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RATIONALE AND OBJECTIVES This study aimed to evaluate the value of background parenchymal enhancement (BPE) and diffusion-weighted image (DWI) histogram features in differentiating among different molecular subtypes of breast cancers and investigate the relationship between BPE and DWI features. MATERIALS AND METHODS We prospectively enrolled 142 patients with breast cancer between January and November 2018. All patients underwent breast magnetic resonance imaging before core needle biopsy. The quantitative BPE from dynamic enhanced images and the first-order histogram features extracted from DWI were analyzed. Univariate analysis of variance was used to compare differences in DWI histogram features and BPE characteristics among different molecular subtypes. Spearman test was used to compare the correlation between these imaging indexes. RESULTS A total of 142 patients had 142 lesions, including 17 cases of triple-negative breast cancer, 12 cases of luminal A type breast cancer, 39 cases of luminal B type breast cancer, and 74 cases of human epidermal growth factor receptor 2-positive breast cancer. The apparent diffusion coefficient (ADC) 95th percentile, ADC kurtosis, and BPE were significantly different among 4 subtype groups (P < 0.05), especially between the triple-negative subtype and any other subtype (P < 0.05 in pairwise comparisons). There was a weak but significant correlation between BPE and kurtosis of ADC (r = -0.176, P = 0.036). CONCLUSIONS Diffusion-weighted image histogram features (95th percentile ADC value and kurtosis value of ADC) and BPE features were different in the 4 molecular subtypes of breast cancer, especially in the triple-negative breast cancer subtype. Background parenchymal enhancement was negatively correlated with the kurtosis value of ADC.

Programmed cell death 10 (PDCD10) was initially considered as a protein associated with apoptosis. However, recent studies showed that PDCD10 is actually an adaptor protein. By interacting with multiple molecules, PDCD10 participates in various physiological processes, such as cell survival, migration, cell differentiation, vesicle trafficking, cellular senescence, neurovascular development, and gonadogenesis. Moreover, over the past few decades, accumulating evidence has demonstrated that the aberrant expression or mutation of PDCD10 is extremely common in various pathological processes, especially in cancers. The dysfunction of PDCD10 has been strongly implicated in oncogenesis and tumor progression. However, the updated data seem to indicate that PDCD10 has a dual role (either pro- or anti-tumor effects) in various cancer types, depending on cell/tissue specificity with different cellular interactors. In this review, we aimed to summarize the knowledge of the dual role of PDCD10 in cancers with a special focus on its cellular function and potential molecular mechanism. With these efforts, we hoped to provide new insight into the future development and application of PDCD10 as a clinical therapeutic target in cancers.

The optimal dose of galcanezumab for patients with migraine remains uncertain. Therefore, we conducted a network meta-analysis to assess the comparative effectiveness of various doses of galcanezumab for this group of patients.A systematically search was implemented in several databases including the PubMed, Ovid MEDILNE, Ovid EMBASE and Cochrane Library from inception of the databases until 31 August 2020. Only randomized clinical trials of adults with migraine that assessed galcanezumab therapy and reported clinical outcomes were included. The primary efficacy outcome was monthly change in migraine headache days (MHDs). The primary safety outcome was treatment-emergent adverse events (TEAEs).Overall, eight randomized clinical trials included 4,720 patients, were assessed in our systematic review. In terms of efficacy, galcanezumab 120 and 240 mg significantly reduced monthly MHDs (MD -2.02, 95% CrI -2.62 to -1.42; MD -2.06, 95% CrI -2.74 to -1.36, respectively) compared to the placebo. In terms of safety, galcanezumab 120, 150 mg and 240 mg significantly increased incidences of adverse events (RR 1.11, 95% CrI 1.03-1.20; RR 1.85, 95% CrI 1.27-2.81; RR 1.15, 95% CrI 1.06-1.24, respectively).Galcanezumab 240 mg offers the first level in terms of efficacy outcomes and galcanezumab 150 mg ranks the first level in terms of increasing treatment-emergent adverse events among adult patients with migraine. Attention should be devoted to the potential risk of adverse events, especially for injection site pain when the drug is administered subcutaneously.

Objective. To investigate the effect of microRNA-8126 (miR-8126) on isoflurane-induced hippocampal neurotoxicity in rats. Methods. A rat isoflurane nerve injury model was constructed. The expression of miR-8126 in the hippocampal region of normal and injured rats was measured by qRT-PCR; synaptic density protein-95, PAK-3 (p21-activated kinase-3) and apoptosis-related proteins cytochrome C, cleaved caspase-3, and cleaved PARP were detected by Western blot. The Cytochrome C, cleaved-caspase-3, and cleaved PARP expression was detected by WB, as well as GSH-Px, CAT, SOD, and ROS. Results. miR-8126 was lowly expressed in the isoflurane-treated rat hippocampal region and in rat hippocampal neuronal cells, and the expression of apoptosis-related proteins and apoptosis levels were significantly increased, and neural activity, cell activity, and proliferation capacity were significantly decreased. Oxidative stress levels and ROS content were significantly increased; overexpression of miR-8126 in the rat hippocampal region significantly inhibited oxidative stress and apoptosis. Overexpression of miR-8126 in rat hippocampal neural progenitor cells significantly increased cell activity, proliferative capacity, and significantly smaller mitochondrial size and it decreased ROS content and oxidative stress levels and apoptosis-related protein expression compared to isoflurane-treated cells; while inhibition of miR-8126 expression in rat hippocampal neuronal cells significantly decreased cell activity, proliferative capacity, and mitochondrial size compared to the control group. In contrast, inhibition of miR-8126 expression in rat hippocampal neuronal cells resulted in a further decrease in cell activity, proliferation capacity, and significantly larger mitochondrial size and increased expression of apoptosis-related proteins compared with the control group. miR-8126 regulates the activity of rat hippocampal neuronal cells by targeting ATF4. Conclusions. miR-8126 attenuates isoflurane-induced hippocampal neurotoxicity in rats by mediating antioxidative stress.

Until now, it has remained difficult for doctors to make an informative decision as to which concentration of hypertonic saline (HTS) is more beneficial for patients with traumatic brain injury (TBI). We therefore investigate the effect of different concentrations of hypertonic saline on mortality and ICP lowering efficacy in this group of patients.Several databases including Ovid MEDLINE, Ovid EMBASE, PubMed, and Cochrane Central Register of Controlled Trials were searched comprehensively from inception to February 28, 2022. We only included RCTs that compared HTS with different concentrations and mannitol in adult patients with TBI. The main outcome was mortality from any cause. We reported relative risks (RR) and 95% confidence intervals (CIs) from direct meta-analysis and 95% credible intervals (CrIs) from network meta-analysis.Overall, 13 trials containing 593 patients were included in this study. Direct analysis revealed that HTS was associated with decreased risk of all-cause mortality (RR, 1.29; 95% CI: 1.08 to 1.54). In the network meta-analysis, 5% HTS was associated with a significant decrease in all-cause mortality compared with mannitol (RR 0.34, 95% CrI: 0.14 to 0.72). We also found 7.5% HTS was associated with a significant increase in all-cause mortality compared with 5% HTS (RR, 2.87; 95% CrI: 1.00 to 8.99).Among patients with TBI, the application of 5% HTS was associated with decreased all-cause mortality compared with mannitol and other concentration. Treatments with 10% and 15% HTS was more likely to decrease ICP compared with other fluids. More trials are needed to verify the current findings.

Treating blood blister-like aneurysms (BBA) is a major neurosurgical challenge. Whether endovascular repair serves as a better strategy than microsurgery remains controversial. We aim to perform a propensity score-matched (PSM) retrospective study to analyze the short-term outcome in BBA patients who received microsurgery and endovascular treatment. One hundred fifty-five eligible patients with internal carotid artery BBA were retrospectively collected with demographic and angiographic baseline in a single center. Three-month outcome and adverse events were set as outcome endpoints. PSM was used to match the microsurgery and endovascular group. Matching effect was evaluated by distribution variation analysis and love plot. The outcome of neurosurgery and endovascular treatment was then compared before and after PSM. Better WFNS levels (p = .017) and modified Fisher grade (p = .027) were noted in endovascular group before matching. Other baseline including angiographic features were comparable between two groups. Before matching, the 3-month outcome of endovascular repair surgery was more favorable than microsurgery (p .0001). The occurrence of adverse events was also higher in the microsurgery group (p = .0079). In PSM-adjusted groups, the superior outcome effect of endovascular treatment still existed but with a reduced significance (p = .004). Similar trend was also observed in the adverse event rate (p = .038). Fatality rate was comparable between two adjusted groups regardless of PSM adjustment. Endovascular surgery of BBAs exhibits overall more favorable short-term outcome regardless of PSM matching. Microsurgery does not cause a higher fatality rate, hence it could be considered a salvage plan for those high-grade BBA patients.

Liu Zi,1,2,* Wencheng Zhou,1,3,* Jiake Xu,1,4 Junshu Li,5 Ning Li,2 Jianguo Xu,1,4,6 Chao You,1,4,6 Chengwei Wang,1,2 Meng Tian1,4,6 1Neurosurgery Research Laboratory, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Integrated Traditional and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People’s Republic of China; 6West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chengwei Wang; Meng TianNeurosurgery Research Laboratory, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of ChinaTel/Fax +86 28 85164168Email 21270526@qq.com; tianmong007@gmail.comBackground: Intracerebral hemorrhage (ICH), a devastating subtype of stroke, has a poor prognosis. However, there is no effective therapy currently available due to its complex pathological progression, in which neuroinflammation plays a pivotal role in secondary brain injury. In this work, the use of statin-loaded nanomicelles to target the neuroinflammation and improve the efficacy was studied in a mouse model of ICH.Methods: Rosuvastatin-loaded nanomicelles were prepared by a co-solvent evaporation method using polyethylene glycol-poly(ϵ-caprolactone) (PEG-PCL) copolymer as a carrier. The prepared nanomicelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), and then in vitro and in vivo studies were performed.Results: TEM shows that the nanomicelles are spherical with a diameter of about 19.41 nm, and DLS shows that the size, zeta potential, and polymer dispersity index of the nanomicelles were 23.37 nm, − 19.2 mV, and 0.221, respectively. The drug loading content is 8.28%. The in vivo study showed that the nanomicelles significantly reduced neuron degeneration, inhibited the inflammatory cell infiltration, reduced the brain edema, and improved neurological deficit. Furthermore, it was observed that the nanomicelles promoted the polarization of microglia/macrophages to M2 phenotype, and also the expression of the proinflammatory cytokines, such as IL-1β and TNF-α, was significantly down-regulated, while the expression of the anti-inflammatory cytokine IL-10 was significantly up-regulated. The related mechanism was proposed and discussed.Conclusion: The nanomicelles treatment suppressed the neuroinflammation that might contribute to the promoted nerve functional recovery of the ICH mouse, making it potential to be applied in clinic.Keywords: rosuvastatin, nanomicelles, neuroinflammation, intracerebral hemorrhage

Expanding urbanization and agricultural intensification across neighboring South Asia and East Asia have substantially threatened atmospheric condition over the Third Pole (TP) during the past few decades. Whether the atmospheric condition over the TP is still as clean as a representative of the regional background draws great concern. In this work, great differences in levoglucosan concentration within/above the atmospheric boundary layer height are revealed. Levoglucosan results support the hypothesis that atmospheric pollutants in the mid-troposphere over the TP are mainly affected by long-range transport, although there are some local biomass burning emissions in residential areas. In addition, levoglucosan concentration in the mid-troposphere over the TP is at the same magnitude as marine and polar regions, but about 2–3 magnitudes lower than neighboring densely-populated Asian regions. With insights of levoglucosan records, this work therefore proves that the high-altitude TP still has largely pristine atmospheric conditions, and is one of the cleanest remote regions on the Earth.

With the continuous implementation of the carbon peak and carbon neutrality, a large number of distributed solar power stations have been integrated into the grid, which has caused a strong impact on the safe and stable operation of the traditional power system. Based on this, the grid-connected mode of distributed solar power stations is studied, and three types of grid connection are proposed. Mode A is merged into the 66 kV bus side of the 220 kV substation through the 66 kV dedicated line; Mode B is merged into the 66 kV bus side of the 66 kV substation through the 66 kV dedicated line; Mode C is T-connected to the 66 kV transmission line through 66 kV dedicated line. By using a power system analysis software package (PSASP), we can build a model of a certain regional power grid and study the effects of the above three grid-connected modes on system voltage stability, short-circuit current, and network loss. The study shows that the three modes are all feasible. Mode A has the smallest change in voltage quality and short-circuit current of the grid-connected substation and has the smallest network loss of the three modes.

Intracerebral hemorrhage (ICH) will be accompanied by the overload of iron and reactive oxygen species (ROS) following hematoma clearance. Although deferoxamine (DFO) has been widely utilized as a clinical first-line siderophore to remove the iron overload, the ROS-inducing damage still greatly limits the therapeutic effect of DFO. To address this issue, we designed and fabricated a series of dual-functional macromolecular nanoscavengers featuring high-density DFO units and catechol moieties. Note that the former units could effectively remove the iron overload, while the latter ones could efficiently deplete the ROS. The resulting nanoscavengers efficiently down-regulate the iron and ROS levels as well as significantly reduce the cell death in both iron-overloaded RAW 264.7 cells and the ICH mice model. This work suggests a novel clue for the ICH-ameliorated iron-depleting interventional therapeutic regimen.

ObjectiveStroke is a leading cause of death and disability worldwide. Neuroprotective approaches have failed in clinical trials, thus warranting therapeutic innovations with alternative targets. The gut microbiota is an important contributor to many risk factors for stroke. However, the bidirectional interactions between stroke and gut microbiota remain largely unknown.DesignWe performed two clinical cohort studies to capture the gut dysbiosis dynamics after stroke and their relationship with stroke prognosis. Then, we used a middle cerebral artery occlusion model to explore gut dysbiosis post-stroke in mice and address the causative relationship between acute ischaemic stroke and gut dysbiosis. Finally, we tested whether aminoguanidine, superoxide dismutase and tungstate can alleviate post-stroke brain infarction by restoring gut dysbiosis.ResultsBrain ischaemia rapidly induced intestinal ischaemia and produced excessive nitrate through free radical reactions, resulting in gut dysbiosis with Enterobacteriaceae expansion. Enterobacteriaceae enrichment exacerbated brain infarction by enhancing systemic inflammation and is an independent risk factor for the primary poor outcome of patients with stroke. Administering aminoguanidine or superoxide dismutase to diminish nitrate generation or administering tungstate to inhibit nitrate respiration all resulted in suppressed Enterobacteriaceae overgrowth, reduced systemic inflammation and alleviated brain infarction. These effects were gut microbiome dependent and indicated the translational value of the brain–gut axis in stroke treatment.ConclusionsThis study reveals a reciprocal relationship between stroke and gut dysbiosis. Ischaemic stroke rapidly triggers gut microbiome dysbiosis with Enterobacteriaceae overgrowth that in turn exacerbates brain infarction.

Many blood blister aneurysms (BBAs) have been documented with a rapid progression history in repeated angiography. The underlying mechanism and clinical significance remained elusive. This current study aims to clarify the clinical and histopathological differences between short-term progressive BBA and non-progressive BBAs. Eighty-one patients with BBAs were consecutively included for this single-center retrospective analysis. Clinical and radiological data on these patients were retrieved from 2017 to 2019. BBAs were defined as either progressive or non-progressive based on observed growth based on repeated imaging. Histopathological examinations of a saccular aneurysm, a progressive BBA, and a non-progressive BBA were conducted using representative aneurysm samples. Among all enrolled patients, 26 of the them were identified with progressive BBAs, while the other 55 with non-progressive BBAs. Progressive BBAs were diagnosed significantly earlier in angiography (3.36 ± 0.61 vs. 6.53 ± 1.31 days, p < 0.05) and showed a higher presence rate of daughter sacs (61.5 vs. 38.2%, p < 0.05). Three different progression patterns were identified. BBAs that developed daughter sac enlargement are diagnosed significantly later than BBAs exhibiting other progression patterns. Patients with progressive and non-progressive BBAs exhibited similar overall clinical outcomes and incidence for complications. For patients with non-progressive BBAs, microsurgery appears to be inferior to endovascular treatment, while for patients with progressive BBAs, the short-term outcomes between microsurgery and endovascular treatment were identical. Histopathological analysis revealed that both subtypes shared a similar pseudoaneurysms structure, but non-progressive BBAs had more histologically destructed aneurysm wall with less remnant fibrillar collagen in adventitia. Progressive and non-progressive BBAs may not be distinct pathological lesions but represent different stages during the BBA development. Early intervention, regardless of treatment methods, is recommended for salvageable patients with progressive BBAs, but microsurgery should be performed with caution for non-progressive BBAs due to increased surgical risk.

The use of prophylactic anticonvulsants among patients with subarachnoid hemorrhage (SAH) is controversial. We sought to assess the effectiveness of different durations of prophylactic antiepileptic drug (AED) use among SAH patients. We searched the MEDLINE, Embase, Cochrane, and ClinicalTrials.gov databases until March 1, 2020. Randomized controlled trials or observational studies comparing different durations or different drugs were selected. The primary outcome was poor clinical outcomes. The secondary outcome was in-hospital seizure. Bayesian network meta-analysis was also performed to indirectly compare the effectiveness of different prophylaxes. A total of 5 papers were included. Three studies with a total of 959 patients were included in the analysis of the primary outcome; the results showed that long-term exposure to prophylactic AEDs (more than 3 days) led to poor clinical outcomes (OR 1.55; 95% CI 1.01–2.39; p = 0.045). Four studies with 1024 patients were included in the analysis of the secondary outcome; the results showed no association between the duration of prophylactic AED use and the occurrence of in-hospital seizures (OR 0.62; 95% CI 0.18–2.15; p = 0.447). In the network meta-analysis, no significant difference was found among the four different prophylaxes. Our findings suggested that, when compared with the short-term use, the long-term use of prophylactic AEDs in SAH patients has a similar effect on in-hospital seizure prevention but is associated with poor clinical outcomes. However, these findings were based on a small number of available studies with obvious heterogeneity in study design and different prescription regimens. Further well-designed studies are warranted to elucidate these questions.

Lijuan Shen,1,2,* Xiaowen Ma,2,3,* Tingting Jiang,2,3 Xigang Shen,2,3 Wentao Yang,3,4 Chao You,2,3 Weijun Peng2,3 1Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China; 2Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 3Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 4Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weijun Peng; Chao YouFudan University Shanghai Cancer Center, No. 270, Dongan Road, Xuhui District, Shanghai 200032, People’s Republic of ChinaTel +86-15026544096; +86-21-64175590Fax +86-21-64174774Email cjr.pengweijun@vip.163.com : youchao8888@aliyun.comPurpose: To explore the potential factors influencing the malignancy risk of amorphous calcifications and establish a predictive nomogram for malignancy risk stratification.Patients and Methods: Consecutive mammograms from January 2013 to December 2018 were retrospectively reviewed. Traditional clinical features were recorded, and mammographic features were estimated according to the 5th BI-RADS. Included calcifications were randomly divided into the training and validation cohorts. A nomogram was developed to graphically predict the risk of malignancy (risk) based on stepwise multivariate logistic regression analysis. The discrimination and calibration performance of the model were assessed in both the training and validation cohorts.Results: Finally, 1018 amorphous calcifications with final pathological results in 907 women were identified with a malignancy rate of 28.4% (95% CI: 25.7%, 31.3%). The malignancy rates of subgroups divided by the distribution of calcifications, quantity of calcifications, age, menopausal status and family history of cancer were significantly different. There were 712 cases and 306 cases in the training and validation cohorts. The prediction nomogram was finally developed based on four risk factors, including age and distribution, maximum diameter and quantity of calcifications. The AUC of the nomogram was 0.799 (95% CI: 0.761, 0.836) in the training cohort and 0.795 (95% CI: 0.738, 0.852) in the validation cohort.Conclusion: On mammography, the distribution, maximum diameter and quantity of calcifications are independent predictors of malignant amorphous calcifications and can be easily obtained in the clinic. The nomogram developed in this study for individualized malignancy risk stratification of amorphous calcifications shows good discrimination performance.Keywords: breast cancer, mammography, calcifications, malignancy risk stratification, nomogram

Bo Wang,1,2 Yang Li,3 Chao You1 1Department of Neurosurgery, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China; 2Department of Neurosurgery, Kunming Medical University First Affiliated Hospital, Kunming, Yunnan 650032, People’s Republic of China; 3Intensive Care Unit, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People’s Republic of ChinaCorrespondence: Chao YouDepartment of Neurosurgery, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People’s Republic of ChinaTel +86 28-85422026Email youchaohuaxi@126.comIntroduction: Glucose fluctuations have an adverse effect on several diabetes-related complications, especially for the nervous system, but the underlying mechanisms are not clear. MicroRNAs are critical regulators of posttranscription in many physiological processes, such as apoptosis. Our study clarified the neuroprotective effects of miR-129-3p targeting mitochondrial calcium uniporter (MCU) in glucose fluctuation-mediated neuronal damage and the specific mechanisms involved.Methods: The expression of MCU and miR-129-3p was examined by real-time PCR and Western blot in the glucose fluctuation cell model. Dual-luciferase reporter assay was performed to confirm the transcriptional regulation of miR-129-3p by MCU. Fluorescent probe and assay kit assay was used to determine oxidative stress condition. Mitochondrial-dependent intrinsic apoptotic factors were examined by flow cytometry assay, enzyme-linked immunosorbent assay (ELISA), and gene and protein expression assays.Results: We found an upregulation of MCU and downregulation of miR-129-3p in glucose fluctuation-treated primary hippocampal neuronal cells, and miR-129-3p directly targeted MCU. miR-129-3p overexpression produced a dramatic reduction in calcium overload, reactive oxygen species (ROS) generation, GSH-to-GSSG ratio, MMP-2 expression in the mitochondrial-dependent intrinsic apoptosis pathway and an increase in MnSOD activity. Increasing MCU expression rescued the effects of miR-129-3p overexpression. miR-129-3p downregulation produced a significant increase in calcium overload, reactive oxygen species (ROS) generation, MMP-2 expression, cytochrome c release and cell apoptosis, and antioxidant N-acetyl cysteine (NAC) rescued the effects of miR-129-3p downregulation.Conclusion: Therefore, miR-129-3p suppressed glucose fluctuation-mediated neuronal damage by targeting MCU via a mitochondrial-dependent intrinsic apoptotic pathway. The miR-129-3p/MCU axis may be a promising therapeutic target for glucose fluctuation-mediated neuronal damage.Keywords: miR-129-3p, MCU, calcium, ROS, mitochondrion, apoptosis, oxidative stress

OBJECTIVE Hyperglycemia is associated with worse outcomes in ambulatory settings and specialized hospital settings, but there are sparse data on the importance of preoperative blood glucose measurement before brain tumor craniotomy. The authors sought to investigate the association between preoperative glucose level and 30-day mortality rate in patients undergoing brain tumor resection. METHODS This retrospective cohort study included patients undergoing craniotomy for brain tumors at West China Hospital, Sichuan University, from January 2011 to March 2021. Surgical mortality rates were evaluated in patients who had normal glycemia (< 5.6 mmol/L) as well as mild (5.6–6.9 mmol/L), moderate (7.0–11.0 mmol/L), and severe hyperglycemia (> 11.0 mmol/L). RESULTS The study included 12,281 patients who underwent tumor resection via craniotomy. The overall 30-day mortality rate was 2.0% (242/12,281), whereas the rates for normal glycemia and mild, moderate, and severe hyperglycemia were 1.5%, 2.5%, 3.8%, and 6.5%, respectively. Compared with normal glycemia, the odds of mortality at 30 days were higher in patients with mild hyperglycemia (adjusted odds ratio [OR] 1.44, 95% confidence interval [CI] 1.05–2.00), moderate hyperglycemia (OR 2.04, 95% CI 1.41–2.96), and severe hyperglycemia (OR 3.76, 95% CI 1.96–7.20; p < 0.001 for trend). When blood glucose was analyzed as a continuous variable, for each 1 mmol/L increase in blood glucose, the adjusted OR of 30-day mortality was 1.13 (95% CI 1.08–1.19). The addition of a preoperative glucose level significantly improved the area under the curve and categorical net reclassification index for prediction of mortality. CONCLUSIONS In patients undergoing craniotomy for brain tumors, even mild hyperglycemia was associated with an increased mortality rate, at a glucose level that was much lower than the commonly applied level.

IntroductionSeizures are a common complication that leads to neurological deficits and affects outcomes after aneurysmal subarachnoid haemorrhage (aSAH). However, whether to use prophylactic anticonvulsants in patients with aSAH remains controversial. Our study aims to determine whether short-term (7 days) sodium valproate could prevent seizure occurrence and improve neurological function in patients with SAH caused by anterior circulation aneurysm rupture and treated with clipping.Methods and analysisIn this multicentre randomised evaluator-blind placebo-controlled trial, 182 eligible patients with good-grade aSAH planned for surgical clipping will be enrolled from four neurosurgical centres in China. In addition to standard care, patients will be randomly assigned to receive sodium valproate 20 mg/kg daily or matching placebo. After aneurysmal clipping, patients will be followed up at discharge, 90 days and 180 days. The primary outcomes are the incidence of early and late seizures. The secondary outcomes include aSAH-related complications, sodium valproate-related adverse effects, modified Rankin Scale (mRS) (on discharge, at 90 days, 180 days), rate of good outcome (defined as mRS 0–2), all-cause death (at 90 days, 180 days) and Montreal Cognitive Assessment score (at 180 days). All analyses are by intention-to-treat.Ethics and disseminationThis study will be conducted according to the principles of Declaration of Helsinki and good clinical practice guidelines. This trial involves human participants and has been approved by the ethics committee of West China Hospital. Informed consent will be achieved from each included patient and/or their legally authorised representative. Preliminary and final results from this study will be disseminated through manuscript publishing and international congresses presentations. Any protocol amendments will be approved by the ethics committee of West China Hospital and subsequently updated on ChiCTR.Trial registration numberChiCTR.org identifier: ChiCTR2100050161.

OBJECTIVE: Interleukin 6 (IL-6) is an inflammatory cytokine released into the periphery after stroke, involved in the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to explore the relationship between serum IL-6 with long-term mortality after aSAH.METHODS: We retrospectively reviewed the medical records of 18824 SAH patients for collection of serum IL-6 levels during hospitalization from a large, single-center aSAH database of Sichuan University West China Hospital. Patient deaths were determined through a national death record registration system. The primary outcome was long-term mortality. Cox regression models were used to investigate univariate and multivariate relationships between predictors and outcomes. A propensity score-matched analysis was conducted to minimize bias from confounding variables.RESULTS: In total, we included 1131 aSAH patients with 3288 records of IL-6 collections. Initial serum IL-6 values were elevated in all, ranging from 1.50 to 4522.00 pg/ml. After logarithmic transformation, the IL-6 was associated with long-term mortality (HR 1.32, 95% CI 1.21-1.44). The results maintained significant in the multivariate cox regression and propensity score-matched analysis (adjusted HR 1.23, 95% CI 1.11-1.36, p103.00 pg/ml vs IL-6≤103. 00 pg/ml, PSM HR 1.94, 95% CI 1.48-2.55, pCONCLUSIONS: Serum IL-6 is independently associated with long-term mortality of aSAH patients. Our study provided new evidence for the investigation of inflammation after aSAH and the association of inflammatory cytokines with the long-term prognosis of aSAH and might support future management decisions.

New found in biochemical characteristics of placenta can bring new insight for further studies on the possible markers of physiological/pathological pregnancy or function of placenta. We compared the proteome of dairy cow placenta enzymatic hydrolysis by different proteases by label-free mass spectrometry approach. In total 541, 136 and 86 proteins were identified in trypsin group (TRY), pepsin group (PEP) and papain group (PAP). By comparing the proteome of PAP and TRY, 432 differentially expressed proteins (DEPs) were identified. PEP vs TRY identified 421 DEPs, while 136 DEPs were identified in PEP and PAP. The results showed the proteins identified by papain are mostly derived from extracellular matrix and collagen and enriched in relaxin signaling pathway, AGE-RAGE signaling pathway in diabetic complications; pepsin digestion can identify more muscle-related proteins, which are enriched in lysosome, platelet activation, cardiac muscle contraction, bacterial invasion of epithelial cell and small cell lung cancer; trypsin mainly enzymatically degrades extracellular matrix, blood particles, and cell surface proteins which enriched in arginine and proline metabolism, olfactory transduction proteasome, protein processing in endoplasmic reticulum, pyruvate metabolism and arrhythmogenic right ventricular cardiomyopathy (ARVC). In summary, these results provide insights into the selection of protease in dairy cow placenta proteomics.

We aimed to investigate prognostic factors and outcomes of malignant meningioma and to construct a nomogram model of survival.Patients with malignant meningioma were collected from the Surveillance, Epidemiology, and End Results database. The nomogram was developed for the 3-, 5-, and 8-year prediction of overall survival (OS) and cancer-specific survival (CSS). Harrell's concordance index (C-index) and decision curve analysis (DCA) were used to verify the predicted effect of the nomogram.Between 1998 and 2016, 806 adult patients with histologically confirmed malignant meningioma were included. The mean age at diagnosis was 61.0 years (median 61.0 years), with a range of 19-104 years. Univariate analysis revealed that male gender, distant metastasis, and age ≥ 80 years as significant adverse factors for OS and CSS. These factors remained significance in the multivariate analysis. The nomogram demonstrated satisfactory discrimination, with a C-index value of 0.663 for OS and 0.654 for CSS, respectively. For both OS and CSS, the DCA curves indicated that the nomogram model performed better than other clinical variables.Older age, male gender, distant metastasis, and radiotherapy were significantly related to poor prognosis; and extent of resection did not affect survival.