Publications by authors named "Anke Zhang"

12 Publications

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Development of a nomogram for predicting clinical outcome in patients with angiogram-negative subarachnoid hemorrhage.

CNS Neurosci Ther 2021 Jul 28. Epub 2021 Jul 28.

Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China.

To the best of our knowledge, this is the largest clinical retrospective study in AN-SAH patients, and is the first time to establish accurate predictive models paired with bleeding pattern.

Background: Angiogram-negative subarachnoid hemorrhage (AN-SAH) has a definite incidence of delayed cerebral ischemia (DCI) and poor clinical outcomes. The purpose is to screen independent factors and establish a nomogram to guide the clinical therapy and assess post-discharge prognosis.

Methods: We identified 273 consecutive patients referred to our institute from 2013 to 2018 for AN-SAH. A nomogram to predict poor outcomes was formulated based on the multivariable models of independent risk factors. The accuracy and discrimination of nomograms were determined in training and internal validation cohorts.

Results: The overall poor outcome rates of AN-SAH were 14.3% and 8.7% at 3 months and 12 months, respectively. In addition, perimesencephalic AN-SAH (PAN-SAH) presented with a more unfavorable prognosis compared with non-perimesencephalic AN-SAH (NPAN-SAH). The clinical prognosis was associated with the World Federation of Neurosurgical Societies scale (WFNS) (odds ratio, 3.82 [95% CI, 1.15-12.67] for 3-month outcome; and odds ratio, 31.69 [95% CI, 3.65-275.43] for 12-month outcome), Subarachnoid hemorrhage Early Brain Edema Score (SEBES) (odds ratio, 10.39 [95% CI, 1.98-54.64] for 3-month outcome; odds ratio, 10.01 [95% CI, 1.87-53.73] for 12-month outcome), and symptomatic vasospasm (odds ratio, 3.16 [95% CI, 1.03-9.70] for 3-month outcome; odds ratio, 5.15 [95% CI, 1.34-19.85] for 12-month outcome). The nomogram was constructed based on the above features, which represented great predictive value in clinical outcomes.

Conclusions: Symptomatic vasospasm, high WFNS, cerebral edema, and NPAN-SAH after hemorrhage were associated with poor outcome of AN-SAH. The nomogram with WFNS (3-5), SEBES (3-4), vasospasm, and NPAN-SAH represented a practical approach to provide individualized risk assessment for AN-SAH patients.
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http://dx.doi.org/10.1111/cns.13712DOI Listing
July 2021

ITGB2 as a prognostic indicator and a predictive marker for immunotherapy in gliomas.

Cancer Immunol Immunother 2021 Jul 27. Epub 2021 Jul 27.

Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.

Purpose: Glioma is the most common primary tumor in the brain, accounting for 81% of intracranial malignancies. Nowadays, cancer immunotherapy has become a novel and revolutionary treatment for patients with advanced, highly aggressive tumors. However, to date, there are no effective biomarkers to reflect the response of glioma patients to immunotherapy. In this study, we aimed to assess the clinical predictive value of ITGB2 in patients with glioma.

Methods: The correlation between ITGB2 expression levels and glioma progression was explored and validated using data from CGGA, TCGA, GEO datasets, and patient samples from our hospital. Univariate and multivariate cox regression models were developed to determine the predictive role of ITGB2 on the prognosis of patients with glioma. The relationship between ITGB2 and immune activation was then analyzed. Finally, we predicted the immunotherapy response in both high and low ITGB2 expression subgroups.

Results: ITGB2 was significantly elevated in gliomas with higher malignancy and predicted poor prognosis. In multivariate analysis, the hazard ratio for ITGB2 expression (low versus high) was 0.71 with 95% CI (0.59-0.85) (P < 0.001). Furthermore, we found that ITGB2 stratified glioma patients into high and low ITGB2 expression subgroups, exhibiting different clinical outcomes and immune activation status. At last, we demonstrated that glioma patients with high ITGB2 expression levels had better immunotherapy response.

Conclusions: This study demonstrated ITGB2 as a novel predictor for clinical prognosis and response to immunotherapy in gliomas. Assessing expression levels of ITGB2 is a promising method to discover patients that may benefit from immunotherapy.
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http://dx.doi.org/10.1007/s00262-021-03022-2DOI Listing
July 2021

Establishment of a nomogram with EMP3 for predicting clinical outcomes in patients with glioma: A bi-center study.

CNS Neurosci Ther 2021 Oct 16;27(10):1238-1250. Epub 2021 Jul 16.

Department of Neurosurgery, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China.

Aim: To demonstrate the clinical value of epithelial membrane protein 3 (EMP3) with bioinformatic analysis and clinical data, and then to establish a practical nomogram predictive model with bicenter validation.

Methods: The data from CGGA and TCGA database were used to analyze the expression of EMP3 and its correlation with clinical prognosis. Then, we analyzed EMP3 expression in samples from 179 glioma patients from 2013 to 2017. Univariate and multivariate cox regression were used to predict the prognosis with multiple factors. Finally, a nomogram to predict poor outcomes was formulated. The accuracy and discrimination of nomograms were determined with ROC curve and calibration curve in training and validation cohorts.

Results: EMP3 was significantly higher in higher-grade glioma and predicted poor prognosis. In multivariate analysis, high expression of EMP3 (HR = 2.842, 95% CI 1.984-4.071), WHO grade (HR = 1.991, 95% CI 1.235-3.212), and IDH1 mutant (HR = 0.503, 95% CI 0.344-0.737) were included. The nomogram was constructed based on the above features, which represented great predictive value in clinical outcomes.

Conclusion: This study demonstrated EMP3 as a novel predictor for clinical progression and clinical outcomes in glioma. Moreover, the nomogram with EMP3 expression represented a practical approach to provide individualized risk assessment for glioma patients.
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http://dx.doi.org/10.1111/cns.13701DOI Listing
October 2021

Ferroptosis: An emerging therapeutic target in stroke.

J Neurochem 2021 Mar 18. Epub 2021 Mar 18.

Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Stroke is a disastrous neurological disease with high morbidity and mortality. The mechanism of the pathological process is extremely complicated and unclear. Although many basic studies have confirmed molecular mechanism of brain injury after stroke, these studies have not yet translated into treatment and clinical application. Ferroptosis is a form of cell death that is distinct from necrosis, apoptosis, and autophagy morphologically and biochemically and is characterized by iron-dependent accumulation of lipid peroxides. Despite ferroptosis being first identified in cancer cells, it was recently revealed to also be a significant factor in the pathological process of stroke. A better understanding of ferroptosis in stroke may provide us with better therapeutic targets to treat this devastating disease. Here, we systematically summarized the current mechanism of ferroptosis and reviewed the current studies regarding the relationship between ferroptosis and stroke.
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http://dx.doi.org/10.1111/jnc.15351DOI Listing
March 2021

Lactate-induced M2 polarization of tumor-associated macrophages promotes the invasion of pituitary adenoma by secreting CCL17.

Theranostics 2021 6;11(8):3839-3852. Epub 2021 Feb 6.

Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Lactate greatly contributes to the regulation of intracellular communication within the tumor microenvironment (TME). However, the role of lactate in pituitary adenoma (PA) invasion is unclear. In this study, we aimed to clarify the effects of lactate on the TME and the effects of TME on PA invasion. To explore the correlation between TME acidosis and tumor invasion, LDHA and LAMP2 expression levels were quantified in invasive (n = 32) and noninvasive (n = 32) PA samples. The correlation between immune cell infiltration and tumor invasion was evaluated in 64 PAs. Critical chemokine and key signaling pathway components were detected by qPCR, Western blotting, siRNA knockdown, and specific inhibitors. The functional consequences of CCR4 signaling inhibition were evaluated and . Lactate was positively associated with PA invasion. Of the 64 PA tissues, invasive PAs were related to high infiltration of M2-like tumor-associated macrophages (TAMs) (P < 0.05). Moreover, lactate secreted from PA cells facilitated M2 polarization the mTORC2 and ERK signaling pathways, while activated TAMs secreted CCL17 to promote PA invasion the CCL17/CCR4/mTORC1 axis. According to univariate analysis of clinical data, high CCL17 expression was associated with larger tumor size (P = 0.0438), greater invasion (P = 0.0334), and higher susceptibility to postoperative recurrence (P = 0.0195) in human PAs. This study illustrates the dynamics between PA cells and immune TME in promoting PA invasion M2 polarization. CCL17 levels in the TME are related to the PA invasiveness and clinical prognosis, and the CCL17/CCR4/mTOCR1 axis may serve as potential therapeutic targets for Pas.
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http://dx.doi.org/10.7150/thno.53749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914368PMC
July 2021

Prognostic and predictive value of FCER1G in glioma outcomes and response to immunotherapy.

Cancer Cell Int 2021 Feb 12;21(1):103. Epub 2021 Feb 12.

Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.

Purpose: Glioma is the most prevalent malignant form of brain tumors, with a dismal prognosis. Currently, cancer immunotherapy has emerged as a revolutionary treatment for patients with advanced highly aggressive therapy-resistant tumors. However, there is no effective biomarker to reflect the response to immunotherapy in glioma patient so far. So we aim to assess the clinical predictive value of FCER1G in patients with glioma.

Methods: The expression level and correlation between clinical prognosis and FER1G levels were analyzed with the data from CGGA, TCGA, and GEO database. Univariate and multivariate cox regression model was built to predict the prognosis of glioma patients with multiple factors. Then the correlation between FCER1G with immune cell infiltration and activation was analyzed. At last, we predict the immunotherapeutic response in both high and low FCER1G expression subgroups.

Results: FCER1G was significantly higher in glioma with greater malignancy and predicted poor prognosis. In multivariate analysis, the hazard ratio of FCER1G expression (Low versus High) was 0.66 and 95 % CI is 0.54 to 0.79 (P < 0.001), whereas age (HR = 1.26, 95 % CI  1.04-1.52), grade (HR = 2.75, 95 % CI 2.06-3.68), tumor recurrence (HR = 2.17, 95 % CI  1.81-2.62), IDH mutant (HR = 2.46, 95 % CI 1.97-3.01) and chemotherapeutic status (HR = 1.4, 95 % CI  1.20-1.80) are also included. Furthermore, we illustrated that gene FCER1G stratified glioma cases into high and low FCER1G expression subgroups that demonstrated with distinct clinical outcomes and T cell activation. At last, we demonstrated that high FCER1G levels presented great immunotherapeutic response in glioma patients.

Conclusions: This study demonstrated FCER1G as a novel predictor for clinical diagnosis, prognosis, and response to immunotherapy in glioma patient. Assess expression of FCER1G is a promising method to discover patients that may benefit from immunotherapy.
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http://dx.doi.org/10.1186/s12935-021-01804-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881595PMC
February 2021

Single-shot compressed ultrafast photography based on U-net network.

Opt Express 2020 Dec;28(26):39299-39310

The compressive ultrafast photography (CUP) has achieved real-time femtosecond imaging based on the compressive-sensing methods. However, the reconstruction performance usually suffers from artifacts brought by strong noise, aberration, and distortion, which prevents its applications. We propose a deep compressive ultrafast photography (DeepCUP) method. Various numerical simulations have been demonstrated on both the MNIST and UCF-101 datasets and compared with other state-of-the-art algorithms. The result shows that our DeepCUP has a superior performance in both PSNR and SSIM compared to previous compressed-sensing methods. We also illustrate the outstanding performance of the proposed method under system errors and noise in comparison to other methods.
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http://dx.doi.org/10.1364/OE.398083DOI Listing
December 2020

Prognosis Analysis and Validation of mA Signature and Tumor Immune Microenvironment in Glioma.

Front Oncol 2020 5;10:541401. Epub 2020 Oct 5.

Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Glioma is one of the most typical intracranial tumors, comprising about 80% of all brain malignancies. Several key molecular signatures have emerged as prognostic biomarkers, which indicate room for improvement in the current approach to glioma classification. In order to construct a more veracious prediction model and identify the potential prognosis-biomarker, we explore the differential expressed mA RNA methylation regulators in 665 gliomas from TCGA-GBM and TCGA-LGG. Consensus clustering was applied to the m6A RNA methylation regulators, and two glioma subgroups were identified with a poorer prognosis and a higher grade of WHO classification in cluster 1. The further chi-squared test indicated that the immune infiltration was significantly enriched in cluster 1, indicating a close relation between mA regulators and immune infiltration. In order to explore the potential biomarkers, the weighted gene co-expression network analysis (WGCNA), along with Least absolute shrinkage and selection operator (LASSO), between high/low immune infiltration and mA cluster 1/2 groups were utilized for the hub genes, and four genes ( were identified as prognostic biomarkers. Besides, a prognostic model was constructed based on the four genes with a good prediction and applicability for the overall survival (OS) of glioma patients (the area under the curve of ROC achieved 0.80 (0.76-0.83) and 0.72 (0.68-0.76) in TCGA and Chinese Glioma Genome Atlas (CGGA), respectively). Moreover, we also found and were highly expressed in high-grade glioma from The Human Protein Atlas database and both of them were correlated with m6A and immune cell marker in glioma tissue samples. In conclusion, we construct a novel prognostic model which provides new insights into glioma prognosis. The and may serve as potential biomarkers for prognosis of glioma.
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http://dx.doi.org/10.3389/fonc.2020.541401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571468PMC
October 2020

HCK promotes glioblastoma progression by TGFβ signaling.

Biosci Rep 2020 06;40(6)

Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, China.

The hematopoietic cell kinase (HCK), a member of the Src family protein-tyrosine kinases (SFKs), is primarily expressed in cells of the myeloid and B lymphocyte lineages. Nevertheless, the roles of HCK in glioblastoma (GBM) remain to be examined. Thus, we aimed to investigate the effects of HCK on GBM development both in vitro and in vivo, as well as the underlying mechanism. The present study found that HCK was highly expressed in both tumor tissues from patients with GBM and cancer cell lines. HCK enhanced cell viability, proliferation, and migration, and induced cell apoptosis in vitro. Tumor xenografts results also demonstrated that HCK knockdown significantly inhibited tumor growth. Interestingly, gene set enrichment analysis (GSEA) showed HCK was closed associated with epithelial mesenchymal transition (EMT) and TGFβ signaling in GBM. In addition, we also found that HCK accentuates TGFβ-induced EMT, suggesting silencing HCK inhibited EMT through the inactivation of Smad signaling pathway. In conclusion, our findings indicated that HCK is involved in GBM progression via mediating EMT process, and may be served as a promising therapeutic target for GBM.
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http://dx.doi.org/10.1042/BSR20200975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300285PMC
June 2020

Diabetes mellitus contributes to carbamazepine resistance in patient with trigeminal neuralgia.

Neurosurg Rev 2021 Apr 24;44(2):1119-1125. Epub 2020 Apr 24.

School of Medicine, Tongji University, Shanghai, China.

Objective: To determine whether diabetes mellitus (DM) contributes to the drug resistance of carbamazepine (CBZ), we investigated the correlation between the blood glucose status and the CBZ resistance condition in patients with trigeminal neuralgia (TN).

Patients And Methods: A total of 155 TN patients treated with the CBZ monotherapy were selected at Shanghai General Hospital and Shanghai Xinhua Hospital from September 2018 to January 2020. Among them, 15 were diagnosed with DM. Patients' CBZ resistance levels were evaluated according to progression-free survival. We utilized ordered multiple classification logistic regression to determine the dominant factors leading to CBZ resistance. We analyzed the correlation between hemoglobin A1c (HbA1c) and progression-free survival using the Pearson correlation analysis.

Results: The regression analysis showed that DM was the only factor affecting CBZ resistance (p = 0.035; OR = 0.327; 95% CI, 0.115-0.926). Progression-free survival was 28.5 ± 21.2 months in the DM group and 66.0 ± 33.2 months in the non-DM group. The concentration of HbA1c in the blood was negatively correlated with progression-free survival (r = - 0.197; p = 0.014).

Conclusions: This study shows that blood glucose status is a significant factor contributing to the CBZ resistance in the treatment of TN. The progression-free survival of patients is affected by the status of DM and blood HbAlc levels.
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http://dx.doi.org/10.1007/s10143-020-01304-4DOI Listing
April 2021

Treatment of Pituitary and Other Tumours with Cabergoline: New Mechanisms and Potential Broader Applications.

Neuroendocrinology 2020 10;110(6):477-488. Epub 2019 Oct 10.

Center of Pituitary Tumour, Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,

Cabergoline is a dopamine agonist that has been used as the first-line treatment option for prolactin-secreting pituitary adenomas for several decades. It not only suppresses hormone production from these prolactinomas, but also causes tumour shrinkage. Recent studies revealed some novel mechanisms by which cabergoline suppresses tumour cell proliferation and induces cell death. In this article, we review the most recent findings in cabergoline studies, focusing on its anti-tumour function. These studies suggest the potential broader clinical use of cabergoline in the treatment of other tumours such as breast cancer, pancreatic neuroendocrine tumours, and lung cancer.
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http://dx.doi.org/10.1159/000504000DOI Listing
May 2021

Multimodality Imaging for Navigation in Endoscopic Transsphenoidal Surgeries.

J Neurol Surg A Cent Eur Neurosurg 2018 Nov 14;79(6):486-495. Epub 2018 Sep 14.

Department of Neurosurgery, Shanghai Jiao Tong University School of Medicine, Shanghai, Republic of China.

Background And Study Aims:  Computed tomography (CT) and magnetic resonance image (MRI) data have been widely used to for navigation in various neurosurgical operations. However, delicate intracranial structures cannot be displayed using only one imaging method. Navigation with multimodality imaging was developed to better visualize these structures in glioma removal, but whether it is useful in endoscopic transsphenoidal surgery is unknown. We describe our clinical experience using multimodality imaging for navigation in endoscopic transsphenoidal surgeries.

Material And Methods:  A total of 134 patients underwent endoscopic transsphenoidal surgery with navigation using multimodality imaging. CT and MR images were fused and processed to optimally visualize anatomical structures of the sphenoidal sinus and tumor.

Results:  Navigation with multimodality imaging offers a precise display of anatomical structures in the sphenoid sinus as compared with navigation based on either CT or MRI.

Conclusion:  Navigation with multimodality imaging is capable of providing optimized guidance during endoscopic transsphenoidal surgeries. The fused images allow precise visualization of sphenoidal sinus structures, lesions and tumors. This is valuable for increasing safety in cases of anatomical variations and potentially decreasing the rate of tumor recurrence.
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http://dx.doi.org/10.1055/s-0038-1666789DOI Listing
November 2018
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