV2 microglial cells exposed to oxygen-glucose deprivation or reoxygenation (OGD/R) treatment, respectively. In addition, we confirmed that autophagy was over-activated during CIRI by increased expression of autophagy activation related proteins with Beclin-1 and LC3B, while the expression of p62 was decreased. The degradation process of autophagy was inhibited, while the expression levels of LAMP-1 and Cathepsin-D were significantly reduced. Results of confocal laser microscopy and transmission electron microscopy (TEM) indicated that autophagy flux was disordered. In contrast, inhibition of TSPO prevented autophagy over-activation both in vivo and in vitro. Interestingly, suppression of TSPO alleviated nerve cell damage by reducing reactive oxygen species (ROS) and pro-inflammatory factors, including TNF-α and IL-6 in microglia cells. In summary, these results indicated that TSPO might affect CIRI by mediating autophagy dysfunction and thus might serve as a potential target for ischemic stroke treatment., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Circular RNAs (circRNAs) are key regulators of cellular processes, are abundant in the nervous system, and have putative regulatory roles during neural differentiation. However, the knowledge about circRNA functions in brain development is limited. Here, using RNA-sequencing, we show that circRNA levels increased substantially over the course of differentiation of human embryonic stem cells into rostral and caudal neural progenitor cells (NPCs), including three of the most abundant circRNAs, ciRS-7, circRMST, and circFAT3. Knockdown of circFAT3 during early neural differentiation resulted in minor transcriptional alterations in bulk RNA analysis. However, single-cell transcriptomics of 30 and 90 days differentiated cerebral organoids deficient in circFAT3 showed a loss of telencephalic radial glial cells and mature cortical neurons, respectively. Furthermore, non-telencephalic NPCs in cerebral organoids showed changes in the expression of genes involved in neural differentiation and migration, including FAT4, ERBB4, UNC5C, and DCC. In vivo depletion of circFat3 in mouse prefrontal cortex using in utero electroporation led to alterations in the positioning of the electroporated cells within the neocortex. Overall, these findings suggest a conserved role for circFAT3 in neural development involving the formation of anterior cell types, neuronal differentiation, or migration., (© 2023. The Author(s).)

Background: Low-grade gliomas (LGG) are a type of brain tumor that can be lethal, and it is essential to identify genes that are correlated with patient prognosis. In this study, we aimed to use CRISPR-cas9 screening data to identify key signaling pathways and develop a genetic signature associated with high-risk, low-grade glioma patients., Methods: The study used CRISPR-cas9 screening data to identify essential genes correlated with cell survival in LGG. We used RNA-seq data to identify differentially expressed genes (DEGs) related to cell viability. Moreover, we used the least absolute shrinkage and selection operator (LASSO) method to construct a genetic signature for predicting overall survival in patients. We performed enrichment analysis to identify pathways mediated by DEGs, overlapping genes, and genes shared in the Weighted correlation network analysis (WGCNA). Finally, the study used western blot, qRT-PCR, and IHC to detect the expression of hub genes from signature in clinical samples., Results: The study identified 145 overexpressed oncogenes in low-grade gliomas using the TCGA database. These genes were intersected with lethal genes identified in the CRISPR-cas9 screening data from Depmap database, which are enriched in Hippo pathways. A total of 19 genes were used to construct a genetic signature, and the Hippo signaling pathway was found to be the predominantly enriched pathway. The signature effectively distinguished between low- and high-risk patients, with high-risk patients showing a shorter overall survival duration. Differences in hub gene expression were found in different clinical samples, with the protein and mRNA expression of REP65 being significantly up-regulated in tumor cells. The study suggests that the Hippo signaling pathway may be a critical regulator of viability and tumor proliferation and therefore is an innovative new target for treating cancerous brain tumors, including low-grade gliomas., Conclusion: Our study identified a novel genetic signature associated with high-risk, LGG patients. We found that the Hippo signaling pathway was significantly enriched in this signature, indicating that it may be a critical regulator of tumor viability and proliferation in LGG. Targeting the Hippo pathway could be an innovative new strategy for treating LGG., (© 2023. The Author(s).)

Lower WHO grade II and III gliomas (LGGs) exhibit significant genetic and transcriptional heterogeneity, and the heterogeneity of DNA damage repair (DDR) and its relationship to tumor biology, transcriptome, and tumor microenvironment (TME) remains poorly understood. In this study, we conducted multi-omics data integration to investigate DDR alterations in LGG. Based on clinical parameters and molecular characteristics, LGG patients were categorized into distinct DDR subtypes, namely, DDR-activated and DDR-suppressed subtypes. We compared gene mutation, immune spectrum, and immune cell infiltration between the two subtypes. DDR scores were generated to classify LGG patients based on DDR subtype features, and the results were validated using a multi-layer data cohort. We found that DDR activation was associated with poorer overall survival and that clinicopathological features of advanced age and higher grade were more common in the DDR-activated subtype. DDR-suppressed subtypes exhibited more frequent mutations in IDH1. In addition, we observed significant upregulation of activated immune cells in the DDR-activated subgroup, which suggests that immune cell infiltration significantly influences tumor progression and immunotherapeutic responses. Furthermore, we constructed a DDR signature for LGG using six DDR genes, which allowed for the division of patients into low- and high-risk groups. Quantitative real-time PCR results showed that CDK1, CDK2, TYMS, SMC4, and WEE1 were significantly upregulated in LGG samples compared to normal brain tissue samples. Overall, our study sheds light on DDR heterogeneity in LGG and provides insight into the molecular pathways of DDR involved in LGG development., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: Immunogenic Cell Death (ICD) is a novel way to regulate cell death and can sufficiently activate adaptive immune responses. Its role in immunity is still emerging. However, the involvement of ICD in Intracranial Aneurysms (IA) remains unclear. This study aimed to identify biomarkers associated with ICDs and determine the relationship between them and the immune microenvironment during the onset and progression of IA., Methods: The IA gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in IA were identified and the effects of the ICD on immune microenvironment signatures were studied. Techniques like Lasso, Bayes, DT, FDA, GBM, NNET, RG, SVM, LR, and multivariate analysis were used to identify the ICD gene signatures in IA. A consensus clustering algorithm was used for conducting the unsupervised cluster analysis of the ICD patterns in IA. Furthermore, enrichment analysis was carried out for investigating the various immune responses and other functional pathways. Along with functional annotation, the weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network and module construction, identification of the hub gene, and co-expression analysis were also carried out., Results: The above techniques were used for establishing the ICD gene signatures of HMGB1, HMGN1, IL33, BCL2, HSPA4, PANX1, TLR9, CLEC7A, and NLRP3 that could easily distinguish IA from normal samples. The unsupervised cluster analysis helped in identifying three ICD gene patterns in different datasets. Gene enrichment analysis revealed that the IA samples showed many differences in pathways such as the cytokine-cytokine receptor interaction, regulation of actin cytoskeleton, chemokine signaling pathway, NOD-like receptor signaling pathway, viral protein interaction with the cytokines and cytokine receptors, and a few other signaling pathways compared to normal samples. In addition, the three ICD modification modes showed obvious differences in their immune microenvironment and the biological function pathways. Eight ICD-regulators were identified and showed meaningful associations with IA, suggesting they could severe as potential prognostic biomarkers., Conclusions: A new gene signature for IA based on ICD features was created. This signature shows that the ICD pattern and the immune microenvironment are closely related to IA and provide a basis for optimizing risk monitoring, clinical decision-making, and developing novel treatment strategies for patients with IA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Turhon, Maimaiti, Gheyret, Axier, Rexiati, Kadeer, Su, Wang, Chen, Cheng, Zhang and Aisha.)

Background: The role of epigenetic modulation in immunity is receiving increased recognition-particularly in the context of RNA N6-methyladenosine (m6A) modifications. Nevertheless, it is still uncertain whether m6A methylation plays a role in the onset and progression of intracranial aneurysms (IAs). This study aimed to establish the function of m6A RNA methylation in IA, as well as its correlation with the immunological microenvironment., Methods: Our study included a total of 97 samples (64 IA, 33 normal) in the training set and 60 samples (44 IA, 16 normal) in the validation set to systematically assess the pattern of RNA modifications mediated by 22 m6A regulators. The effects of m6A modifications on immune microenvironment features, i.e., immune response gene sets, human leukocyte antigen (HLA) genes, and infiltrating immune cells were explored. We employed Lasso, machine learning, and logistic regression for the purpose of identifying an m6A regulator gene signature of IA with external data validation. For the unsupervised clustering analysis of m6A modification patterns in IA, consensus clustering methods were employed. Enrichment analysis was used to assess immune response activity along with other functional pathways. The identification of m6A methylation markers was identified based on a protein-protein interaction network and weighted gene co-expression network analysis., Results: We identified an m6A regulator signature of IGFBP2, IGFBP1, IGF2BP2, YTHDF3, ALKBH5, RBM15B, LRPPRC , and ELAVL1 , which could easily distinguish individuals with IA from healthy individuals. Unsupervised clustering revealed three m6A modification patterns. Gene enrichment analysis illustrated that the tight junction, p53 pathway, and NOTCH signaling pathway varied significantly in m6A modifier patterns. In addition, the three m6A modification patterns showed significant differences in m6A regulator expression, immune microenvironment, and bio-functional pathways. Furthermore, macrophages, activated T cells, and other immune cells were strongly correlated with m6A regulators. Eight m6A indicators were discovered-each with a statistically significant correlation with IA-suggesting their potential as prognostic biological markers., Conclusion: Our study demonstrates that m6A RNA methylation and the immunological microenvironment are both intricately correlated with the onset and progression of IA. The novel insight into patterns of m6A modification offers a foundation for the development of innovative treatment approaches for IA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maimaiti, Turhon, Cheng, Su, Kadeer, Axier, Ailaiti, Aili, Abudusalamu, Kuerban, Wang and Aisha.)

Objective: In this study, the hemodynamic parameters of ruptured intracranial aneurysms (IAs) in various studies were summarized and analyzed to provide predictive parameters for IA rupture in clinical work., Methods: We searched PubMed, Web of science, Embase, and Cochrane databases for articles published before December 2021 to collect data on hemodynamic parameters associated with IA rupture. Differences in wall shear stress (WSS), oscillatory shear index (OSI), and low wall shear stress area (LSA) between ruptured and unruptured IAs in the literature were summarized and analyzed, and the standardized mean difference (SMD) of 95% CI was calculated by Review Manager 5.3., Results: By searching and screening the literature, this meta-analysis included 17 studies comprising 1,373 IA patients. In the ruptured aneurysm group, the level of WSS decreased significantly, while OSI and LSA increased obviously., Conclusion: Low WSS, high OSI, and high LSA are closely related to the rupture of IAs, indicating the role of WSS, OSI, and LSA as important hemodynamic parameters for predicting the rupture of IAs in clinical work., Competing Interests: None., (AJTR Copyright © 2022.)

Autophagy is a highly conserved lysosomal degradation process essential in tumorigenesis. However, the involvement of autophagy-related long noncoding RNAs (lncRNAs) in low-grade glioma (LGG) remains unclear. In this study, we established an autophagy-related lncRNA prognostic signature for patients with LGG and assess its underlying functions. We used univariate Cox, least absolute shrinkage and selection operator and multivariate Cox regression models to establish an autophagy-related lncRNA prognostic signature. Kaplan-Meier survival analysis, receiver operating characteristic curve, nomogram, C-index, calibration curve and clinical decision-making curve were used to assess the predictive capability of the identified signature. A signature comprising nine autophagy-related lncRNAs (AL136964.1, ARHGEF26-AS1, PCED1B-AS1, AS104072.1, PRKCQ-AS1, LINC00957, AS125616.1, PSMB8-AS1 and AC087741.1) was identified as a prognostic model. Patients with LGG were divided into the high- and low-risk cohorts based on the median model-based risk score. The survival analysis revealed a 10-year survival rate of 9.3% (95% CI 1.91-45.3%) and 13.48% (95% CI 4.52-40.2%) in high-risk patients in the training and validation sets, respectively, and 48.4% (95% CI 24.7-95.0%) and 48.4% (95% CI 28.04-83.4%) in low-risk patients in the training and validation sets, respectively. This finding suggested a relatively low survival in high-risk patients. In addition, the lncRNA signature was independently prognostic and potentially associated with the progression of LGG. Therefore, the 9-autophagy-related-lncRNA signature may play a crucial role in the diagnosis and treatment of LGG, which may offer new avenues for tumour-targeted therapy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: DNA methylation is an important epigenetic modification that affects genomic instability and regulates gene expression. Long non-coding RNAs (lncRNAs) modulate gene expression by interacting with chromosomal modifications or remodelling factors. It is urgently needed to evaluate the effects of DNA methylation-related lncRNAs (DMlncRNAs) on genome instability and further investigate the mechanism of action of DMlncRNAs in mediating the progression of lower-grade gliomas (LGGs) and their impact on the immune microenvironment. Methods: LGG transcriptome data, somatic mutation profiles and clinical features analysed in the present study were obtained from the CGGA, GEO and TCGA databases. Univariate, multivariate Cox and Lasso regression analyses were performed to establish a DMlncRNA signature. The KEGG and GO analyses were performed to screen for pathways and biological functions associated with key genes. The ESTIMATE and CIBERSORT algorithms were used to determine the level of immune cells in LGGs and the immune microenvironment fraction. In addition, DMlncRNAs were assessed using survival analysis, ROC curves, correlation analysis, external validation, independent prognostic analysis, clinical stratification analysis and qRT-PCR. Results: We identified five DMlncRNAs with prognostic value for LGGs and established a prognostic signature using them. The Kaplan-Meier analysis revealed 10-years survival rate of 10.10% [95% confidence interval (CI): 3.27-31.40%] in high-risk patients and 57.28% (95% CI: 43.17-76.00%) in low-risk patients. The hazard ratio (HR) and 95% CI of risk scores were 1.013 and 1.009-1.017 ( p < 0.001), respectively, based on the univariate Cox regression analysis and 1.009 and 1.004-1.013 ( p < 0.001), respectively, based on the multivariate Cox regression analysis. Therefore, the five-lncRNAs were identified as independent prognostic markers for patients with LGGs. Furthermore, GO and KEGG analyses revealed that these lncRNAs are involved in the prognosis and tumorigenesis of LGGs by regulating cancer pathways and DNA methylation. Conclusion: The findings of the study provide key information regarding the functions of lncRNAs in DNA methylation and reveal that DNA methylation can regulate tumour progression through modulation of the immune microenvironment and genomic instability. The identified prognostic lncRNAs have high potential for clinical grouping of patients with LGGs to ensure effective treatment and management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maimaiti, Aili, Turhon, Kadeer, Aikelamu, Wang, Niu, Aisha, Kasimu, Wang and Wang.)

The differentiation of patient-specific induced pluripotent stem cells (iPSCs) into specific neuronal subtypes has been exploited as an approach for modeling a variety of neurological disorders. However, achieving a highly pure population of neurons is challenging when using directed differentiation methods, especially for neuronal subtypes generated by complex and protracted protocols. In this study, we efficiently produced highly pure populations of regionally specified CNS neurons by using a modified NGN2-Puromycin direct conversion protocol. The protocol is amenable across a range of iPSC lines, with more than 95% of cells at day 21 positive for the neuronal marker MAP2. We found that conversion from pluripotent stem cells resulted in neurons from the central and peripheral nervous system; however, by incorporating a short CNS patterning step, we eliminated these peripheral neurons. Furthermore, we used the patterning step to control the rostral-caudal identity. This approach of sequential patterning and conversion produced pure populations of forebrain neurons, when patterned with SMAD inhibitors. Additionally, when SMAD inhibitors and WNT agonists were applied, the approach produced anterior hindbrain excitatory neurons and resulted in a neuronal population containing VSX2/SHOX2 V2a interneurons. Overall, this sequential patterning and conversion protocol can be used for the production of a variety of CNS excitatory neurons from patient-derived iPSCs, and is a highly versatile system for investigating early disease events for a range of neurological disorders including Alzheimer's disease, motor neurons disease and spinal cord injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To introduce and evaluate a technique to precisely localize the transverse-sigmoid sinus junction (TSSJ) in retrosigmoid craniotomy. Methods: This was a single-center prospective randomized controlled study. Sixty-three patients, 29 male and 34 female, who would undergo retrosigmoid craniotomy admitted to Department of Neurosurgery, the First Affiliated Hospital of Xinjiang Medical Universityfrom March to October 2019 were enrolled in the study and were divided into trial group and control group according to the computer-generated random numbers. Preoperative venous computed tomographic angiography (CTA) combined with 3-dimensional computed tomography computed tomography (3D CT) was randomly given to the patients( n= 32). Asterion was used for identification of the TSSJ in the controls ( n= 31). The main outcome measures as postoperative complications and relevant intraoperative indicators were compared. Results: Incision length, craniotomy time, bone window sizein trial group were shorter or smaller than those of the controls, as(6.8±0.5) cm vs (8.0±1.5) cm, (37±8) min vs (45±15) min, (8.7±1.2) cm(2) vs (10.2±2.4) cm(2) respectively, with statistical significance (all P <0.05). No statistical significance was found in bleeding amount, incidence of sinus injury and cerebrospinal fluid leakage. While incidence of neck pain was lower in case group (15.63% vs 38.71%; P= 0.04) and the remission time of incisional pain in case group was shorter [(6±1) d vs (9±2) d; P= 0.01]. Conclusion: While the technique is used, the center of the keyhole should be located at transitional place of the lateral part of the occipitomastoid suture, the retromastoid ridge and the superior nuchal line. Compared with the traditional craniotomy method marked by asterion, it has great advantages in reducing incidence of postoperative complications, craniotomy time, and the remission time of incisional pain.

We generated an induced pluripotent stem cell (iPSC) line from fibroblasts of a clinically diagnosed 70 year old female Parkinson's disease (PD) patient heterozygous for a pathogenic missense variant (p.G2019S; c. 6055 G > A) in the leucine-rich repeat kinase 2 (LRRK2) gene by using non-integrating Sendai viruses. The DANi-011A iPSC line has a normal karyotype and is free from Sendai viruses. The expression of pluripotent markers in the iPSC line was confirmed by immunofluorescent staining, and we confirmed its ability to differentiate into the three germ layers. The DANi-011A iPSC line can be used for modeling PD and as a drug-screening platform., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

We generated eight induced pluripotent stem cell (iPSC) lines from Parkinson's disease (PD) patients with different familial mutations using non-integrating episomal plasmids. All iPSC lines have a normal karyotype, express pluripotent genes including POU5F1, NANOG, and show alkaline phosphatase activity, as well as the ability to differentiate into all three germ layers. These PD iPSC lines can be used for disease modeling to identify PD mechanisms and for the development or stratification of new drugs., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: This study aims to discuss the safety and short-term efficacy of endovascular treatment on high-risk patients with chronic carotid artery occlusion., Methods: A retrospective analysis was performed on the clinical data of 16 high-risk patients with chronic carotid artery occlusion who received endovascular treatment at the Department of Neurosurgery of the First Affiliated Hospital of Xinjiang Medical University from November 2013 to July 2016. The incidence of adverse events at 1 week, 30 days and six months post-operation were observed, and NIHSS was adopted to assess the neurological function of patients six months before and after the operation. Follow-up time was 6-26 months, with an average of 18.4 months., Results: The degree of carotid artery stenosis of these 16 patients was 100%. The degree of which after the operation was 24.9 ± 17.0%; and the difference was statistically significant (P<0.05). Iatrogenic carotid artery dissection occurred in one case, and persistent hypotension and sinus bradycardia occurred in one case. Furthermore, one case of endovascular treatment was not approved to be opened. Afterwards, temporal artery-STA-MCA bypass was performed; upon postoperative head CTA and DSA, the result showed that the perfusion was good. One case refused to undergo surgical treatment. The NHSS score of 14 cases of endovascular treatment that were successfully opened six months after the operation was 2.0 ± 1.36, which improved (P<0.05) compared with that of pre-operation., Conclusion: Endovascular treatment on high-risk patients with chronic carotid artery occlusion is safe and effective. And it has obvious curative effect in short mid-term., Key Words: Arterial occlusive disease, Carotid artery, Endovascular treatment, Treatment outcome.

Objective: Glioblastomais is one of the main universal, primary brain cancers, in adults, that has an extremely poor clinical prognosis and a median living period of 12-15 months, accounting for nearly 3-4% of all cancer-related deaths. MicroRNAs (miRNAs) play key roles in cancer pathogenesis by binding the specific and complementary sequences of the 3'UTR of target mRNAs to regulate protein synthesis. Therefore, recognizing functional miRNAs and the fundamental molecular mechanisms will offer novel evidences for the progress of targeted malignancy interferences. Our current study intended to explore the function of miR-28-5p in the promotion of the glioblastoma., Methods: Human glioblastoma tissues, paired nearby normal/non-tumor tissues were accumulated from our hospital. Human glioblastoma SNB19 cells were infected by miR-28-5p mimics or miR-28-5p siRNA by lentivirus. Tumor spheres formation was used to evaluate the growth ability. MTT examine was applied for measuring viability. BrdU cell proliferation assay was applied to uncover the proliferation ability of SNB19 glioblastoma cells. Real-time PCR was conducted to identify miRNA expression. Western blot analysis was employed to measure protein expression. Dual-luciferase FOXO1-3'UTR reporter was used to determine the ability of miR-28-5p to regulate FOXO1., Results: Expression of miR-28-5p was explored to be increased in both human glioblastoma tissues and cell lines. Up-regulated miR-28-5p expression promotes tumor spheres formation, cell viability, and proliferation ability of glioblastoma cells. FOXO1 was found to be the target of miR-28-5p and the activity of FOXO1 was down-regulated by miR-28-5p in glioblastoma cells., Conclusions: MiR-28-5p is an oncogene and promotes the occurrence of glioblastoma by directly targeting the FOXO1., Competing Interests: None., (IJCEP Copyright © 2019.)

Objective: To observe the short-term efficacy of Pipeline embolization divice (PED) for the treatment of complex intracranial aneurysms., Methods: The clinical data of 29 consecutive patients with 32 intracranial aneurysms treated with PED between April 2015 to September 2016 were analyzed retrospectively. There were 3 small aneurysm, 15 large aneurysms, 8 giant aneurysms, 5 fusiform ayneurysms and 1 recidivation. The vessels include 25 anterior circulation and 4 posterior circulation., Results: We treated 31 aneurysms with 30 PEDs and all of the stents were implanted successfully. 1 case of single aneurysm was multiple divices implanted and 1 case of 3 aneurysms were treated by single PED. 12 of the 29 patients were implanted PED only, 17 were implanted PED with coils, 2 underwent balloon remodeling after the PED implanted. The ostia of 19 ophthalmic arteries, 10 posterior communicating arteries, 4 posterior inferior cerebellar arteries and 1 anterior cerebral artery were covered by PED during procedures; 1 ophthalmic arteries and 1 posterior communicating artery disappeared, no branch vessels occlusion and parent artery stenosis occurred.Hemorrhagic complacations occurred in 2 patients, 2 hours and 5 days after procedure respectively. Radiographic follow-up examnations were carried out in 24 patients and revealed complete occlusion in 21 patients, uncomplete occlusion in 3 patients. No neurological injure occurred in 27 patients who received a clinical follow-up., Conclusion: PED provide a safe and effective methord for the treatment of intracranial complex aneurysms like wide-neck aneurysms, fusiform aneurysms, giant aneurysms in low risk of procedural complications and high rates of aneurysm occlusion.

Background: Hypoxia-inducible factor (HIF)-1 is involved in the regulation of hypoxic preconditioning in cardiomyocytes. Under hypoxic conditions, HIF-1α accumulates and is translocated to the nucleus, where it forms an active complex with HIF-1β and activates transcription of approximately 60 kinds of hypoxia-adaptive genes. Microtubules are hollow tubular structures in the cell that maintain cellular morphology and that transport substances. This study attempted to clarify the role of microtubule structure in the endonuclear aggregation of HIF-1α following hypoxic preconditioning of cardiomyocytes., Methods: Primary rat cardiomyocytes were isolated and cultured. The cardiomyocyte culture system was used to establish a hypoxia model and a hypoxic preconditioning model. Interventions were performed on primary cardiomyocytes using a microtubule-depolymerizing agent and different concentrations of a microtubule stabilizer. The microtubule structure and the degree of HIF-1α nuclear aggregation were observed by confocal laser scanning microscopy. The expression of HIF-1α in the cytoplasm and nucleus was detected using Western blotting. Cardiomyocyte energy content, reflected by adenosine triphosphate/adenosine diphosphate (ATP/ADP), and key glycolytic enzymes were monitored by colorimetry and high-performance liquid chromatography (HPLC). Reactive oxygen species (ROS) production was also used to comprehensively assess whether microtubule stabilization can enhance the myocardial protective effect of hypoxic preconditioning., Results: During prolonged hypoxia, it was found that the destruction of the microtubule network structure of cardiomyocytes was gradually aggravated. After this preconditioning, an abundance of HIF-1α was clustered in the nucleus. When the microtubules were depolymerized and hypoxia pretreatment was performed, HIF-1α clustering occurred around the nucleus, and HIF-1α nuclear expression was low. The levels of key glycolytic enzymes were significantly higher in the microtubule stabilizer group than in the hypoxia group. Additionally, the levels of lactate dehydrogenase and ROS were significantly lower in the microtubule stabilizer group than in the hypoxia group., Conclusion: The microtubules of cardiomyocytes may be involved in the process of HIF-1α endonuclear aggregation, helping to enhance the anti-hypoxic ability of cardiomyocytes., Competing Interests: The authors declare there are no competing interests.

Introduction: Cerebral vasospasm (CVS) is the most common neurological complication after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome and mortality. Reports on incidence and predictors of CVS in Chinese patients with aSAH were scarce. We aimed to estimate the incidence and predictors of angiographic vasospasm (AV), symptomatic vasospasm (SV), and cerebral infarction in Chinese patients with aSAH., Methods: We retrospectively reviewed the medical records of 542 consecutive aSAH patients admitted to neurosurgery department of the First Affiliated Hospital of Xinjiang Medical University in Urumqi city of China between January 1, 2011 and December 31, 2015. AV, SV and cerebral infarction were defined based on clinical data and neuroimaging findings. Univariate and multivariate analyses were performed to identify predictors of AV, SV or cerebral infarction., Results: 343 (63.3%) patients fulfilled the inclusion and exclusion criteria. Of them, 182(53.1%) developed AV, 99 (28.9%) developed SV, and 87 (25.4%) developed cerebral infarction. A history of hypertension, poor modified Fisher grade (3-4) and poor Hunt-Hess grade (4-5) on admission were common risk factors for AV, SV and cerebral infarction. Patients from Uyghur ethnic group or other minorities were less likely to develop AV, SV or cerebral infarction, compared to those from Han ethic group after adjustment of other potential confounders. Additionally, age ≥53 years, leukocyte count ≥11× 109/L on admission and being current or former smokers were independent risk factors of cerebral infarction. Leukocyte count ≥11× 109/L on admission and aneurysm size ≥ 10 mm were independent risk factors of SV. Serum glucose level ≥7.0 mmol/L on admission was an independent risk factor of AV., Conclusion: Risk factors of different definitions of CVS were diverse in Chinese patients with aSAH; however, risk factors of SV and cerebral infarction seem to be similar. We recommend early and aggressive therapy in these patients at-risk of CVS., Competing Interests: The authors have declared that no competing interests exist.

The Hippo signaling pathway plays a crucial role in suppressing tumorigenesis. Physiologically, The Hippo signaling largely restricts its two downstream effectors, homologous oncoproteins Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), to a low level of activity by the MST1-SAV1 complex-induced kinase cascade. However, how the negative regulation induced by MST1-SAV1 complex is disrupted to exhibit constitutive YAP/TAZ activation in cancer remains unclear. Herein, we reported that miR-130b directly repressed MST1 and SAV1 expression in human glioblastoma cells. Overexpression of miR-130b induced hyperactivation of the YAP/TAZ and enhanced expression of the Hippo signaling downstream genes CTGF and the pluripotency associated markers, including CD133, SOX2, Nanog, MYC and BMI1, leading to promotion of glioblastoma stem cell phenotype. Conversely, inhibition of miR-130b attenuated these effects. These findings provide a novel mechanism for Hippo signaling inactivation in cancer, indicating not only a potentially pivotal role for miR-130b in the progression of glioblastoma, but also may represent a new therapeutic target., (Copyright © 2015. Published by Elsevier Inc.)

The purpose of this study was to determine the impact of early (⩽6 months old), midterm (6-12 months old) and late (>12 months old) endoscopic third ventriculostomy (ETV) on the operative success rate and postoperative neurodevelopmental outcome of children with congenital obstructive hydrocephalus. We divided 63 children into three groups according to whether they underwent early, midterm or late ETV. Their preoperative developmental quotient (DQ) was assessed using the Gesell developmental diagnosis schedule (GDDS). Three and 6months after the initial procedure, GDDS was used to obtain postoperative DQ from two assessments (blinded and non-blinded). Meanwhile, two observers studied the operative success rate of initial ETV. There were no substantial differences between blinded and non-blinded assessments. The success rate of early ETV was only 20.8%. By contrast, this rate was 55% and 73.7% for midterm and late ETV, respectively. Before operation, we observed severe developmental abnormalities in all children (DQ score<40). However, children in midterm and late ETV groups achieved improvement after the operation, which was particularly remarkable in late ETV group. Six months after the first surgery, 16 (84.2%) children in the late ETV group, nine (45%) in the midterm ETV group and four (16.7%) in the early ETV group had moderate developmental disability. Nevertheless, overall prognosis for the three groups was not optimistic. There were no children with mild neurodevelopmental disability or normal function. Our data confirmed that age is a determinant for ETV effectiveness and overall prognosis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We retrospectively analysed routinely collected baseline data of 2252 patients with HIV infection registered in the National Free Antiretroviral Treatment Program in Xinjiang province, China, from 2006 to 2011 to estimate the prevalence and predictors of anaemia at the initiation of combined antiretroviral therapy. Anaemia was diagnosed using the criteria set forth by the World Health Organisation, and univariate and multivariate logistic regression analyses were performed to determine its predictors. The prevalences of mild, moderate, and severe anaemia at the initiation of combined antiretroviral therapy were 19.2%, 17.1%, and 2.6%, respectively. Overall, 38.9% of the patients were anaemic at the initiation of combined antiretroviral therapy. The multivariate logistic regression analysis indicated that Uyghur ethnicity, female gender, lower CD4 count, lower body mass index value, self-reported tuberculosis infection, and oral candidiasis were associated with a higher prevalence of anaemia, whereas higher serum alanine aminotransferase level was associated with a lower prevalence of anaemia. The results suggest that the overall prevalence of anaemia at the initiation of combined antiretroviral therapy in patients with HIV infection is high in Xinjiang, China, but severe anaemia is uncommon. Patients in China should be routinely checked for anaemia prior to combined antiretroviral therapy initiation, and healthcare providers should carefully select the appropriate first-line combined antiretroviral therapy regimens for anaemic patients., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Diffuse large B cell lymphoma (DLBCL) cells can be sub-classified into germinal center B cells (GCB) and non-GCB immunophenotypes. In the present study, we treated 161 newly diagnosed DLBCL patients with cyclophosphamide, epirubicin, vincristine, and prednisolone (CEOP) regimen with or without rituximab, and retrospectively investigated DLBCL sub-classifications combined with assessment of B cell lymphoma 2 (Bcl-2) expression level for their utility in the prediction of clinical efficacy. Survival analyses showed that non-GCB patients treated with R-CEOP regimen had significantly higher 5-year OS rates than the CEOP group (P = 0.033), while no statistically significant difference was observed between R-CEOP and CEOP treatments in GCB patients (P = 0.317). Prognosis was poorest for high Bcl-2 expressing non-GCB subgroup patients treated with CEOP, compared with Bcl-2 negative non-GCB CEOP patients (P = 0.044). In the R-CEOP group, Bcl-2 expression had no significant effect on prognosis for both GCB and non-GCB patients. The addition of rituximab to CEOP chemotherapy negates the adverse prognostic influence of Bcl-2 protein expression on overall survival in non-GCB DLBCL.

The aim of this study was to investigate the changes in serum pituitary hormone levels and the mechanism of hyponatremia in aneurysmal subarachnoid hemorrhage (SAH). Nuclear medical tests and serum electrolyte monitoring were performed in 49 aneurysmal SAH cases and 10 healthy volunteers. The levels of serum pituitary hormones were significantly higher in the SAH patients compared with the control group on days 1-3 and 7-9 after SAH onset (P<0.05). The peak value occurred on days 7-9. The rate of hyponatremia was 49.0% in the 49 SAH patients. The incidence of severe hyponatremia was significantly higher in Fisher grades III-IV and Hunt-Hess grades III-IV compared with Fisher grades I-II and Hunt-Hess grades I-II, respectively (P<0.05). There was no correlation between the site of aneurysm and the rate of hyponatremia. The incidence of symptomatic cerebral vasospasm was significantly higher in the hyponatremia group and Fisher grades III-IV compared with the normal serum sodium group and Fisher grades I-II, respectively. Serum pituitary hormone levels were positively correlated with blood loss and disease severity in patients with aneurysmal SAH. Hyponatremia may be considered an important indicator of SAH. SAH patients are likely to benefit from intense monitoring and regulation of serum sodium.

Objective: To evaluate methodological and reporting quality of the randomized controlled trials on cognitive-behavioral therapy(CBT) on temporomandibular disorders(TMD)., Methods: The electronic databases of Medline via Ovid, EMBASE, Cochrane Central Register of Controlled Trial, CBM and CNKI, and five Chinese stomatological journals were included to collect randomized controlled trial(RCT) and quasi-RCT(qRCT) on CBT on TMD. Data were assessed using the quality assessment criteria recommended by the Cochrane Collaboration, and the reporting quality was assessed using the consolidated standards of reporting trials (CONSORT) checklist., Results: 232 articles were collected by the search strategy, of which 5 (3 RCTs and 2 qRCTs) met the inclusion criteria. The methodological quality varied among the studies with 2 scored as B and 3 as C. The highest score evaluated by the CONSORT checklist was 24., Conclusion: The methodological qualities of included studies on CBT on TMD are generally low, and its reporting quality which is checked by CONSORT is also unsatisfactory yet.

Purpose: To analyze the clinical manifestations, radiological features, and surgical outcomes in 30 pediatric intracranial hydatid cysts., Methods: We reviewed the clinical, radiological, and surgical aspects of pediatric intracranial hydatid cysts patients who received surgical treatment at the Neurosurgical department of Xinjiang Medical University between the years 1985 to 2007, retrospectively., Results: Headache and vomiting were the most common initial symptoms in our series. Neurological deficits from the mass effect of the cysts were seen in 15 cases, including hemiparesis, visual deficit, and diplopia. Epilepsy occurred only in one patient with temporal lobe hydatid cyst. On computed tomography (CT), it presented as a round-shaped and thin-walled homogeneous low-density cystic lesion without surrounding edema and enhancement. Only five patients had a magnetic resonance imaging (MRI) scan, and presented low signal intensity on T1-weighted image and high signal intensity on T2-weighted image. Surgical removal of cyst was performed in all cases and intact removal was done in 29 cases. However, one cyst ruptured during the dissection of cyst wall, thus, resulting in one death. There were no additional neurological deficits which were caused directly by surgery., Conclusion: Increased intracranial pressure is common in patients with cerebral hydatid disease. CT and MRI are the first-line diagnostic procedures. Surgery is the treatment of choice for the majority of intracranial hydatid cysts. Multiple and deep seated lesions should receive medical treatment postoperatively.