Publications by authors named "Haihui Jiang"

39 Publications

Aqueous choline amino acid deep eutectic solvents.

J Chem Phys 2021 Jun;154(21):214504

School of Chemistry and Sydney Nano Institute, The University of Sydney, NSW 2006, Australia.

We have investigated the structure and phase behavior of biocompatible, aqueous deep eutectic solvents by combining choline acetate, hydrogen aspartate, and aspartate amino acid salts with water as the sole molecular hydrogen bond donor. Using contrast-variation neutron diffraction, interpreted via computational modeling, we show how the interplay between anion structure and water content affects the hydrogen bond network structure in the liquid, which, in turn, influences the eutectic composition and temperature. These mixtures expand the current range choline amino acid ionic liquids under investigation for biomass processing applications to include higher melting point salts and also explain how the ionic liquids retain their desirable properties in aqueous solution.
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http://dx.doi.org/10.1063/5.0052479DOI Listing
June 2021

Combining MGMT promoter pyrosequencing and protein expression to optimize prognosis stratification in glioblastoma.

Cancer Sci 2021 Jun 11. Epub 2021 Jun 11.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Pyrosequencing (PSQ) represents the golden standard for MGMT promoter status determination. Binary interpretation of results based on the threshold from the average of several CpGs tested would neglect the existence of the "gray zone". How to define the gray zone and reclassify patients in this subgroup remains to be elucidated. A consecutive cohort of 312 primary glioblastoma patients were enrolled. CpGs 74-81 in the promoter region of MGMT were tested by PSQ and the protein expression was assessed by immunohistochemistry (IHC). Receiver operating characteristic curves were constructed to calculate the area under the curves (AUC). Kaplan-Meier plots were used to estimate the survival rate of patients compared by the log-rank test. The optimal threshold of each individual CpG differed from 5% to 11%. Patients could be separated into the hypomethylated subgroup (all CpGs tested below the corresponding optimal thresholds, n = 126, 40.4%), hypermethylated subgroup (all CpGs tested above the corresponding optimal thresholds, n = 108, 34.6%), and the gray zone subgroup (remaining patients, n = 78, 25.0%). Patients in the gray zone harbored an intermediate prognosis. The IHC score instead of the average methylation levels could successfully predict the prognosis for the gray zone (AUC for overall survival, 0.653 and 0.519, respectively). Combining PSQ and IHC significantly improved the efficiency of survival prediction (AUC: 0.662, 0.648, and 0.720 for PSQ, IHC, and combined, respectively). Immunohistochemistry is a robust method to predict prognosis for patients in the gray zone defined by PSQ. Combining PSQ and IHC could significantly improve the predictive ability for clinical outcomes.
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http://dx.doi.org/10.1111/cas.15024DOI Listing
June 2021

Corrigendum: Distinguishing Pseudoprogression From True Early Progression in Isocitrate Dehydrogenase Wild-Type Glioblastoma by Interrogating Clinical, Radiological and Molecular Features.

Front Oncol 2021 19;11:700599. Epub 2021 May 19.

Department of Neurosurgery, National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

[This corrects the article DOI: 10.3389/fonc.2021.627325.].
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http://dx.doi.org/10.3389/fonc.2021.700599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171117PMC
May 2021

Differential Predictors and Clinical Implications Associated With Long-Term Survivors in IDH Wildtype and Mutant Glioblastoma.

Front Oncol 2021 13;11:632663. Epub 2021 May 13.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: Glioblastoma (GBM) is the most aggressive intracranial tumor which can be divided into two subtypes based on status of isocitrate dehydrogenase (IDH). A small fraction of patients after receiving standard treatment can be long-term survivors (LTS). This study was designed to disclose the predictors and clinical implications associated with LTS in IDH wildtype and mutant GBM.

Methods: Patients who survived beyond five years after diagnosis of GBM were defined as LTS, while those with a survival less than one year were defined as short-term survivors (STS). A total of 211 patients with diagnosis of GBM in Beijing Tiantan Hospital from January 2007 to January 2015 were enrolled, including 44 (20.9%) LTS and 167 (79.1%) STS. The clinical, radiological and molecular features between groups were systematically compared.

Results: Compared with STS, LTS were a subgroup of patients with a younger age at diagnosis (=0.006), a higher KPS score (=0.011), higher rates of cystic change (=0.037), O-methylguanine-DNA methyltransferase (MGMT) promoter methylation (=0.007), and IDH mutation (=0.049), and more likely to have undergone gross total resection (<0.001). Survival analysis demonstrated that LTS with wildtype IDH conferred a longer progression-free survival (66.0 27.0 months, =0.04), but a shorter post-progression survival (46.5 months not reached, =0.0001) than those of LTS with mutant IDH. LTS with mutant IDH showed a trend towards increased survival after receiving re-operation (=0.155) and reirradiation (=0.127), while this clinical benefit disappeared in the subset of LTS with wildtype IDH (>0.05).

Conclusion: The prognostic value and therapeutic implications associated with LTS in GBM population significantly differed on the basis of IDH status. Our findings provide a new approach for physicians to better understand the two subtypes of GBM, which may assist in making more tailored treatment decisions for patients.
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http://dx.doi.org/10.3389/fonc.2021.632663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155513PMC
May 2021

Combination of Immunotherapy and Radiotherapy for Recurrent Malignant Gliomas: Results From a Prospective Study.

Front Immunol 2021 7;12:632547. Epub 2021 May 7.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: World Health Organization (WHO) grade IV glioma remains one of the most lethal tumors with a dismal prognosis and inevitable recurrence. We evaluated the safety and efficacy of immunotherapy with radiotherapy in this population of patients.

Methods: This study was a single-arm, open-label, phase I trial based on patients with recurrent WHO grade IV glioma. Patients were treated with intracranial and systemic immunoadjuvants in combination with low-dose reirradiation. The primary endpoint of the present trial was safety. Secondary endpoints were overall survival (OS) and progression-free survival (PFS). This trial is registered at ClinicalTrials.gov, NCT03392545.

Results: Thirty patients were enrolled. The most common adverse events (AEs) were fever (66.7%), vomiting (33.3%), headache (30.0%), and fatigue (23.3%). Only a single patient experienced grade 3 fever, and no grade 4 AEs or deaths related to treatment were observed. Of the 30 patients, 1 (3.3%) had a complete response, 5 (16.7%) had a partial response, 9 (30.0%) had stable disease, and 15 (50.0%) had progressive disease, resulting in an objective response rate of 20.0%. The median PFS of the entire cohort was 88.0 (61.0-254.0) days, and the median OS was 362.0 (197.0-601.0) days. Patients could be divided into responders and non-responders, and these groups exhibited a significant difference in terms of survival time, T lymphocyte subsets, frequency of cell division cycle 27 (CDC27) mutation status, and CD15 and CD68 expression (<0.05).

Conclusion: The combination of immunotherapy and radiotherapy is well tolerated and may provide clinical benefit for patients with recurrent WHO grade IV glioma. A prospective phase II study is needed to further validate the efficacy of our therapeutic regimen.
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http://dx.doi.org/10.3389/fimmu.2021.632547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138184PMC
May 2021

The combination of sesamol and clofibric acid moieties leads to a novel potent hypolipidemic agent with antioxidant, anti-inflammatory and hepatoprotective activity.

Bioorg Med Chem Lett 2021 Jul 17;44:128121. Epub 2021 May 17.

Shaanxi Traffic Hospital, 276 Daxue South Road, Beilin District, Xi'an, Shannxi Province 710068, People's Republic of China. Electronic address:

Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P < 0.01) and TC by 35.1% (P < 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway.
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http://dx.doi.org/10.1016/j.bmcl.2021.128121DOI Listing
July 2021

Distinguishing Pseudoprogression From True Early Progression in Isocitrate Dehydrogenase Wild-Type Glioblastoma by Interrogating Clinical, Radiological, and Molecular Features.

Front Oncol 2021 20;11:627325. Epub 2021 Apr 20.

Department of Neurosurgery, National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Pseudoprogression (PsP) mimics true early progression (TeP) in conventional imaging, which poses a diagnostic challenge in glioblastoma (GBM) patients who undergo standard concurrent chemoradiation (CCRT). This study aimed to investigate whether perioperative markers could distinguish and predict PsP from TeP in isocitrate dehydrogenase (IDH) wild-type GBM patients. New or progressive gadolinium-enhancing lesions that emerged within 12 weeks after CCRT were defined as early progression. Lesions that remained stable or spontaneously regressed were classified as PsP, otherwise persistently enlarged as TeP. Clinical, radiological, and molecular information were collected for further analysis. Patients in the early progression subgroup were divided into derivation and validation sets (7:3, according to operation date). Among 234 consecutive cases enrolled in this retrospective study, the incidences of PsP, TeP, and neither patterns of progression (nP) were 26.1% (61/234), 37.6% (88/234), and 36.3% (85/234), respectively. In the early progression subgroup, univariate analysis demonstrated female (: 2.161, = 0.026), gross total removal (GTR) of the tumor (: 6.571, < 001), located in the frontal lobe (: 2.561, = 0.008), non-subventricular zone (SVZ) infringement (: 10.937, < 0.001), and methylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter (mMGMTp) (: 9.737, < 0.001) were correlated with PsP, while GTR, non-SVZ infringement, and mMGMTp were further validated in multivariate analysis. Integrating quantitative MGMTp methylation levels from pyrosequencing, GTR, and non-SVZ infringement showed the best discriminative ability in the random forest model for derivation and validation set (AUC: 0.937, 0.911, respectively). Furthermore, a nomogram could effectively evaluate the importance of those markers in developing PsP (C-index: 0.916) and had a well-fitted calibration curve. Integrating those clinical, radiological, and molecular features provided a novel and robust method to distinguish PsP from TeP, which was crucial for subsequent clinical decision making, clinical trial enrollment, and prognostic assessment. By in-depth interrogation of perioperative markers, clinicians could distinguish PsP from TeP independent from advanced imaging.
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http://dx.doi.org/10.3389/fonc.2021.627325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093388PMC
April 2021

Role of circulating tumor cell detection in differentiating tumor recurrence from treatment necrosis of brain gliomas.

Biosci Trends 2021 May 29;15(2):107-117. Epub 2021 Apr 29.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Differentiating treatment necrosis from tumor recurrence poses a diagnostic conundrum for many clinicians in neuro-oncology. To investigate the potential role of circulating tumor cells (CTCs) detection in differentiating tumor recurrence and treatment necrosis in brain gliomas, we retrospectively analyzed the data of 22 consecutive patients with tumor totally removed and new enhancing mass lesion(s) showed on MRI after initial radiotherapy. The 22 patients were finally classified into tumor recurrence group (n = 10) and treatment necrosis group (n = 12), according to evidence from the clinical course (n = 11) and histological confirmation (n = 11). All 22 patients received CTCs detection, and DSC-MRP and 11C-MET-PET were performed on 20 patients (90.9%) and 17patients (77.3%) respectively. The data of the diagnosis efficacy to differentiate the two lesions by CTC detection, MPR and PET were analyzed by ROC analysis. The mean CTCs counts were significantly higher in the tumor recurrence group (6.10 ± 3.28) compared to the treatment necrosis group (1.08 ± 2.54, p < 0.001). The ROC curve showed that an optimized cell count threshold of 2 had 100% sensitivity and 91.2% specificity with AUC = 0.933 to declare tumor recurrence. The diagnostic efficacy of CTC detection was superior to rCBV of DSC-MRP and rSUV in MET-PET. Furthermore, we observed that CTCs detection could have a potential role in predicting tumor recurrence in one patient. Our research results preliminarily showed the potential value of CTC detection in differentiating treatment necrosis from tumor recurrence in brain gliomas, and is worthy of further confirmation with large samples involved.
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http://dx.doi.org/10.5582/bst.2021.01017DOI Listing
May 2021

Higher Cho/NAA Ratio in Postoperative Peritumoral Edema Zone Is Associated With Earlier Recurrence of Glioblastoma.

Front Neurol 2020 4;11:592155. Epub 2020 Dec 4.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

To explore the prognostic significance of metabolic parameters in postoperative peritumoral edema zone (PEZ) of patients with glioblastoma (GBM) based on proton magnetic resonance spectroscopy (MRS). The postoperative MRS data of 67 patients with GBM from Beijing Tiantan Hospital were retrospectively reviewed. Metabolite ratios including Cho/NAA, Cho/Cr, and NAA/Cr in both postoperative PEZ and contralateral normal brain region were recorded. Log-rank analysis and Cox regression model were used to identify parameters correlated with progression-free survival (PFS) and overall survival (OS). Compared with the contralateral normal brain region, postoperative PEZ showed a lower ratio of NAA/Cr (1.20 ± 0.42 vs. 1.81 ± 0.48, < 0.001), and higher ratios of Cho/Cr and Cho/NAA (1.36 ± 0.44 vs. 1.02 ± 0.27, < 0.001 and 1.32 ± 0.59 vs. 0.57 ± 0.14, < 0.001). Both the ratios of Cho/NAA and NAA/Cr were identified as prognostic factors in univariate analysis ( < 0.05), while only Cho/NAA ≥ 1.31 was further confirmed as an independent risk factor for early recurrence in the Cox regression model ( < 0.01). According to the factors of MGMT promoter unmethylation, without radiotherapy and Cho/NAA ≥ 1.31, a prognostic scoring scale for GBM was established, which could divide patients into low-risk, moderate-risk, and high-risk groups. There was a significant difference of survival rate between the three groups ( < 0.001). Higher Cho/NAA ratio in the postoperative PEZ of GBM predicts earlier recurrence and is associated with poor prognosis. The prognostic scoring scale based on clinical, molecular and metabolic parameters of patients with GBM can help doctors to make more precise prediction of survival time and to adjust therapeutic regimens.
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http://dx.doi.org/10.3389/fneur.2020.592155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747764PMC
December 2020

Classification of Progression Patterns in Glioblastoma: Analysis of Predictive Factors and Clinical Implications.

Front Oncol 2020 3;10:590648. Epub 2020 Nov 3.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: This study was designed to explore the progression patterns of IDH-wildtype glioblastoma (GBM) at first recurrence after chemoradiotherapy.

Methods: Records from 247 patients who underwent progression after diagnosis of IDH-wildtype GBM was retrospectively reviewed. Progression patterns were classified as either local, distant, subependymal or leptomeningeal dissemination based on the preoperative and serial postoperative radiographic images. The clinical and molecular characteristics of different progression patterns were analyzed.

Results: A total of 186 (75.3%) patients had local progression, 15 (6.1%) patients had distant progression, 33 (13.3%) patients had subependymal dissemination, and 13 (5.3%) patients had leptomeningeal dissemination. The most favorable survival occurred in patients with local progression, while no significant difference of survival was found among patients with distant progression, subependymal or leptomeningeal dissemination who were thereby reclassified into non-local group. Multivariable analysis showed that chemotherapy was a protective factor for non-local progression, while gender of male, subventricular zone (SVZ) involvement and O-methylguanine-DNA-methyltransferase (MGMT) promoter methylation were confirmed as risk factors for non-local progression ( < 0.05). Based on the factors screened by multivariable analysis, a nomogram was constructed which conferred high accuracy in predicting non-local progression. Patients in non-local group could be divided into long- and short-term survivors who differed in the rates of SVZ involvement, MGMT promoter methylation and reirradiation ( < 0.05), and a nomogram integrating these factors showed high accuracy in predicting long-term survivors.

Conclusion: Patients harboring different progression patterns conferred distinct clinical and molecular characteristics. Our nomograms could provide theoretical references for physicians to make more personalized and precise treatment decisions.
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http://dx.doi.org/10.3389/fonc.2020.590648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673412PMC
November 2020

Fatigue-Resistant, Notch-Insensitive Zwitterionic Polymer Hydrogels with High Self-Healing Ability.

Chempluschem 2020 09;85(9):2158-2165

School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, P. R. China.

Introducing self-healing properties into hydrogels can prolong their application lifetime. However, achieving mechanical strength without sacrificing self-healing properties is still a major challenge. We prepared a series of zwitterionic polymer hydrogels by random copolymerization of zwitterionic ionic monomer (SBMA), cationic monomer (DAC) and hydrophilic monomer (HEMA). The ionic bonds and hydrogen bonds formed in the hydrogels can efficiently dissipate energy and rebuild the network. The resulting hydrogels show high mechanical strength (289-396 KPa of fracture stress, 433-864 % of fracture stress) and have great fatigue resistance. The hydrogel with a 1 : 1 molar ratio of SBMA:DAC possesses the best self-healing properties (self-healing efficiency up to 96.5 % at room temperature for 10 h). The self-healing process is completely spontaneous and does not require external factors to assist. In addition, the hydrogel also possesses notch insensitivity with a fracture energy of 12000 J m . After combining the conductivity of RGO aerogel, the hydrogel/RGO composites show good strain sensitivity with high reliability and self-healing ability, which has certain significance in broadening the application of these zwitterionic hydrogels.
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http://dx.doi.org/10.1002/cplu.202000520DOI Listing
September 2020

The correlation of fractional anisotropy parameters with Ki-67 index, and the clinical implication in grading of non-enhancing gliomas and neuronal-glial tumors.

Magn Reson Imaging 2020 01 20;65:129-135. Epub 2019 Oct 20.

Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY, USA.

Purpose: To investigate the correlation between the FA parameters and Ki-67 labeling index, and their diagnostic performance in grading supratentorial non-enhancing gliomas and neuronal-glial tumors (GNGT).

Methods: This institutional review board-approved, Health Insurance Portability and Accountability (HIPAA) compliant retrospective study enrolled 35 patients, including 19 with low grade GNGT and 16 with high grade GNGT. The mean FA, maximal FA and mean maximal FA values derived from diffusion tensor imaging were measured. The correlation between the FA parameters and the Ki-67 labeling index was assessed by Spearman rank test. The receiver operating characteristic curve analysis and multivariate logistic regression analysis were performed to detect the optimal imaging parameters in grading GNGT.

Results: The three FA parameters of low grade GNGT were significantly lower than the high grade GNGT (p < 0.001). The mean FA, maximal FA and mean maximal FA had significant positive correlation with Ki-67 labeling index (p = 0.001, p < 0.001, p < 0.001 respectively). The maximal FA showed a higher sensitivity and specificity in grading of non-enhancing GNGT with specificity of 78.9%, sensitivity of 100.0%, respectively.

Conclusions: The FA parameters correlated with Ki-67 labeling index, and were useful surrogates in preoperative grading supratentorial non-enhancing GNGT.
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http://dx.doi.org/10.1016/j.mri.2019.10.009DOI Listing
January 2020

Diffuse midline glioma with H3 K27M mutation: a comparison integrating the clinical, radiological, and molecular features between adult and pediatric patients.

Neuro Oncol 2020 05;22(5):e1-e9

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: Diffuse midline glioma (DMG), H3 K27M mutant, occurs in both adult and pediatric populations. The characteristics of the 2 DMG groups were systematically explored in this study.

Methods: H3 K27M-mutant DMG was diagnosed in 116 patients at Beijing Tiantan Hospital from May 2016 to December 2018 who were included in our study. Patients were classified into an adult group (n = 57; 49.1%) and a pediatric group (n = 59; 50.9%). Clinical, radiological, and molecular features were compared between the groups. Univariate and multivariate analyses were performed to identify prognostic factors.

Results: Compared with the adult group, pediatric patients had a younger age (8.9 ± 4.1 y vs 35.1 ± 11.8 y, P < 0.001), a lower preoperative Karnofsky performance scale score (62.9 ± 15.5 vs 72.1 ± 16.5, P = 0.004), a lower rate of total resection (5.7% vs 26.8%, P = 0.009), a larger tumor size (4.4 ± 0.9 vs 3.9 ± 1.5 cm, P = 0.045), a higher Ki-67 index (63.0% vs 37.8%, P = 0.047), and higher rates of postoperative cranial nerve palsy (61.0% vs 36.8%, P = 0.009) and ataxia (45.8% vs 26.3%, P = 0.029). Adult DMG was located predominantly in the thalamus, while the predilection site for pediatric DMG was brainstem (P < 0.001). Kaplan-Meier plot showed that the median survival of adult and pediatric DMG was 16.0 (9.7-22.3) months and 10.0 (8.3-11.7) months, respectively, which imparted a significant difference (P = 0.008). Age at diagnosis, radiotherapy, and motor deficit were confirmed as independent prognostic factors according to the multivariate analysis (P < 0.05).

Conclusion: Compared with adult patients, children with H3 K27M-mutant DMG confer distinct clinical, radiological, and molecular characteristics and have a dismal prognosis. Radiotherapy is an independent factor associated with prolonged survival.
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http://dx.doi.org/10.1093/neuonc/noz152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962140PMC
May 2020

A soft ring oscillator.

Sci Robot 2019 Jun;4(31)

Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford St., Cambridge, MA 02138, USA.

Periodic actuation of multiple soft, pneumatic actuators requires coordinated function of multiple, separate components. This work demonstrates a soft, pneumatic ring oscillator that induces temporally coordinated periodic motion in soft actuators using a single, constant-pressure source, without hard valves or electronic controls. The fundamental unit of this ring oscillator is a soft, pneumatic inverter (an inverting Schmitt trigger) that switches between its two states ("on" and "off") using two instabilities in elastomeric structures: buckling of internal tubing and snap-through of a hemispherical membrane. An odd number of these inverters connected in a loop produces the same number of periodically oscillating outputs, resulting from a third, system-level instability; the frequency of oscillation depends on three system parameters that can be adjusted. These oscillatory output pressures enable several applications, including undulating and rolling motions in soft robots, size-based particle separation, pneumatic mechanotherapy, and metering of fluids. The soft ring oscillator eliminates the need for hard valves and electronic controls in these applications.
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http://dx.doi.org/10.1126/scirobotics.aaw5496DOI Listing
June 2019

Super-early initiation of temozolomide prolongs the survival of glioblastoma patients without gross-total resection: a retrospective cohort study.

J Neurooncol 2019 Aug 7;144(1):127-135. Epub 2019 Jun 7.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing Key Laboratory of Brain Tumor, #119 Fanyang Road, Fengtai District, Beijing, 100070, China.

Objective: The optimal timing of chemoradiotherapy in patients with newly diagnosed glioblastoma (GBM) remains unclear. In this study, we explored the clinical efficacy of super-early initiation of temozolomide (TMZ) in the treatment interval from surgery to radiotherapy.

Methods: We retrospectively reviewed the clinical data of 375 patients with GBM in our institution from 2012 to 2018. One hundred and sixty-three patients received super-early TMZ within 7 days after craniotomy based on standard Stupp protocol (super-early group, SEG), while two hundred and twelve patients underwent standard Stupp protocol alone (control group, CG). We performed propensity score matching (PSM) to reduce patient selection bias between the two groups.

Results: Before PSM, both median progression-free survival (PFS) and overall survival (OS) of patients in SEG were longer than those in CG (PFS 11.5 vs. 9.0 months, P = 0.0384 and OS 23.0 vs. 17.0 months, P = 0.0014). After PSM, the clinical efficacy of super-early initiation of TMZ only remained significant in term of OS, which was further validated in Cox hazard proportional model (HR = 0.583, 95% CI 0.384-0.884, P = 0.011). In the subgroup analysis, patients without gross total resection (GTR) or with O-methylguanine DNA methyltransferase promoter methylation could benefit from super-early initiation of TMZ in both PFS and OS (P < 0.05). No significant difference of treatment emerging adverse events was observed between the two groups (P > 0.05).

Conclusions: This retrospective study highlights that super-early initiation of TMZ in newly diagnosed GBM may confer to survival benefit, especially for those without GTR.
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http://dx.doi.org/10.1007/s11060-019-03211-1DOI Listing
August 2019

Prognostic implications of epidermal growth factor receptor variant III expression and nuclear translocation in Chinese human gliomas.

Chin J Cancer Res 2019 Feb;31(1):188-202

Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

Objective: To determine the prognostic implications and clinical significance of epidermal growth factor receptor variant III (EGFRvIII) expression and EGFRvIII nuclear translocation in Chinese human gliomas.

Methods: We retrospectively examined EGFRvIII expression and EGFRvIII nuclear translocation using immunohistochemistry in specimens of 240 Chinese patients with glioma, including 84 World Health Organization (WHO) II gliomas, 84 WHO III gliomas and 72 glioblastomas (WHO IV). Factors that correlated with EGFRvIII and EGFRvIII nuclear translocation expression were analyzed by the Chi-square test. Kaplan-Meier methodology and Cox regression were used for the survival analysis.

Results: Log-rank tests showed that patient age, Karnofsky performance scale (KPS) score, tumor grade, EGFRvIII expression, EGFRvIII nuclear translocation, 1p/19q codeletion, isocitrate dehydrogenase (IDH) mutation, Ki-67 labeling index and O6-methylguanine-DNA methyltransferase (MGMT) status (P<0.05) were significantly correlated with overall survival (OS) time. Multivariate Cox regression analysis revealed that patient age, tumor grade, EGFRvIII nuclear translocation, 1p/19q codeletion, and IDH mutation (P<0.05) were significantly correlated with OS. Patients with a high level of EGFRvIII nuclear translocation (≥7%) had both significantly shorter OS [hazard ratio (HR): 1.920, 95% confidence interval (95% CI): 1.228-3.003, P=0.004] and progression-free survival (PFS) times (HR: 1.661, 95% CI: 1.116-2.471, P=0.012) than those with a low level of EGFRvIII nuclear translocation (<7%).

Conclusions: A high level of EGFRvIII nuclear translocation in glioma is an independent factor indicating a poor prognosis, but EGFRvIII expression is not an independent clinical prognostic factor. The level of EGFRvIII nuclear translocation maybe a novel and crucial prognostic biomarker in glioma.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2019.01.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433583PMC
February 2019

Digital logic for soft devices.

Proc Natl Acad Sci U S A 2019 04 28;116(16):7750-7759. Epub 2019 Mar 28.

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138;

Although soft devices (grippers, actuators, and elementary robots) are rapidly becoming an integral part of the broad field of robotics, autonomy for completely soft devices has only begun to be developed. Adaptation of conventional systems of control to soft devices requires hard valves and electronic controls. This paper describes completely soft pneumatic digital logic gates having a physical scale appropriate for use with current (macroscopic) soft actuators. Each digital logic gate utilizes a single bistable valve-the pneumatic equivalent of a Schmitt trigger-which relies on the snap-through instability of a hemispherical membrane to kink internal tubes and operates with binary high/low input and output pressures. Soft, pneumatic NOT, AND, and OR digital logic gates-which generate known pneumatic outputs as a function of one, or multiple, pneumatic inputs-allow fabrication of digital logic circuits for a set-reset latch, two-bit shift register, leading-edge detector, digital-to-analog converter (DAC), and toggle switch. The DAC and toggle switch, in turn, can control and power a soft actuator (demonstrated using a pneu-net gripper). These macroscale soft digital logic gates are scalable to high volumes of airflow, do not consume power at steady state, and can be reconfigured to achieve multiple functionalities from a single design (including configurations that receive inputs from the environment and from human users). This work represents a step toward a strategy to develop autonomous control-one not involving an electronic interface or hard components-for soft devices.
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http://dx.doi.org/10.1073/pnas.1820672116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475414PMC
April 2019

Proliferation-dominant high-grade astrocytoma: survival benefit associated with extensive resection of FLAIR abnormality region.

J Neurosurg 2019 Mar 22;132(4):998-1005. Epub 2019 Mar 22.

1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, and China National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, China; and.

Objective: The aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).

Methods: Clinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.

Results: Both the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WI with a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078-1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p = 0.86).

Conclusions: VFLAIR/VCE-T1WI is an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.
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http://dx.doi.org/10.3171/2018.12.JNS182775DOI Listing
March 2019

Supratentorial high-grade astrocytoma with leptomeningeal spread to the fourth ventricle: a lethal dissemination with dismal prognosis.

J Neurooncol 2019 Apr 2;142(2):253-261. Epub 2019 Jan 2.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Purpose: Leptomeningeal spread to the fourth ventricle (LSFV) from supratentorial high-grade astrocytoma (HGA) is rarely investigated. The incidence and prognostic merit of LSFV were analyzed in this study.

Methods: A consecutive cohort of 175 patients with pathologically diagnosed HGA according to the 2016 WHO classification of brain tumors was enrolled. LSFV was defined as radiological occupation in the fourth ventricle at the moment of initial progression. Clinical, radiological, and pathological data were analyzed to explore the difference between HGA patients with and without LSFV.

Results: There were 18 of 175 (10.3%) HGAs confirmed with LSFV. The difference of survival rate between patients with LSFV or not was significant in both overall survival (OS) (14.5 vs. 24 months, P =  0.0007) and post progression survival (PPS) (6.0 vs. 11.5 months, P = 0.0004), while no significant difference was observed in time to progression (TTP) (8.5 months vs. 9.5 months P = 0.6795). In the Cox multivariate analysis, LSFV was confirmed as an independent prognostic risk factor for OS (HR 2.06, P = 0.010). LSFV was correlated with younger age (P = 0.044), ventricle infringement of primary tumor (P < 0.001) and higher Ki-67 index (P = 0.013) in further analysis, and the latter two have been validated in the Logistic regression analysis (OR 18.16, P = 0.006; OR 4.04, P = 0.012, respectively).

Conclusion: LSFV was indicative of end-stage for supratentorial HGA patients, which shortened patients' PPS and OS instead of TTP. It's never too cautious to alert this lethal event when tumor harbored ventricle infringement and higher Ki-67 index in routine clinical course.
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http://dx.doi.org/10.1007/s11060-018-03086-8DOI Listing
April 2019

Structural Design of Ionic Liquids for Optimizing Aromatic Dissolution.

ChemSusChem 2019 Jan 9;12(1):270-274. Epub 2018 Nov 9.

School of Chemistry and Sydney Nano Institute, The University of Sydney, NSW, 2006, Australia.

Certain protic ionic liquids (PILs) are potentially low-cost, high-efficiency solvents for the extraction and processing of aromatic compounds. To understand the key design features of PILs that determine solubility selectivity at the atomic level, neutron diffraction was used to compare the bulk structure of two PILs with and without an aromatic solute, guaiacol (2-methoxyphenol). Guaiacol is a common lignin residue in biomass processing, and a model compound for anisole- or phenol-based food additives and drug precursors. Although the presence of amphiphilic nanostructure is important to facilitate the dissolution of solute nonpolar moieties, the local geometry and competitive interactions between the polar groups of the cation, anion, and solute are found to also strongly influence solvation. Based on these factors, a framework is presented for the design of PIL structure to minimize competition and to enhance driving forces for the dissolution of small aromatic species.
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http://dx.doi.org/10.1002/cssc.201802016DOI Listing
January 2019

1q/19p co-polysomy predicts longer survival in patients with astrocytic gliomas.

Oncotarget 2017 Sep 16;8(40):67104-67116. Epub 2017 May 16.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Recently, we reported that 1q/19p co-polysomy predicted poor prognosis in oligodendroglial tumors. In this study, we aimed to retrospectively analyze the prognostic significance of 1q/19p polysomy in two large cohorts of astrocytic gliomas classified by the 2007 and 2016 WHO classification of tumors of the central nervous system. 1q/19p polysomy was detected using the FISH method, and factors that correlated with polysomy were analyzed by logistic regression. Survival analysis was used to identify independent prognostic factors correlated with survival. In the WHO astrocytic glioma cohort (N=421), co-polysomy was associated with a younger age, whereas single polysomy was associated with higher tumor grades and a higher Ki-67 index (<0.05). Co-polysomy predicted longer survival, and single polysomy predicted shorter survival (<0.05). In multivariate analysis, co-polysomy maintained an independent prognostic impact on survival (=0.001) after adjustment for age, KPS, grade, removal degree, tumor size, Ki-67 index, and IDH1/2. In the WHO cohort (N=572), we validated the prognostic merit of co-polysomy after adjusting for related factors. In conclusion, 1q/19p co-polysomy added prognostic information in cases of astrocytic glioma and could be used for molecular stratification of this disease.
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http://dx.doi.org/10.18632/oncotarget.17947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620159PMC
September 2017

Dichotomous Well-defined Nanostructure with Weakly Arranged Ion Packing Explains the Solvency of Pyrrolidinium Acetate.

J Phys Chem B 2017 07 28;121(27):6610-6617. Epub 2017 Jun 28.

School of Chemistry and Australian Institute for Nanoscale Science and Technology, The University of Sydney , Sydney, NSW 2006, Australia.

Pyrrolidinium ionic liquids, especially pyrrolidinium acetate (PyrrAc), have demonstrated outstanding capacity for extracting lignin from biomass, as electrolytes for fuel cells and lithium ion batteries and as solvents for acid-catalyzed reactions. In this work we show that the unusual liquid nanostructure of PyrrAc is the key to its versatility as a solvent compared to other ionic liquids. Neutron diffraction with multiple H/D isotopic substitutions reveals that the bulk nanostructure of PyrrAc is a bicontinuous network of interpenetrating polar and apolar domains. However, the arrangement of groups in both domains is strikingly different from that found in other ionic liquids. In the apolar regions, the pyrrolidinium rings are highly intercalated and disordered, with no preferred alignment between adjacent pyrrolidinium rings, which distinguishes it from both π-π stacking seen in imidazolium or pyridinium ionic liquids, and the tail-tail bilayer-like arrangements in linear alkylammonium ionic liquids. The H-bond network within the polar domain extends only to form finite clusters, with long bent H-bonds to accommodate electrostatics. Therefore, while PyrrAc unquestionably has well-defined amphiphilic nanostructure, the disordered arrangement of groups in the polar and apolar domains enables it to accommodate a wide variety of solutes. The combination of well-defined polar/apolar nanostructure, but disordered arrangements of groups within domains, is therefore the origin of PyrrAc's capacity for lignin extraction and as an electrolyte.
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http://dx.doi.org/10.1021/acs.jpcb.7b03045DOI Listing
July 2017

Patient-Specific Resection Strategy of Glioblastoma Multiforme: Choice Based on a Preoperative Scoring Scale.

Ann Surg Oncol 2017 Jul 20;24(7):2006-2014. Epub 2017 Mar 20.

Department of Neurosurgery, Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Capital Medical University, Beijing, China.

Background: The real association between extent of resection and outcome in patients with glioblastoma multiforme (GBM) remains unclear.

Objective: The goal of this study was to disclose the effect of gross total resection on survival and establish a scale used for surgical decision making.

Methods: A retrospective review was undertaken of 416 patients who received operation for GBM from 2008 to 2015 in Beijing Tiantan Hospital. To reduce bias in patient selection, propensity score analysis was conducted and 99 pairs of matched GBMs were generated. Survival between different groups was compared using the Kaplan-Meier method, and independent predictors of survival were identified using the Cox proportional hazards model.

Results: Overall, the survival of patients undergoing GTR was significantly longer than those not undergoing GTR (12.0 vs. 9.0 months [p < 0.001] for progression-free survival [PFS], and 20.5 versus 16.0 months [p < 0.001] for overall survival [OS]). In the propensity model, the survival benefit of GTR remained significant, which has been further validated in the multivariate analysis (hazard ratio [HR] 0.613, 95% confidence interval [CI] 0.454-0.827 [p = 0.001] for PFS, and HR 0.475, 95% CI 0.343-0.659 [p < 0.001] for OS). Using a scoring scale based on age, epilepsy, location, tumor size, and Karnofsky performance score, patients were stratified into low-, moderate-, and high-risk cohorts. The survival benefit of GTR could be observed in the low- and moderate-risk cohorts but not the high-risk cohort.

Conclusion: GTR was an independent predictor of increased survival for patients with GBM. The risk scoring scale quantified the clinical significance of operation and helped us to project more personalized surgical strategies for individual patients.
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http://dx.doi.org/10.1245/s10434-017-5843-1DOI Listing
July 2017

Impact of epidemiological characteristics of supratentorial gliomas in adults brought about by the 2016 world health organization classification of tumors of the central nervous system.

Oncotarget 2017 Mar;8(12):20354-20361

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

The latest World Health Organization (WHO) classification of tumors of the central nervous system (CNS) integrates both histological and molecular features in the definition of diagnostic entities. This new approach enrolls novel entities of gliomas. In this study, we aimed to reveal the epidemiological characteristics, including age at diagnosis, gender ratio, tumor distribution and survival, of these new entities. We retrospectively reclassified 1210 glioma samples according to the 2016 CNS WHO diagnostic criteria. In our cohort, glioblastoma multiforme (GBM) with wildtype isocitrate dehydrogenase (IDH) was the most common malignant tumor in the brain. Almost all gliomas were more prevalent in males, especially in the cluster of WHO grade III gliomas and IDH-wildtype GBM. Age at diagnosis was directly proportional to tumor grade. With respect to the distribution by histology, we found that gliomas concurrent with IDH-mutant and 1p/19q-codeleted or with single IDH-mutant were mainly distributed in frontal lobe, while those with IDH-wildtype were dominant in temporal lobe. Lesions located in insular lobe were more likely to be IDH-mutant astrocytoma. In summary, our results elucidated the epidemiological characteristics as well as the regional constituents of these new gliomas entities, which could bring insights into tumorigenesis and personalized treatment of Chinese glioma population.
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http://dx.doi.org/10.18632/oncotarget.13555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386767PMC
March 2017

Circulating tumor cell is a common property of brain glioma and promotes the monitoring system.

Oncotarget 2016 Nov;7(44):71330-71340

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Brain glioma is the most common primary intracranial tumor characterized by dismal prognosis and frequent recurrence, yet a real-time and reliable biological approach to monitor tumor response and progression is still lacking. Recently, few studies have reported that circulating tumor cells (CTCs) could be detected in glioblastoma multiform (GBM), providing the possibility of its application in brain glioma monitoring system. But its application limits still exist, because the detection rate of CTCs is still low and was exclusively limited to high- grade gliomas. Here, we adopted an advanced integrated cellular and molecular approach of SE-iFISH to detect CTCs in the peripheral blood (PB) of patients with 7 different subtypes of brain glioma, uncovering the direct evidences of glioma migration. We identified CTCs in the PB from 24 of 31 (77%) patients with glioma in all 7 subtypes. No statistical difference of CTC incidence and count was observed in different pathological subtypes or WHO grades of glioma. Clinical data revealed that CTCs, to some extent, was superior to MRI in monitoring the treatment response and differentiating radionecrosis from recurrence of glioma. Conclusively, CTCs is a common property of brain gliomas of various pathological subtypes, which has provided an ultimate paradox for the hypothesis "soil and seed". It can be used to monitor the microenvironment of gliomas dynamically, which will be a meaningful complement to radiographic imaging.
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http://dx.doi.org/10.18632/oncotarget.11114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342081PMC
November 2016

Tumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendroglioma.

J Neurosurg 2016 10 15;125(4):995-1001. Epub 2016 Jan 15.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brian Tumor; and.

OBJECTIVE 1p/19q co-deletion is a well-established tumor cell-specific chromosomal abnormality in oligodendroglial tumors. The endothelial cells (ECs) of oligodendroglial tumor vessels are considered to be normal cells that do not acquire mutations. METHODS A total of 30 samples from 16 male and 14 female patients (median age of 46.5 years) with a histological diagnosis of primary anaplastic oligodendroglioma (AO) were collected in the study. The immunofluorescence technique was used to identify vascular ECs, and the 1p/19q status was detected with fluorescence in situ hybridization. Kaplan-Meier plots were compared using the log-rank method. RESULTS The ECs in AO had a higher 1p36 (detected signal) deletion rate than 1q25 (reference signal) (p < 0.01) and a higher 19q13 (detected signal) deletion rate than 19p13 (reference signal) (p < 0.01). The survival analysis results showed that both the progression-free survival (PFS) and overall survival (OS) of the patients with 1p/19q-co-deleted ECs were significantly longer than those with 1p/19q-intact ECs (PFS, p < 0.001; OS, p < 0.001). This correlation was validated by an independent cohort. In addition, the Cox regression model revealed that 1p/19q co-deletion in ECs was an independent prognostic factor (HR 0.056 [95% CI 0.012-0.261], p < 0.001 for PFS; HR 0.061 [95% CI 0.013-0.280], p < 0.01 for OS). CONCLUSIONS 1p/19q co-deletion and polysomy can be also found in the ECs of AO, which suggests that the ECs are, in part, tumor related and reflect a novel aspect of tumor angiogenesis.
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http://dx.doi.org/10.3171/2015.8.JNS15879DOI Listing
October 2016

1p/19q-driven prognostic molecular classification for high-grade oligodendroglial tumors.

J Neurooncol 2014 Dec 24;120(3):607-14. Epub 2014 Aug 24.

Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brian Tumor, Beijing, 100050, People's Republic of China.

The subjectivity in pathological diagnosis of anaplastic oligoastrocytoma (AOA) and uncertainty in designation of glioblastoma with oligodendroglioma component (GBMO) were two major dilemmas which puzzled neuro-pathologists and neurosurgeons. The present study was designed to project a molecular classification scheme based on the status of chromosome 1p and 19q. Patients (n = 117) with histological diagnosis of primary high-grade oligodendroglial tumors (HGOs) enrolled in the study. Fluorescence in situ hybridization (FISH) for chromosomes 1p and 19q was performed. Univariate analysis showed that higher tumor grade, 1p/19q maintenance and 1q/19p co polysomy were confirmed as risk factors in HGOs (P < 0.01). Accordingly, patients with HGOs were divided into four subtypes which conferred remarkably distinct prognosis based on the number of risk factors (0 risk factor: HGOs-1, 1 risk factor: HGOs-2, 2 risk factors: HGOs-3, 3 risk factors: HGOs-4). Cox regression model revealed that the tumor grade was no longer independently associated with survival, while the molecular classification scheme showed a marked prognostic significance (HR = 0.359, 95 % CI 0.261-0.494, P < 0.001 for progression-free survival (PFS); HR = 0.393, 95 % CI 0.283-0.546, P < 0.001 for overall survival (OS)). The classification scheme incorporating traditional pathology with molecular information can be served as a supplement of the current WHO classification system and contribute to the personalized treatment decision-making.
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http://dx.doi.org/10.1007/s11060-014-1593-0DOI Listing
December 2014

Amphiphilic self-assembly of alkanols in protic ionic liquids.

J Phys Chem B 2014 Aug 7;118(33):9983-90. Epub 2014 Aug 7.

School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia.

Strong cohesive forces in protic ionic liquids (PILs) can induce a liquid nanostructure consisting of segregated polar and apolar domains. Small-angle X-ray scattering has shown that these forces can also induce medium chain length n-alkanols to self-assemble into micelle- and microemulsion-like structures in ethylammonium (EA(+)) and propylammonium (PA(+)) PILs, in contrast to their immiscibility with both water and ethanolammonium (EtA(+)) PILs. These binary mixtures are structured on two distinct length scales: one associated with the self-assembled n-alkanol aggregates and the other with the underlying liquid nanostructure. This suggests that EA(+) and PA(+) enable n-alkanol aggregation by acting as cosurfactants, which EtA(+) cannot do because its terminating hydroxyl renders the cation nonamphiphilic. The primary determining factor for miscibility and self-assembly is the ratio of alkyl chain lengths of the alkanol and PIL cation, modulated by the anion type. These results show how ILs can support the self-assembly of nontraditional amphiphiles and enable the creation of new forms of soft matter.
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http://dx.doi.org/10.1021/jp504998tDOI Listing
August 2014

Polysomy of chromosomes 1 and 19: an underestimated prognostic factor in oligodendroglial tumors.

J Neurooncol 2014 Oct 10;120(1):131-8. Epub 2014 Jul 10.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, 100050, People's Republic of China.

The clinical significance of chromosomes 1 and 19 deletion was well established in oligodendroglial tumors (ODGs). This study was designed to evaluate the prognostic implication of chromosomes 1 and 19 polysomy in gliomas. 584 patients with histological diagnosis of primary gliomas enrolled in the study. Chromosomes 1 and 19 status was detected with fluorescence in situ hybridization (FISH). Of the 584 cases, the frequency of 1q and 19p polysomy in mixed gliomas was significantly higher than ODGs or astrocytic tumors (1q P = 0.032 and P = 0.044; 19p P = 0.024 and P = 0.027); the frequency of 1q and 19p polysomy in low-grade gliomas (WHO II) was relatively lower compared with WHO III or WHO IV (1q P = 0.097 and P = 0.026; 19p P = 0.04 and P = 0.002). 1q, 19p and co-polysomy were confirmed as risk factors conveyed unfavorable outcomes, which has been further validated in both anaplastic oligodendroglial tumors (AOGs) (P = 0.07, P = 0.028 and P = 0.054 for PFS; P = 0.007, P = 0.001 and P = 0.002 for OS, respectively) and glioblastomas with oligodendroglioma component (GBMOs) (P = 0.005, P < 0.001 and P < 0.001 for PFS; P = 0.136, P = 0.006 and P = 0.051 for OS, respectively). Based on chromosomes 1/19 co-deletion and co-polysomy, AOGs and GBMOs could be divided into three subgroups which harbored distinct prognosis (AOGs P < 0.001 for PFS and P < 0.001 for OS; GBMOs P < 0.001 for PFS and P = 0.012 for OS). Chromosomes 1/19 polysomy are potential prognostic factors which confer unfavorable outcomes. The molecular prognostic grouping model based on chromosomes 1/19 co-polysomy and co-deletion better predicts prognosis and provides a more reliable information for treatment decision-making.
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http://dx.doi.org/10.1007/s11060-014-1526-yDOI Listing
October 2014
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