Publications by authors named "Xiaohui Ren"

102 Publications

Triggering Water and Methanol Activation for Solar-Driven H Production: Interplay of Dual Active Sites over Plasmonic ZnCu Alloy.

J Am Chem Soc 2021 Jul 29. Epub 2021 Jul 29.

Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo, Hokkaido 060-0814, Japan.

Methanol steam reforming (MSR) is a promising reaction that enables efficient production and safe transportation of hydrogen, but it requires a relatively high temperature to achieve high activity, leading to large energy consumption. Here, we report a plasmonic ZnCu alloy catalyst, consisting of plasmonic Cu nanoparticles with surface-deposited Zn atoms, for efficient solar-driven MSR without additional thermal energy input. Experimental results and theoretical calculations suggest that Zn atoms act not only as the catalytic sites for water reduction with lower activation energy but also as the charge transfer channel, pumping hot electrons into water molecules and subsequently resulting in the formation of electron-deficient Cu for methanol activation. These merits together with photothermal heating render the optimal ZnCu catalyst a high H production rate of 328 mmol g h with a solar energy conversion efficiency of 1.2% under 7.9 Suns irradiation, far exceeding the reported conventional photocatalytic and thermocatalytic MSR. This work provides a potential strategy for efficient solar-driven H production and various other energy-demanding industrial reactions through designing alloy catalysts.
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http://dx.doi.org/10.1021/jacs.1c04315DOI Listing
July 2021

KDM4 Orchestrates Epigenomic Remodeling of Senescent Cells and Potentiates the Senescence-Associated Secretory Phenotype.

Nat Aging 2021 May 13;1(5):454-472. Epub 2021 May 13.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Cellular senescence restrains the expansion of neoplastic cells through several layers of regulation. We report that the histone H3-specific demethylase KDM4 is expressed as human stromal cells undergo senescence. In clinical oncology, upregulated KDM4 and diminished H3K9/H3K36 methylation correlate with poorer survival of prostate cancer patients post-chemotherapy. Global chromatin accessibility mapping via ATAC-seq, and expression profiling through RNA-seq, reveal global changes of chromatin openness and spatiotemporal reprogramming of the transcriptomic landscape, which underlie the senescence-associated secretory phenotype (SASP). Selective targeting of KDM4 dampens the SASP of senescent stromal cells, promotes cancer cell apoptosis in the treatment-damaged tumor microenvironment (TME), and prolongs survival of experimental animals. Our study supports dynamic changes of H3K9/H3K36 methylation during senescence, identifies an unusually permissive chromatin state, and unmasks KDM4 as a key SASP modulator. KDM4 targeting presents a novel therapeutic avenue to manipulate cellular senescence and limit its contribution to age-related pathologies including cancer.
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http://dx.doi.org/10.1038/s43587-021-00063-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277122PMC
May 2021

Association between SNPs and hepatotoxicity in patients with primary central nervous system lymphoma on high-dose methotrexate therapy.

J Pharm Pharmacol 2021 Jul 13. Epub 2021 Jul 13.

Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R. China.

Objectives: This study aims to evaluate the association between polymorphisms of methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity in Chinese patients with primary central nervous system lymphoma.

Methods: Sixty-five patients in 411 treatment courses were enrolled and their toxicities were evaluated. The association between 30 candidate SNPs from 20 methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity was analysed by PLINK and logistic regression.

Key Findings: TYMS 6 bp DI + II (rs151264360; OR, 0.41; 95% CI, 0.25-0.66; P = 0.00029), MTHFD1 1958 GA + AA (rs2236225; OR, 0.55; 95% CI, 0.33-0.91; P = 0.020) and CCND1 870 GA + GG (rs9344; OR, 0.42; 95% CI, 0.24-0.73; P = 0.0024) had less risk of hepatotoxicity compared with their homozygotes (DD, GG and AA, respectively), while ABCC2 intron 29 GA + GG (rs3740065; OR, 3.14; 95% CI, 1.89-5.20; P = 0.00001) was more prevalent in patients with hepatotoxicity than TT.

Conclusions: TYMS 6 bp DI + II, MTHFD1 1958 GA + AA, CCND1 870 GA + GG genotypes were associated with a lower probability of hepatotoxicity in patients with primary central nervous system lymphoma on high-dose methotrexate therapy, and ABCC2 intron 29 GA + GG was correlated with increased risk of hepatotoxicity.
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http://dx.doi.org/10.1093/jpp/rgab099DOI Listing
July 2021

Plasmonic photothermal catalysis for solar-to-fuel conversion: current status and prospects.

Chem Sci 2021 Mar 12;12(16):5701-5719. Epub 2021 Mar 12.

International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS) 1-1 Namiki Tsukuba Ibaraki 305-0044 Japan

Solar-to-fuel conversion through photocatalytic processes is regarded as promising technology with the potential to reduce reliance on dwindling reserves of fossil fuels and to support the sustainable development of our society. However, conventional semiconductor-based photocatalytic systems suffer from unsatisfactory reaction efficiencies due to limited light harvesting abilities. Recent pioneering work from several groups, including ours, has demonstrated that visible and infrared light can be utilized by plasmonic catalysts not only to induce local heating but also to generate energetic hot carriers for initiating surface catalytic reactions and/or modulating the reaction pathways, resulting in synergistically promoted solar-to-fuel conversion efficiencies. In this perspective, we focus primarily on plasmon-mediated catalysis for thermodynamically uphill reactions converting CO and/or HO into value-added products. We first introduce two types of mechanism and their applications by which reactions on plasmonic nanostructures can be initiated: either by photo-induced hot carriers (plasmonic photocatalysis) or by light-excited phonons (photothermal catalysis). Then, we emphasize examples where the hot carriers and phonon modes act in concert to contribute to the reaction (plasmonic photothermal catalysis), with special attention given to the design concepts and reaction mechanisms of the catalysts. We discuss challenges and future opportunities relating to plasmonic photothermal processes, aiming to promote an understanding of underlying mechanisms and provide guidelines for the rational design and construction of plasmonic catalysts for highly efficient solar-to-fuel conversion.
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http://dx.doi.org/10.1039/d1sc00064kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179669PMC
March 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

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

Postoperative Long-Term Independence Among the Elderly With Meningiomas: Function Evolution, Determinant Identification, and Prediction Model Development.

Front Oncol 2021 5;11:639259. Epub 2021 Mar 5.

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

Background: Maintenance of postoperative long-term independence has value for older adults who undergo surgical procedures. However, independence has barely caught attention for the elderly with meningiomas. Preventing postoperative long-term independence decline in this population necessitates the identification of the factors related to this outcome and minimizing their implications. Therefore, we assessed the independence evolution and identified potential determinants and population.

Materials And Methods: From 2010 to 2016, elderly meningioma patients (≥65 years old) undergoing operation at Beijing Tiantan Hospital were included in our study. The primary outcome was 3-year (., long-term) postoperative independence measured by Karnofsky performance scale (KPS) score. We used univariate and multivariate analyses to determine the risk factors for postoperative long-term independence, and nomogram was established.

Results: A total of 470 patients were included eligibly. The distribution in each KPS was significantly different before and 3 years after resection ( < 0.001). Especially in patients with preoperative KPS 80 and 70, only 17.5 and 17.3% of the patients kept the same KPS after 3 years, and the remaining patients experienced significant polarization. The most common remaining symptom cluster correlated with postoperative long-term independence included fatigue (R = -0.795), memory impairment (R = -0.512), motor dysfunction (R = -0.636) and communication deficits (R = -0.501). Independent risk factors for postoperative long-term non-independence included: advanced age (70-74 65-69 OR: 2.631; 95% CI: 1.545-4.481 and ≥75 65-69 OR: 3.833; 95% CI: 1.667-8.812), recurrent meningioma (OR: 7.791; 95% CI: 3.202-18.954), location in the skull base (OR: 2.683; 95% CI: 1.383-5.205), tumor maximal diameter >6 cm (OR: 3.089; 95% CI: 1.471-6.488), nerves involved (OR: 3.144; 95% CI: 1.585-6.235), high risk of WHO grade and biological behavior (OR: 2.294; 95% CI: 1.193-4.408), recurrence during follow-up (OR: 10.296; 95% CI: 3.253-32.585), lower preoperative KPS (OR: 0.964; 95% CI: 0.938-0.991) and decreased KPS on discharge (OR: 0.967; 95% CI: 0.951-0.984) ( < 0.05). The discrimination and calibration of the nomogram revealed good predictive ability (C-index: 0.810).

Conclusion: Elderly meningioma patients might present significant polarization trend in maintaining long-term independence after surgery. Our findings will be helpful for guiding surgical management for the elderly with meningioma and provide proposals for early functional rehabilitation.
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http://dx.doi.org/10.3389/fonc.2021.639259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982808PMC
March 2021

Inhibition of Dot1L Alleviates Fulminant Hepatitis Through Myeloid-Derived Suppressor Cells.

Cell Mol Gastroenterol Hepatol 2021 23;12(1):81-98. Epub 2021 Jan 23.

Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Background & Aims: Fulminant hepatitis (FH) is a clinical syndrome characterized by sudden and severe liver dysfunction. Dot1L, a histone methyltransferase, is implicated in various physiologic and pathologic processes, including transcription regulation and leukemia. However, the role of Dot1L in regulating inflammatory responses during FH remains elusive.

Methods: Propionibacterium acnes (P. acnes)-primed, lipopolysaccharides (LPS)-induced FH was established in C57BL/6 mice and was treated with the Dot1L inhibitor EPZ-5676. Myeloid derived suppressor cells (MDSCs) were depleted by anti-Gr-1 antibody to evaluate their therapeutic roles in Dot1L treatment of FH. Moreover, peripheral blood of patients suffered with FH and healthy controls was collected to determine the expression profile of Dot1L-SOCS1-iNOS axis in their MDSCs.

Results: Here we identified that EPZ-5676, pharmacological inhibitor of Dot1L, attenuated the liver injury of mice subjected to FH. Dot1L inhibition led to decreased T helper 1 cell response and expansion of regulatory T cells (Tregs) during FH. Interestingly, Dot1L inhibition didn't directly target T cells, but dramatically enhanced the immunosuppressive function of MDSCs. Mechanistically, Dot1L inhibition epigenetically suppressed SOCS1 expression, thus inducing inducible nitric oxide synthase (iNOS) expression in a STAT1-dependent manner. Moreover, in human samples, the levels of Dot1L and SOCS1 expression were upregulated in MDSCs, accompanied by decreased expression of iNOS in patients with FH, compared with healthy controls.

Conclusions: Altogether, our findings established Dot1L as a critical regulator of MDSC immunosuppressive function for the first time, and highlighted the therapeutic potential of Dot1L inhibitor for FH treatment.
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http://dx.doi.org/10.1016/j.jcmgh.2021.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081916PMC
January 2021

Core-shell magnetic Ag-molecularly imprinted composite for surface enhanced Raman scattering detection of carbaryl.

J Environ Sci Health B 2021 8;56(3):222-234. Epub 2021 Jan 8.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, State Key Lab of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, China.

Surface-enhanced Raman scattering (SERS) is a promising technique for rapid detection of pesticide residues. However, conventional SERS substrates require extraction processes which are time consuming and they also lack selectivity, stability and reproducibility. Herein, we present a multifunctional stable zero-valent iron based core-shell substrate. It combines magnetic separation, selective adsorption by molecular imprinting technique and sensitive detection of carbaryl by SERS. The core-shell substrate was successfully prepared by immobilizing silver on the surface of zero-valent iron microspheres. Subsequent molecular imprinting on the bimetallic magnetic silver microspheres ensured selective removal and detection. The substrate exhibited magnetization saturation of 8.89 emu/g providing efficient analyte separation. It showed high sensitivity and selectivity toward carbaryl detection to nanomolar concentration level. Linear regression models for peaks at Raman shift 1599 cm and 2233 cm demonstrated a good linear fit with R=0.9738 and R=0.8952 respectively. The composite was successfully applied on spiked water samples resulting in average recovery rate of 89%. The findings of this study demonstrate great substrate potential for application in separation and detection of trace quantities of chemical contaminants for environment safety and protection.
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http://dx.doi.org/10.1080/03601234.2020.1869476DOI Listing
May 2021

Dummy molecular imprinted polymers coated with silver microspheres via surface enhanced Raman scattering for sensitive detection of benzimidazole.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Mar 14;249:119321. Epub 2020 Dec 14.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, State Key Lab of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

Dummy molecular imprinted polymers (MIPs) with carbendazim as a dummy template coated with Ag microspheres were fabricated in N, N-dimethylformamide solution via a surface-enhanced Raman scattering (SERS) enhancement for detection of benzimidazole by using methylacrylamide and ethylene glycol dimethacrylate as the functional monomer and cross-linker, respectively. The scanning electron microscope, transmission electron microscope, energy dispersive spectrometer, particle size distribution analysis, and X-ray diffraction were used to perform the morphology, size, and crystal structure for prepared [email protected] MIPs. Under the optimal conditions, the SERS detection method presented good linearity with concentrations in the range of 1.0 × 10 ~ 1.0 × 10 mol L for benzimidazole at 774 cm and 1004 cm, respectively. And the minimum detection concentration of this method was as low as 1.0 × 10 mol L. Besides, [email protected] MIPs exhibited satisfactory sensitivity and selectivity to benzimidazole instead of carbendazim due to the dummy imprinting technology to eliminate the background noise interference. The reusability result of [email protected] MIPs was shown that the characteristic peaks of benzimidazole are still obvious after four times of repeated detection. This method provided an effective way to develop a qualitative and semi-quantitative analysis of benzimidazole in complex matrices.
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http://dx.doi.org/10.1016/j.saa.2020.119321DOI Listing
March 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

Inhibition of EZH2 ameliorates bacteria-induced liver injury by repressing RUNX1 in dendritic cells.

Cell Death Dis 2020 12 1;11(11):1024. Epub 2020 Dec 1.

Department of Oncology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Fulminant hepatic failure (FHF) is a clinical syndrome characterized by a sudden and severe impairment in liver function. However, the precise mechanism of immune dysregulation that is significant to FHF pathogenesis remains unclear. Enhancer of zeste homolog 2 (EZH2) has been implicated in inflammation as a regulator of immune cell function. In this study, we investigated the role of EZH2 in an animal model of human FHF induced by Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS). We demonstrated that EZH2 depletion in dendritic cells (DCs) and pharmacological inhibition of EZH2 using GSK126 both significantly ameliorated liver injury and improved the survival rates of mice with P. acnes plus LPS-induced FHF, which could be attributed to the decreased infiltration and activation of CD4 T cells in the liver, inhibition of T helper 1 cells and induction of regulatory T cells. The expression of EZH2 in DCs was increased after P. acnes administration, and EZH2 deficiency in DCs suppressed DC maturation and prevented DCs from efficiently stimulating CD4 T-cell proliferation. Further mechanistic analyses indicated that EZH2 deficiency directly increased the expression of the transcription factor RUNX1 and thereby suppressed the immune functions of DCs. The functional dependence of EZH2 on RUNX1 was further illustrated in DC-specific Ezh2-deficient mice. Taken together, our findings establish that EZH2 exhibits anti-inflammatory effects through inhibition of RUNX1 to regulate DC functions and that inhibition of EZH2 alleviates P. acnes plus LPS-induced FHF, probably by inhibiting DC-induced adaptive immune responses. These results highlight the effect of EZH2 on DCs, serving as a guide for the development of a promising immunotherapeutic strategy for FHF.
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http://dx.doi.org/10.1038/s41419-020-03219-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708645PMC
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

The long noncoding RNA HCG18 participates in PM2.5-mediated vascular endothelial barrier dysfunction.

Aging (Albany NY) 2020 11 16;12(23):23960-23973. Epub 2020 Nov 16.

GMU-GIBH Joint School of Life Sciences, Center of Reproductive Medicine, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510182, China.

Increased vascular endothelial permeability can disrupt vascular barrier function and further lead to multiple human diseases. Our previous reports indicated that particulate matter 2.5 (PM2.5) can enhance the permeability of vascular endothelial cells. However, the regulatory mechanism was not comprehensively demonstrated. Therefore, this work elucidated this mechanism by demonstrating that PM2.5 can increase the permeability of HUVECs by inhibiting the expression of Hickson compact group 18 (HCG18). Moreover, we demonstrated that lncRNA HCG18 functioned as a ceRNA for miR-21-5p and led to the derepression of its target SOX7, which could further transcriptionally activate the expression of VE-cadherin to regulate the permeability of HUVECs. In this study, we provide evidence that HCG18/miR-21-5p/SOX7/VE-cadherin signaling is involved in PM2.5-induced vascular endothelial barrier dysfunction.
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http://dx.doi.org/10.18632/aging.104073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762519PMC
November 2020

Flower-like Ag coated with molecularly imprinted polymers as a surface-enhanced Raman scattering substrate for the sensitive and selective detection of glibenclamide.

Authors:
Xiaohui Ren Xin Li

Anal Methods 2020 06;12(22):2858-2864

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China.

Flower-like Ag was formed by nanosheet self-assembly as a SERS-active substrate and was utilized for the preparation of flower-like [email protected] imprinted polymers (MIPs) as a surface-enhanced Raman scattering (SERS) sensor. Based on the combination of the molecular imprinting technique and SERS technology, the flower-like [email protected] with high sensitivity and excellent selectivity were used as SERS substrates for the detection of glibenclamide. The imprinted layer could effectively protect the flower-like Ag from oxidation and thereby may improve the stability of the SERS substrate. The intensities of the characteristic peaks obtained for the flower-like [email protected] were higher than that of flower-like Ag. By applying the flower-like [email protected] as an efficient and ultra-sensitive SERS platform, glibenclamide was quantitatively detected in trace concentrations as low as 1 ng mL-1. Furthermore, the SERS enhancement for the flower-like [email protected] was due to the synergetic effect between electromagnetic enhancement and chemical enhancement. We believe that this reliable method can open up new opportunities for practical chemosensor or biosensor applications.
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http://dx.doi.org/10.1039/d0ay00575dDOI Listing
June 2020

Simultaneous Determination of Urine Methotrexate, 7-Hydroxy Methotrexate, Deoxyaminopteroic Acid, and 7-Hydroxy Deoxyaminopteroic Acid by UHPLC-MS/MS in Patients Receiving High-dose Methotrexate Therapy.

Anal Sci 2020 Dec 14;36(12):1479-1486. Epub 2020 Aug 14.

Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University.

Nephrotoxicity, the most important toxicity in high-dose methotrexate (MTX) therapy, is partly caused by the formation of crystal deposits in the kidney due to poor water solubility of MTX and its metabolites 7-hydroxy methotrexate (7-OH MTX), deoxyaminopteroic acid (DAMPA) and 7-hydroxy deoxyaminopteroic acid (7-OH DAMPA). Plasma MTX level-guided urine alkalinization, leucovorin rescue and glucarpidase detoxification are common strategies to overcome MTX-related nephrotoxicity. However, overestimation is a problem for MTX analysis by immunoassays due to the cross-reactivity of MTX metabolites (7-OH MTX and DAMPA). An UHPLC-MS/MS method for the simultaneous determination of MTX, 7-OH MTX, DAMPA and 7-OH DAMPA in human urine was developed, validated and applied in clinical practice. Samples were treated by one-step protein precipitation and analyzed within 3 min. The calibration range was 0.02 to 4 μmol/L for MTX and DAMPA, and 0.1 to 20 μmol/L for 7-OH MTX and 7-OH DAMPA. For all analytes, the intra-day and inter-day bias and imprecision were -8.0 to 7.6 and <9.0%, the internal standard normalized recovery and matrix factor were 92.34 to 109.49 and <20.68%. The plasma MTX and 7-OH MTX levels increased with the urine drug levels, age, serum creatinine and alanine transaminase, but urine could not replace blood for MTX monitoring due to their poor correlation (R, 0.16 to 0.51). Dose-normalized urine and plasma MTX and 7-OH MTX levels were similar between different patient groups (urine pH <7 or ≥7). Due to the large inter-individual variance of the analytes levels in both plasma and urine, these findings should be treated with caution.
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http://dx.doi.org/10.2116/analsci.19P481DOI Listing
December 2020

Stabilizing Atomically Dispersed Catalytic Sites on Tellurium Nanosheets with Strong Metal-Support Interaction Boosts Photocatalysis.

Small 2020 Sep 5;16(35):e2002356. Epub 2020 Aug 5.

International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.

The utilization of appropriate supports for constructing single-atom-catalysts is of vital importance to achieve high catalytic performances, as the strong mutual interactions between the atomically dispersed metal atoms and supports significantly influence their electronic properties. Herein, it is reported that atomic cobalt species (ACS) anchored 2D tellurium nanosheets (Te NS) can act as a highly active single-atom cocatalyst for boosting photocatalytic H production and CO reduction reactions under visible light irradiation, wherein Te NS serves as the ideal support material to bridge the light absorbers and ACS catalytic sites for efficient electron transfer. X-ray absorption near-edge structure spectroscopy reveals that the ACS are built by a Co center coordinated with five CoO bonding, which are anchored on Te NS through one CoTe bonding. The strong mutual interaction between the Te NS and ACS alters the electronic structure of Te NS, inducing the introduction of intermediate energy states, which act as trap sites to accommodate the photogenerated electrons for promoting photocatalytic reactions. This work may inspire further capability in designing other Te-based single-atom-catalysts for highly efficient solar energy conversion.
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http://dx.doi.org/10.1002/smll.202002356DOI Listing
September 2020

Decipher the connections between proteins and phenotypes.

Biochim Biophys Acta Proteins Proteom 2020 11 22;1868(11):140503. Epub 2020 Jul 22.

Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. Electronic address:

As the outward-most representation of life, phenotype is the fundamental basis with which humans understand life and disease. But with the advent of molecular and sequencing technique and research, a growing portion of science research focuses primarily on the molecular level of life. Our understanding in molecular variations and mechanisms can only be fully utilized when they are translated into the phenotypic level. In this study, we constructed similarity network for phenotype ontology, and then applied network analysis methods to discover phenotype/disease clusters. Then, we used machine learning models to predict protein-phenotype associations. Each protein was characterized by the functional profiles of its interaction neighbors on the protein-protein interaction network. Our methods can not only predict protein-phenotype associations, but also reveal the underlying mechanisms from protein to phenotype.
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http://dx.doi.org/10.1016/j.bbapap.2020.140503DOI Listing
November 2020

Histological transformation of lung adenocarcinoma to small cell lung cancer with mutant C797S conferring acquired resistance to osimertinib.

J Int Med Res 2020 Jun;48(6):300060520927918

Second Department of Respiratory Medicine, Shanxi Provincial Cancer Hospital, TaiYuan, ShanXi, P.R. China.

Epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer may initially respond to EGFR tyrosine kinase inhibitors (TKIs), but may subsequently become resistant; however, the resistance mechanisms remain unclear. We report a rare case of acquired resistance to osimertinib associated with transformation to small cell lung cancer (SCLC) with cis-C797S mutation. A man with recurrent lung adenocarcinoma harboring an exon 19 deletion received erlotinib for 10 months following curative surgery and adjuvant chemotherapy. However, he switched to osimertinib after repeat biopsy showed exon 19 deletion and T790M mutation leading to erlotinib resistance. His disease progressed after 15 months and repeat biopsy showed SCLC. Next-generation sequencing of peripheral blood detected exon 19 deletion, T790M mutation, cis-C797S mutation, and inactivation. The tumor was reduced after four cycles of etoposide and cisplatin and his respiratory symptoms improved. However, computed tomography after six cycles of chemotherapy showed multiple bilateral lung lesions, and single-photon emission computed tomography showed bone metastasis. The patient received paclitaxel plus cisplatin for two cycles with partial response. Because heterogeneous genetic and phenotypic mechanisms of TKI-resistance may occur at different times and locations, histopathological and molecular testing both provide evidence to support appropriate treatment.
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http://dx.doi.org/10.1177/0300060520927918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328482PMC
June 2020

Social Capital as a Mediator through the Effect of Education on Depression and Obesity among the Elderly in China.

Authors:
Yu Xin Xiaohui Ren

Int J Environ Res Public Health 2020 06 4;17(11). Epub 2020 Jun 4.

West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.

Objectives: Global aging is an increasingly serious problem. The health problems faced by the elderly, such as depression and obesity, require serious consideration. Education, depression and obesity are inextricably linked; for the elderly, education is constant, and the factors which can mediate the relationship between education, depression and obesity are still being discussed by scholars. The mediating effect of social capital is rarely studied. The objective of this study was to assess the mediating role of cognitive social capital and structural social capital, as well as the effect of education on depression and obesity among the elderly using China Family Panel Studies (CFPS) data.

Methods: In total, 4919 respondents were included in the final analysis. Education was measured by years of schooling. Trust and participation were used as measures of cognitive social capital and structural social capital. Depression symptoms and BMI were used as outcomes. Structural equation models were developed to examine the direct and indirect effect of social capital and education on health outcomes.

Results: Education was negatively correlated with depression symptom (r = -0.15, < 0.001), while education was positively correlated with BMI (r = 0.08, < 0.001). Older adults with a higher education level have higher cognitive social capital (r = 0.11, < 0.001) and structural social capital (r = 0.20, < 0.001). Social capital plays a mediatory role. Older adults with higher social capital have a lower risk of depression (cognitive: r = -0.23, < 0.001; structural: r = -0.03, < 0.01) but a higher risk of obesity (cognitive: r = 0.06, < 0.01; structural: r = 0.03, < 0.01). For depression, the mediating function of cognitive social capital (a1b1= -0.025) is stronger than that of structural social capital (a2b2 = -0.006). While, for obesity, the effects of both cognitive and structural social capital are the same (a1c1 = a2c2 = 0.005).

Conclusions: Social capital as a mediator through the effect of education on depression and obesity among the elderly in China. Meanwhile, using the positive effects of social capital to avoid negative effects should also be seriously considered.
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http://dx.doi.org/10.3390/ijerph17113977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312359PMC
June 2020

Association between obesity status and successful aging among older people in China: evidence from CHARLS.

BMC Public Health 2020 May 24;20(1):767. Epub 2020 May 24.

West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, No.17 Section 3, Renmin South Road, Chengdu, 610041, Sichuan, China.

Background: The paper aimed to examine the association between obesity status and successful aging among elderly adults in China and further find gender differences in the effect of components of successful aging on obesity status.

Methods: The data came from the follow-up survey(2015) of China Health and Retirement Longitudinal Study (CHARLS) and 4019 dwellers age 60 and over are included. Obesity status were defined by the body mass index (BMI) according to Chinese criteria. Successful aging was defined following Rowe and Kahn's multidimensional model. Multivariable logistic regression was used to estimate the relationship between obesity status and successful aging.

Results: The rate of successful aging in men and women was 18.87 and 9.48% respectively. For BMI, the proportion of population with underweight, overweight and obesity in men was 10.29, 23.04 and 29.63% respectively and that in women was 1.40, 11.69 and 9.47%. Men with obesity (OR = 1.587 95% CI 1.087 ~ 2.316) has an positive relationship with successful aging than normal weight men; Women with underweight (OR = 0.197 95% CI 0.058 ~ 0.824) has an negative relationship with successful aging than normal weight women; Meanwhile, no matter men and women, the relationship between obesity status and successful aging were not significant among oldest adults(≥75 years).

Conclusion: Obesity status was significantly association with successful aging in young older adults (60-74 years), and the components of successful aging differently were related with the obesity status of male and female.
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http://dx.doi.org/10.1186/s12889-020-08899-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245862PMC
May 2020

Postoperative delayed trapped temporal horn in patients with lateral ventricular trigone meningioma: Risk factors, surgical management, and literature review.

Eur J Surg Oncol 2020 12 24;46(12):2324-2330. Epub 2020 Apr 24.

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

Object: To assess the risk factors for and surgical treatment of delayed trapped temporal horn (dTTH) in patients who had undergone removal of lateral ventricular trigone meningioma.

Method: Patients with lateral ventricular trigone meningioma treated at our institution from 2011 to 2015 were identified. Predictors for dTTH were determined using logistic regression. Literature review and pooled analysis were also conducted to evaluate the comparative effectiveness of surgical treatment for dTTH.

Results: A total of 110 cases were included in the analysis. Thirteen (11.8%) cases developed dTTH following surgery. Multivariable logistic regression demonstrated an association of longer operative duration with higher incidence of dTTH (OR, 1.34; 95% CI, 1.00-1.80; p = 0.049). As surgical duration prolonged from less than 3 hours to 5 hours or more, the incidence of dTTH increased in a consistent, linear fashion from 7.7% to 13.9% (p = 0.03). Six cases (46.2%, 6/13) of dTTH underwent surgical treatment for their life-threatening symptoms. Seven studies including 13 cases of dTTH in the literature were identified. Literature data, including the current series, revealed a total of 24 procedures were performed in 19 cases. Endoscopic fenestration trended toward fewer complications than shunt (7.7% vs 25.0%, p = 0.530). There were no significant differences in failure rates between the two groups (23.1% vs 25.0%, p = 1.000).

Conclusion: Patients with prolonged operative duration may be at higher risk of dTTH. Endoscopic fenestration is considered in preference to shunt placement, since it possesses equivalent success rates with fewer complications and avoids the need for a permanent implant.
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http://dx.doi.org/10.1016/j.ejso.2020.04.033DOI Listing
December 2020

The integration of molecular imprinting and surface-enhanced Raman scattering for highly sensitive detection of lysozyme biomarker aided by density functional theory.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Mar 9;228:117764. Epub 2019 Nov 9.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, State Key Lab of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

Surface-enhanced Raman scattering (SERS) is a powerful bioanalytical technique that opens opportunities for early disease diagnosis and treatment by detecting biomarkers. However, the low sensitivity, selectivity, and reproducibility in the bioanalytical SERS are the main obstacles for clinical use. Herein, we demonstrate a high sensitive and selective label-free lysozyme biomarker detection platform based on coupling of SERS with molecular imprinting technique. The hierarchical silver microspheres with dendritic structure are controllably fabricated by a wet-chemical self-assembly approach. Based on selection of surface-active regions by density functional theory (DFT) simulations, a thin MIPs film (thickness < 15 nm) is then grafted on Ag microsphere surface through surface imprinting. As a result, the final synthesized [email protected] hybrid exhibits as low as 5 ng mL detection limit for target lysozyme, and high selectivity and reproducibility. Intensive "hot spots" in [email protected] confirmed by Raman mapping give rise to the high-performance SERS. Meanwhile, DFT calculations are employed to investigate the SERS spectra and assist the assignment for the characteristic peaks of lysozyme. We believe that the present study provides a reliable and high-sensitive protocol for label-free protein biomarkers detection.
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http://dx.doi.org/10.1016/j.saa.2019.117764DOI Listing
March 2020

Hypothermia treatment ameliorated cyclin-dependent kinase 5-mediated inflammation in ischemic stroke and improved outcomes in ischemic stroke patients.

Clinics (Sao Paulo) 2019 21;74:e938. Epub 2019 Oct 21.

The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China.

Objectives: The inflammatory response is a key mechanism of neuronal damage and loss during acute ischemic stroke. Hypothermia has shown promise as a treatment for ischemic stroke. In this study, we investigated the molecular signaling pathways in ischemic stroke after hypothermia treatment.

Methods: Cyclin-dependent kinase 5 (CDK5) was overexpressed or silenced in cultured cells. Nuclear transcription factor-κB (NF-κB) activity was assessed by measurement of the luciferase reporter gene. An ischemic stroke model was established in Sprague-Dawley (SD) rats using the suture-occluded method. Animals were assigned to three groups: sham operation control, ischemic stroke, and ischemic stroke + hypothermia treatment groups. Interleukin 1β (IL-1β) levels in the culture supernatant and blood samples were assessed by ELISA. Protein expression was measured by Western blotting.

Results: In HEK293 cells and primary cortical neuronal cultures exposed to hypothermia, CDK5 overexpression was associated with increased IL-1β, caspase 1, and NF-κB levels. In both a murine model of stroke and in patients, increased IL-1β levels were observed after stroke, and hypothermia treatment was associated with lower IL-1β levels. Furthermore, hypothermia-treated patients showed significant improvement in neurophysiological functional outcome.

Conclusions: Overall, hypothermia offers clinical benefit, most likely through its effects on the inflammatory response.
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http://dx.doi.org/10.6061/clinics/2019/e938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791290PMC
March 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
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