Publications by authors named "Xueyuan Wang"

57 Publications

Fluid and White Matter Suppression Imaging and Voxel-Based Morphometric Analysis in Conventional Magnetic Resonance Imaging-Negative Epilepsy.

Front Neurol 2021 29;12:651592. Epub 2021 Apr 29.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Delineation of subtle lesions in magnetic resonance imaging (MRI)-negative patients is of great importance in preoperative epilepsy evaluation. The aim of our study was to explore the diagnostic value of the novel fluid and white matter suppression (FLAWS) sequence in comparison with a voxel-based MRI postprocessing morphometric analysis program (MAP) in a consecutive cohort of non-lesional patients. Surgical candidates with a negative finding on an official neuroradiology report were enrolled. High-resolution FLAWS image and MAP maps generated based on high-resolution three-dimensional (3D) T1 image were visually inspected for each patient. The findings of FLAWS or MAP-positive (FLAWS/MAP+) regions were compared with the surgical resection cavity in correlation with surgical outcome and pathology. Forty-five patients were enrolled; the pathological examination revealed focal cortical dysplasia (FCD) in 32 patients and other findings in 13 patients. The positive rate, sensitivity, and specificity were 48.9%, 0.43, and 0.87, respectively, for FLAWS and 64.4%, 0.57, and 0.8, respectively, for MAP. Concordance between surgical resection and FLAWS+ or MAP+ regions was significantly associated with a seizure-free outcome (FLAWS: = 0.002; MAP: = 0.0003). A positive finding in FLAWS and MAP together with abnormalities in the same gyrus (FLAWS-MAP gyral+) was detected in 31.1% of patients. FLAWS+ only and MAP+ only were found in 7 (15.5%) and 14 (31.1%) patients, respectively. FLAWS showed a promising value for identifying subtle epileptogenic lesions and can be used as a complement to current MAP in patients with MRI-negative epilepsy.
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http://dx.doi.org/10.3389/fneur.2021.651592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116947PMC
April 2021

Discovery of novel tripeptide propylene oxide proteasome inhibitors for the treatment of multiple myeloma.

Bioorg Med Chem 2021 Jun 1;40:116182. Epub 2021 May 1.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China; Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd., No. 9 Weidi Road, Nanjing 210046, PR China. Electronic address:

The ubiquitin proteasome pathway (UPP) plays a critical role in the maintenance of cell homeostasis and the development of diseases, such as cancer and neurodegenerative disease. A series of novel tripeptide propylene oxide compounds as proteasome inhibitors were designed, synthesized and biologically investigated in this manuscript. The enzymatic activities of final compounds against 20S human proteasome were investigated and structure-activity relationship (SAR) was summarized. Some potent compounds were further evaluated to inhibit the proliferation of multiple myeloma (MM) cancer cell lines RPMI8226 and U266B. The results showed that some compounds were active against MM cancer cell lines with IC values of less than 50 nM. The microsomal metabolic stabilities in human, rat and mice species were carried out and the results showed that compounds 30 and 31 were stable enough to be in vivo investigated. The in vivo pharmacokinetic results showed that compounds 30 and 31 had acceptable biological parameters for both ig and iv administrations. In vivo antitumor activities of compounds 30 and 31 with the doses of 100 mg/kg and 50 mg/kg BIW were performed by using RPMI8226 xenograft nude mouse model. Toxicities of compounds 30 and 31 were not observed during the experiment and dose dependent effect was obvious and the tumor volume was greatly inhibited.
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http://dx.doi.org/10.1016/j.bmc.2021.116182DOI Listing
June 2021

Altered ripple density inside seizure onset zone in patients with focal cortical dysplasia-associated epilepsy.

Brain Behav 2021 May 7:e02169. Epub 2021 May 7.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Purpose: To evaluate the clinical and stereoelectroencephalography (SEEG) features and postsurgical outcome in a uniform series of patients who underwent epilepsy surgery and had pathologically confirmation of focal cortical dysplasia (FCD).

Methods: We studied consecutive patients with drug-refractory epilepsy who underwent SEEG recording. The high-frequency oscillations (HFOs) features of SEEG, clinical characteristics, and surgical outcome were evaluated.

Results: Sixty patients (31 FCD type I, 13 II, and 16 III) were analyzed retrospectively. Patients with type II tended to have their seizures at an earlier age than those with I and III (p < .01). Six different ictal onset patterns (IOPs) were identified. In patients with temporal lobe epilepsy (TLE), the most common patterns were rhythmic spikes or spike waves and LFRS, and in patients with extratemporal epilepsy, the most common patterns were low-voltage fast activity (LVFA) and rhythmic spikes or spike waves. In addition, ripple density was found to increase significantly from the interictal to ictal onset sections and from the ictal onset to ictal evolution sections in patients with FCD I (p < .001). Regarding the distinct IOPs, ripple density continued to increase significantly between the interictal and ictal onset sections in LVFA, rhythmic spikes or spike waves, and burst of high-amplitude polyspikes (p < .05). Ripple density decreased between ictal onset and ictal evolution sections in patterns of LVFA and rhythmic spikes or spike waves (p < .05). The mean follow-up duration was 2.7 years (range 1-4.2), and 66.7% (n = 40) were class I. Patients with subtypes III and II had favorable surgical outcome than those with I.

Conclusion: The clinical expression of seizure may depend on the pathological types with FCD II patients exhibiting their seizures at an earlier age. Distinct IOPs may demonstrate different ripple features and distinguishing the IOPs is very necessary to have an insight into the electrophysiological characteristics.
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http://dx.doi.org/10.1002/brb3.2169DOI Listing
May 2021

Anti-tumor activity of a novel proteasome inhibitor D395 against multiple myeloma and its lower cardiotoxicity compared with carfilzomib.

Cell Death Dis 2021 Apr 30;12(5):429. Epub 2021 Apr 30.

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China.

Carfilzomib, a second-generation proteasome inhibitor, has significantly improved the survival rate of multiple myeloma (MM) patients, but its clinical application is still restricted by drug resistance and cardiotoxicity. Here, we identified a novel proteasome inhibitor, D395, and assessed its efficacy in treating MM as well as its cardiotoxicity at the preclinical level. The activities of purified and intracellular proteasomes were measured to determine the effect of D395 on the proteasome. CCK-8 and flow cytometry experiments were designed to evaluate the effects of D395 on cell growth and apoptosis. The effects of D395 and carfilzomib on serum enzyme activity, echocardiography features, cardiomyocyte morphology, and hERG channels were also compared. In our study, D395 was highly cytotoxic to MM cell lines and primary MM cells but not normal cells, and it was well tolerated in vivo. Similar to carfilzomib, D395 inhibited osteoclast differentiation in a dose-dependent manner. In particular, D395 exhibited lower cardiotoxicity than carfilzomib in all experiments. In conclusion, D395 is a novel irreversible proteasome inhibitor that has remarkable anti-MM activity and mild cardiotoxicity in vitro and in vivo.
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http://dx.doi.org/10.1038/s41419-021-03701-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087809PMC
April 2021

Discovery of novel pyrimidine molecules containing boronic acid as VCP/p97 Inhibitors.

Bioorg Med Chem 2021 May 23;38:116114. Epub 2021 Mar 23.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China. Electronic address:

Valine-containing protein (VCP) is a member of the adenosine triphosphate family involved in a variety of cellular activities. VCP/p97 is capable of maintaining protein homeostasis and mediating the degradation of misfolded polypeptides by the ubiquitin-proteasome system (UPS). In this manuscript, a series of novel p97 inhibitors with pyrimidine as core structure were designed, synthesized and biologically evaluated. Based on the enzymatic results, a detailed structure-activity relationship discussion of the synthesized compounds was carried out. Furthermore, cellular activities of the compounds with enzymatic potency of less than 200 nM were investigated by using A549 and RPMI8226 cell lines. Among the screened inhibitors, compound 17 (IC, 54.7 nM) showed good enzymatic activity. Investigation of cellular activities with non-small cell lung cancer A549 and multiple myeloma (MM) RPMI8226 further confirmed the potency of 17 with the IC values of 2.80 μM and 0.86 μM, respectively. Compound 17 is now being developed as a candidate. Finally, docking studies were carried out to explore the possible binding mode between the active inhibitor 17 and p97.
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http://dx.doi.org/10.1016/j.bmc.2021.116114DOI Listing
May 2021

Functional characteristics of the human primary somatosensory cortex: An electrostimulation study.

Epilepsy Behav 2021 05 24;118:107920. Epub 2021 Mar 24.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing 100053, China.

The common knowledge of the functional organization of the human primary somatosensory cortex (S1) had been primarily established by Penfield who electrically stimulated the exposed surface [referred as Brodmann area (BA)1] of S1 under neurosurgical conditions. Nevertheless, the functional information regarding the deep surface (BA 2 and 3) of S1 is poorly understood. We retrospectively analyzed all the clinical manifestations induced by extra-operative cortical electrical stimulation (ES) in 33 patients with medically intractable epilepsy who underwent stereo-electroencephalography (SEEG) monitoring for presurgical assessment. Demographic and clinical data were gathered and evaluated to delineate the determinants of the occurrence of positive responses, types of responses, and size of body regions involved. The stimulation of 244 sites in S1 yielded 198 positive sites (81.1%), most of which were located in the sulcal cortex. In multivariable analyses, no clinical or demographic factors predicted the occurrence of responses or their threshold levels. The size of body region involved in the responses had ordinal association with the stimulated BA sites (p < 0.001). Various types of responses elicited from the S1 were documented and classified, and the predictors of those responses were also assessed. Our analysis revealed the functional characteristics of the entire S1 and proved the multiplicity of functions of S1.
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http://dx.doi.org/10.1016/j.yebeh.2021.107920DOI Listing
May 2021

The thalamus-precentral gyrus functional connectivity changes in epilepsy patients following vagal nerve stimulation.

Neurosci Lett 2021 04 9;751:135815. Epub 2021 Mar 9.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. Electronic address:

Vagal nerve stimulation (VNS) is an effective treatment for patients with drug-resistant epilepsy who are unsuitable for surgical epilepsy treatment. However, the mechanism of action of VNS remains unclear, and the efficacy of VNS treatment regarding seizure frequency reduction cannot be assessed before surgery. This study measured changes in functional connectivity between thalamus and precentral gyrus which are activated as vital targets of deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS) using resting-state functional MRI to evaluate the effects of VNS. 16 epilepsy patients who underwent VNS were collected and scanned by resting-state functional MRI before and after operation. The functional connections (regions of interest: thalamus, precentral gyrus) were examined. After three months of stimulation, there were eight responders (≥50 % seizure reduction) and eight non-responders to VNS. No significant difference in thalamus-precentral gyrus functional connectivity was found between responders and nonresponders before operation. Enhanced functional connections were observed between bilateral thalamus and bilateral precentral gyrus in responders, which decreased in nonresponders, while functional connections between bilateral thalamus decreased in both responders and nonresponders. Short-term stimulation may cause thalamus-precentral gyrus functional connectivity changes in DRE patients, and control seizures by enhancing functional connections between bilateral thalamus and bilateral precentral gyrus.
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http://dx.doi.org/10.1016/j.neulet.2021.135815DOI Listing
April 2021

Voxel-based morphometric MRI post-processing and PET/MRI co-registration reveal subtle abnormalities in cingulate epilepsy.

Epilepsy Res 2021 Mar 8;171:106568. Epub 2021 Feb 8.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. Electronic address:

Objective: Diagnostic challenges exist in the presurgical evaluation of patients with magnetic resonance imaging (MRI) negative cingulate epilepsy (CE) because of the heterogeneity in clinical semiology and lack of localizing findings on scalp electroencephalographic (EEG) recordings. We aimed to examine the neuroimaging characteristics in a consecutive cohort of patients with MRI-negative CE with a focus on two image post-processing methods, including the MRI post-processing morphometric analysis program (MAP) and F-fluorodeoxyglucose-positron emission tomography-MRI (PET/MRI) co-registration.

Methods: Included in this retrospective study were patients with MRI-negative CE who met the following criteria: negative on preoperative MRI, invasive EEG (iEEG) confirmed cingulate gyrus-onset seizures, surgical resection of the cingulate gyrus with/without adjacent cortex, and seizure-free for more than 12 months. MAP and PET/MRI co-registration were performed and investigated by comparison to ictal intracranial EEG findings. Other characteristics obtained from scalp EEG, magnetoencephalography (MEG), iEEG, and pathological study were also reported.

Results: Ten patients were included, of which eight were diagnosed with anterior CE, one with middle CE, and one with posterior CE. The semiology included fear, embarrassment, vocalization, ictal pouting, asymmetric tonic posture, hypermotor, and automatism. Scalp EEG revealed unilateral or bilateral frontal-temporal onset. MEG localized the dipoles correctly in one patient (1/10). MAP detected subtle abnormalities in regions concordant with iEEG onset in seven patients (7/10) while PET/MRI co-registration revealed focal concordant hypometabolism in five patients (5/10). Combining MAP with PET/MRI co-registration improved the detection rate to 90 % in this cohort. The pathology was focal cortical dysplasia (FCD), including FCD type IIA in three, type IIB in three, and type I in four.

Conclusion: MAP and PET/MRI co-registration show promising results in identifying subtle FCD abnormalities in CE with negative results on conventional MRI, which can be otherwise challenging. More importantly, a combination of MRI post-processing and PET/MRI co-registration can greatly improve the identification of epileptic abnormalities, which can be used as surgical target. MAP and PET/MRI co-registration should be incorporated into the routine presurgical evaluation.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106568DOI Listing
March 2021

Clinical application of intraoperative trial-free online-based language mapping for patients with refractory epilepsy.

Epilepsy Behav 2021 03 12;116:107496. Epub 2021 Feb 12.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Objective: The objective of the study was to develop and clinically test a trial-free online-based language mapping method for localizing the eloquent cortex easily in epilepsy operation.

Methods: Nine patients with refractory epilepsy were included in this study according to the results of preoperative evaluation for their epileptogenic zones (EZs) located adjacent to the eloquent cortex. When patients were awakened up from general anesthesia during operation, the trial-free online-based language-mapping paradigm was performed. All positive points marked on the cortex in each test were labeled and superimposed together as the result of functional mapping for each patient. The eloquent cortex was mapped according to the results obtained both from the intraoperative trial-free task localization method and the traditional electrical cortical stimulation (ECS).

Results: All patients completed this paradigms twice within 10 min. Based on the results of mapping, the EZs were tried to fully resected on the premise of preserving the mapped eloquent cortex as much as possible. The postoperative follow-up showed the outcome of Engel I in six patients and Engel II in three patients, whereas only two patients had aphemia after surgery and recovered within one week and three months, respectively.

Significance: The intraoperative trial-free online-based language mapping method was primarily identified to be safe and effective. This novel method seems to be promising and worthy of improvement.
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http://dx.doi.org/10.1016/j.yebeh.2020.107496DOI Listing
March 2021

and efficacy of the novel oral proteasome inhibitor NNU546 in multiple myeloma.

Aging (Albany NY) 2020 11 16;12(22):22949-22974. Epub 2020 Nov 16.

College of Life Science, Nanjing Normal University, Nanjing 210046, PR China.

Proteasome inhibition demonstrates highly effective impact on multiple myeloma (MM) treatment. Here, we aimed to examine anti-tumor efficiency and underlying mechanisms of a novel well tolerated orally applicable proteasome inhibitor NNU546 and its hydrolyzed pharmacologically active form NNU219. NNU219 showed more selective inhibition to proteasome catalytic subunits and less off-target effect than bortezomib . Moreover, intravenous and oral administration of either NNU219 or NNU546 led to more sustained pharmacodynamic inhibitions of proteasome activities compared with bortezomib. Importantly, NNU219 exhibited potential anti-MM activity in both MM cell lines and primary samples . The anti-MM activity of NNU219 was associated with induction of G2/M-phase arrest and apoptosis via activation of the caspase cascade and endoplasmic reticulum stress response. Significant growth-inhibitory effects of NNU219 and NNU546 were observed in 3 different human MM xenograft mouse models. Furthermore, such observation was even found in the presence of a bone marrow microenvironment. Taken together, these findings provided the basis for clinical trial of NNU546 to determine its potential as a candidate for MM treatment.
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http://dx.doi.org/10.18632/aging.104023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746380PMC
November 2020

Altered amplitude of low-frequency fluctuations and regional homogeneity in drug-resistant epilepsy patients with vagal nerve stimulators under different current intensity.

CNS Neurosci Ther 2021 Mar 23;27(3):320-329. Epub 2020 Sep 23.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: The mechanisms of vagal nerve stimulation (VNS) for the treatment of drug-resistant epilepsy (DRE) remain unclear. This study aimed to measure spontaneous brain activity changes caused by VNS in DRE patients using resting-state functional MRI (rs-fMRI).

Methods: The rs-fMRI scans were performed in 16 DRE patients who underwent VNS surgery. Amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) was generated and examined using paired sample t-test to compare activity changes at different current intensity stage. The preoperative and postoperative ALFF/ReHo were also compared in eight responders (≥50% reduction of seizure frequency three months after surgery) and eight nonresponders using paired sample t-test.

Results: The significant ALFF and ReHo changes were shown in various cortical/subcortical structures in patients under different current intensity. After three months of stimulation, responders exhibited increased ALFF in the right middle cingulate gyrus, left parahippocampal gyrus, and left cerebellum, and increased ReHo in the right postcentral gyrus, left precuneus, left postcentral gyrus, right superior parietal gyrus, right precentral gyrus, and right superior frontal gyrus. Nonresponders exhibited decreased ALFF in the left temporal lobe and right cerebellum, increased ALFF in bilateral brainstem, decreased ReHo in bilateral lingual gyri, and increased ReHo in the right middle frontal gyrus and right anterior cingulate gyrus.

Conclusions: The spontaneous neural activity changes in DRE patients caused by VNS were in an ongoing process. Increased ALFF/ReHo in frontal cortex, cingulate gyri, precentral/postcentral gyri, parahippocampal gyri, precuneus, parietal cortex, and cerebellum may implicate in VNS-induced improvement in seizure frequency.
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http://dx.doi.org/10.1111/cns.13449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871792PMC
March 2021

The functional connectivity study on the brainstem-cortical/subcortical structures in responders following cervical vagus nerve stimulation.

Int J Dev Neurosci 2020 Dec 14;80(8):679-686. Epub 2020 Oct 14.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: Cervical vagus nerve stimulation (VNS) is an effective neuromodulation therapy for patients with drug-resistant epilepsy (DRE). The previous studies reported that VNS may reduce seizures by regulating the functional connectivity (FC) between cortical and subcortical regions. However, no studies on brainstem have been done in responders who achieved ≥50% seizure reduction following VNS.

Methods: Eight healthy controls and eight patients who became responders after 3 months of operation were enrolled in this study. Resting-state functional MRI (rs-fMRI) was performed, and two sample and paired sample t test were, respectively, used to detect altered FC between brainstem and cortical/subcortical regions between controls and patients, between preoperative and postoperative patients.

Results: In the control group, regions with highest FC to brainstem included bilateral anterior cingulate gyri, left basal ganglia, left insula, left cuneus, right precuneus, and bilateral cerebellum. In preoperative patients, right frontal middle gyrus, bilateral basal ganglia, and right cerebellum were showed highest FC to brainstem. Compared with the controls, preoperative patients exhibited increased FC in bilateral inferior frontal gyri, right temporal cortex, while decreased FC in left insula, left postcentral gyrus, right posterior cingulate gyrus, right precuneus, and left superior parietal gyrus. In postoperative patients, regions with increased FC to brainstem were left insula, left precuneus and left cuneus, and those with decreased FC were right inferior occipital gyrus and right cerebellum.

Conclusions: Recurrent seizures caused disturbances in brainstem-cortical/subcortical FC, especially in motor executive function related regions and default mode network. VNS could reorganize the altered FC between brainstem and insula, precuneus, and cerebellum in responders.
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http://dx.doi.org/10.1002/jdn.10064DOI Listing
December 2020

The effect of vagal nerve stimulation on hippocampal-thalamic functional connectivity in epilepsy patients.

Brain Res Bull 2020 10 31;163:143-149. Epub 2020 Jul 31.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. Electronic address:

Background: Vagal nerve stimulation (VNS) is widely used as an auxiliary treatment for patients with intractable epilepsy. Up to now, the therapeutic mechanisms remain elusive, and no surgical prediction criteria has been proposed.

Methods: In this study, the resting-state functional magnetic resonance imaging (rs-fMRI) was chosen to explore aberrant intrinsic brain activity and functional connections in 14 epilepsy patients with VNS stimulators between March 2019 and April 2019. Seven patients who ≥ 50 % seizure reduction was defined as responders, and seven non-responders. All patients had got rs-fMRI scan before and after operation. The hippocampal - thalamic connections (hippocampal and thalamus as regions of interest) were detected to evaluate the diversity in all 14 patients and seven responders with stimulation at 0, 0.5, 1.0, and 1.5 mA. The hippocampal-thalamic connections before operation were also examined between responders and non-responders.

Results: The preoperative left hippocampal - left thalamic connections and left hippocampal - right thalamic connections in responders were lower than those in non-responders (p < 0.05). While, there was no significant difference in hippocampal - thalamic connections in all epilepsy patients or responders with different current intensities (p > 0.05).

Conclusions: VNS may be more suitable for patients with lower left hippocampal - left thalamic connections and/or left hippocampal - right thalamic connections. The current intensity ≤ 1.5 mA and stimulation time ≤ 3 months may not cause significant changes in hippocampal-thalamic functional connectivity.
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http://dx.doi.org/10.1016/j.brainresbull.2020.07.023DOI Listing
October 2020

Epilepsy duration as an independent predictor of response to vagus nerve stimulation.

Epilepsy Res 2020 11 17;167:106432. Epub 2020 Jul 17.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, PR China. Electronic address:

Background: Vagus nerve stimulation (VNS) is a form of neuromodulation that has been used to treat individuals with drug-resistant epilepsy (DRE). Although many retrospective studies have explored the predictors of VNS treatment efficacy, the data have been inconsistent, and no VNS studies to date have used the 2017 ILAE epilepsy classification system.

Methods: In this single-center retrospective study, we reviewed data from 77 patients who underwent VNS implantation between 2011 and 2019. Data regarding patient gender, epilepsy duration, age at implantation, numbers of antiepileptic drugs, MRI findings, history of craniotomy, epilepsy classification, stimulation current intensity, stimulation duration, and responder status (responders were those with ≥ 50 % seizure frequency reduction) were analyzed via univariate analysis or receiver operating characteristic (ROC) curves to select possible related factors and classification cutoffs. Then, binary logistic regression analysis was used to identify the variables that significantly predicted responder status.

Results: In the inclusion group, the mean stimulation duration, mean seizure reduction, and responder rate was 47.2 months, 42.6 %, and 50.6 %, respectively. The univariate analysis indicated that seizure types and MRI findings might be related categorical variables (P < 0.05). After performing binary logistic regression and creating ROC curves for the continuous variables, epilepsy duration was chosen as a related variable, with 12.5 years as the classification cutoff (P = 0.002). A binary logistic regression of risk factors showed that epilepsy duration was significantly related to responder status (P < 0.05).

Conclusion: Epilepsy duration is an independent predictor for responders to VNS. VNS is more likely to be efficacious in those with an epilepsy duration < 12.5 years, especially those with a duration of 5-12.5 years.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106432DOI Listing
November 2020

The changes in the topological properties of brain structural network based on diffusion tensor imaging in pediatric epilepsy patients with vagus nerve stimulators: A graph theoretical analysis.

Brain Dev 2021 Jan 24;43(1):97-105. Epub 2020 Jul 24.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. Electronic address:

Purpose: This study aimed to analyze the topological characteristics of brain structural network in pediatric epilepsy patients with vagus nerve stimulation (VNS) by applying graph theoretical approaches.

Methods: Nine patients with generalized seizures and eight normal controls (NC) were enrolled. Based on diffusion tensor imaging, graph theory analysis was used to characterize the topological properties in preoperative patients (EP-pre), postoperative patients (EP-post) and NC. The global properties included clustering coefficient (Cp), shortest path length (Lp), small-worldness (γ, λ, δ), global network efficiency (Eg) and local network efficiency (Eloc). The regional properties included degree centrality (DC), nodal efficiency (NE), nodal local efficiency (NLE) and nodal shortest path length (Np). Two sample t-test and paired sample t-test were utilized to compare properties difference.

Results: All three groups followed small-world characteristics. There was no significant difference in small-worldness, Cp, Lp, Eg or Eloc between EP-pre and EP-post. Compared with EP-pre: DC in EP-post decreased in the right cuneus and right temporal gyri, while increased in the right paracentral lobule; NE in EP-post decreased in the left dorsolateral superior frontal gyrus, right cuneus, right supramarginal gyrus, and right rolandic operculum, while increased in the right paracentral lobule; NLE in EP-post decreased in the left posterior cingulate gyrus and right supramarginal gyrus, while increased in the left parahippocampal gyrus; NP in EP-post decreased in the right paracentral lobule, while increased in the right cuneus.

Conclusion: VNS causes topological characteristics changes in pediatric patients with generalized seizures through regulating regional properties in some brain structures.
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http://dx.doi.org/10.1016/j.braindev.2020.07.006DOI Listing
January 2021

A resting-state functional MRI study on the effect of vagal nerve stimulation on spontaneous regional brain activity in drug-resistant epilepsy patients.

Behav Brain Res 2020 08 29;392:112709. Epub 2020 May 29.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. Electronic address:

Purpose: To explore the effect of vagal nerve stimulation (VNS) on spontaneous brain activity in patients with drug-resistant epilepsy (DRE).

Methods: 15 patients and eight healthy controls (HC) were enrolled and scanned by resting-state functional MRI to investigate changes in the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). A two-sample t-test or paired sample t-test was used to compare activity between the HCs, preoperative patients (EP-pre), and postoperative patients (EP-post). We also performed correlation analyses to examine the seizure improvement ratio.

Results: The voxel-level analyses indicated that, compared with the HC, the EP-pre group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral/postcentral gyrus, amygdala, insula, cerebellum, and lingual gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral gyrus, insula, anterior/median cingulate gyri, and cerebellum. The regions of interest-level analyses indicated that, compared with HC, the EP-pre group exhibited decreased fALFF or ReHo in the caudate nucleus, supramarginal gyrus, precuneus and middle temporal gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited increased fALFF or ReHo in the olfactory cortex, gyrus rectus, and superior temporal gyrus. Increased ReHo in the right superior or middle temporal gyrus was positively correlated with the improvement ratio.

Conclusions: Altered regional activity in DRE patients was reorganized after 3 months of stimulation. Increased ReHo in the right superior or middle temporal gyrus was implicated in VNS-induced improvement in seizure frequency.
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http://dx.doi.org/10.1016/j.bbr.2020.112709DOI Listing
August 2020

Subthalamic Nucleus Stimulation Modulates Motor Epileptic Activity in Humans.

Ann Neurol 2020 08 3;88(2):283-296. Epub 2020 Jun 3.

Department of Functional Neurosurgery, Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Objective: Pharmaco-refractory focal motor epileptic seizures pose a significant challenge. Deep brain stimulation (DBS) is a recently recognized therapeutic option for the treatment of refractory epilepsy. To identify the specific target for focal motor seizures, we evaluate the modulatory effects of the subthalamic nucleus (STN) stimulation because of the critical role of STN in cortico-subcortical motor processing.

Methods: Seven patients with epilepsy with refractory seizures who underwent chronic stereoelectroencephalography (SEEG) monitoring were studied in presurgical evaluation. Seizure onset zone was hypothesized to be partially involved in the motor areas in 6 patients. For each patient, one electrode was temporally implanted into the STN that was ipsilateral to the seizure onset zone. The cortical-subcortical seizure propagation was systemically evaluated. The simultaneously electrophysiological responses over distributed cortical areas to STN stimulation at varied frequencies were quantitatively assessed.

Results: We observed the consistent downstream propagation of seizures from the motor cortex toward the ipsilateral STN and remarkable cortical responses on motor cortex to single-pulse STN stimulation. Furthermore, we showed frequency-dependent upstream modulatory effect of STN stimulation on motor cortex specifically. In contrast to the enhanced effects of low frequency stimulation, high-frequency stimulation of the STN can significantly reduce interictal spikes, high-frequency oscillations over motor cortex disclosing effective connections to the STN.

Interpretation: This result showed that the STN is not only engaged in as a propagation network of focal motor seizures but STN stimulation can profoundly modulate the epileptic activity of motor cortex in humans, suggesting a mechanism-based alternative for patients suffering from refractory focal motor seizures. ANN NEUROL 2020;88:283-296.
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http://dx.doi.org/10.1002/ana.25776DOI Listing
August 2020

The value of magnetoencephalography for stereo-EEG-guided radiofrequency thermocoagulation in MRI-negative epilepsy.

Epilepsy Res 2020 07 20;163:106322. Epub 2020 Mar 20.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. Electronic address:

Objective: Magnetoencephalography (MEG) is valuable for guiding resective surgery in patients with epilepsy. However, its value for minimally invasive treatment is still unknown. This study aims to evaluate the value of MEG for stereo-electroencephalogram (EEG)-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) in magnetic resonance imaging (MRI)-negative epilepsies.

Methods: An observational cohort study was performed and 19 MRI-negative patients who underwent SEEG-guided RF-TC in our epilepsy center were included. In addition, 16 MRI-positive patients were included as a reference group. Semiology, electrophysiology, and imaging information were collected. To evaluate the value of locating the MEG cluster, the proportion of the RF-TC contacts located in the MEG cluster out of all contacts used to perform RF-TC in each patient was calculated. All patients underwent the standard SEEG-guided RF-TC procedure and were followed up after the treatment.

Results: Nineteen MRI-negative patients were divided into two groups based on the existence of MEG clusters; 10 patients with MEG clusters were in group I and nine patients without any MEG cluster were in group II. No significant difference was observed in terms of age, sex, type of seizures, or number of SEEG electrodes implanted. The median of the proportion of contacts in the MEG cluster was 77.0 % (IQR 57.7-100.0 %). The follow-up results showed that the probability of being seizure-free at one year after RFTC in MRI-negative patients with an MEG cluster was 30.0 % (95 % CI 11.6-77.3 %), significantly (p = 0.014) higher than that in patients without an MEG cluster; there was no significant difference when compared with MRI-positive patients.

Conclusion: This is the first study to evaluate the value of MEG in SEEG-guided RF-TC in MRI-negative epilepsies. MEG is a useful supplement for patients with MRI-negative epilepsy. MEG can be applied in minimally invasive treatment. MEG clusters can help identify better candidates and provide a valuable target for SEEG-guided RF-TC, which leads to better outcomes.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106322DOI Listing
July 2020

Amygdalar and hippocampal beta rhythm synchrony during human fear memory retrieval.

Acta Neurochir (Wien) 2020 10 26;162(10):2499-2507. Epub 2020 Mar 26.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.

Background: Fear, as one of the basic emotions, is crucial in helping humans to perceive hazards and adapt to social activities. Clinically, fear memory is also involved in a wide spectrum of psychiatric disorders. A better understanding of the neural mechanisms of fear thereby has both neuroscientific and clinical significance. In recent years, data from animal models have demonstrated the key role of the amygdala-hippocampal circuit in the development of fear. However, the neural processing of fear memory remains unclear in humans, which is mainly due to the limitation of indirect measure of neural activity.

Methods: Herein, we investigated fear memory by direct intracranial recordings from 8 intractable epilepsy patients with depth electrodes in both the hippocampus and ipsilateral amygdala. All the patients were subjected to a well-established Pavlovian fear memory paradigm consisted of the familiarization task, conditioning task, and retrieval task, respectively. Simultaneous local field potentials from the hippocampus and amygdala were recorded during different stages. The oscillatory activities from the amygdala and hippocampus were analyzed during fear memory retrieval compared with neutral stages.

Results: Consistent with previous rodent studies, our results showed that the amygdala was involved in fear memory retrieval rather than neutral memory retrieval, while the hippocampus was involved both in fear memory retrieval and neutral memory retrieval. In particular, we found that there was an enhanced synchronized activity between the amygdala and hippocampus at beta frequencies (14-30 Hz), which suggested that enhanced synchronized activity at beta frequencies between the amygdala and hippocampus play a pivotal role during retrieval of fear memory in human.

Conclusions: Thus, our observation that the amygdala-hippocampal system contributing to fear memory retrieval in human with frequency-depended specificity has provided new insights into the mechanism of fear and have potential clinical relevance.
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http://dx.doi.org/10.1007/s00701-020-04276-yDOI Listing
October 2020

Long-term outcome of unilateral deep brain stimulation of the subthalamic nucleus for a patient with drug-resistant focal myoclonic seizure.

Ann Transl Med 2020 Jan;8(1):18

Department of Neurology, Comprehensive Epilepsy Center of Beijing, Beijing Key Laboratory of Neuromodulation, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

It remains an unsolved problem in the treatment of patients with refractory focal epilepsy originating from the motor cortex since resection surgery can result in significant morbidity. Neurostimulation has emerged as an effective method for treating patients who are not suitable for conventional surgical procedures due to its relative safety, reversibility, and lower risk of complications. The subthalamic nucleus (STN) has been shown to be a potential target for treating refractory motor seizures. Here, we report a favorable outcome of unilateral deep brain stimulation (DBS) of the STN for a patient with drug-resistant focal myoclonic seizures during a 5-year follow-up period.
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http://dx.doi.org/10.21037/atm.2019.12.43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995734PMC
January 2020

Reversible Hybrid Aqueous Li-CO Batteries with High Energy Density and Formic Acid Production.

ChemSusChem 2020 May 18;13(10):2621-2627. Epub 2020 Mar 18.

CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Provincial Key Laboratory of Nanomaterials, State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Yang Qiao West Road 155#, Fuzhou, 350002, P. R. China.

Metal-CO batteries, an attractive technology for both energy storage and CO utilization, are typically classified into organic Li(Na)-CO batteries with a high energy density/output voltage and aqueous Zn-CO batteries with flexible chemical production. However, achieving both high-efficiency energy storage and flexible chemical production is still challenging. In this study, a reversible hybrid aqueous Li-CO battery is developed, integrating Li with an aqueous phase, which exhibits not only a high operating voltage and energy density but also highly selective formic acid production. Based on a Li plate as the anode, NaCl solution as the aqueous electrolyte, solid electrolyte Li Al Ge P O (LAGP) as a separator and Li transporter, and a bifunctional Pd-based electrocatalyst as the cathode, the resulting battery shows a high discharge voltage of up to 2.6 V, an outstanding energy conversion efficiency of above 80 %, and remarkable selectivity of CO -to-HCOOH conversion of up to 97 %. The related reaction mechanism is proposed as CO +2 Li+2 H ⇌HCOOH+2 Li .
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http://dx.doi.org/10.1002/cssc.201903297DOI Listing
May 2020

Preparation and biological evaluation of soluble tetrapeptide epoxyketone proteasome inhibitors.

Bioorg Med Chem 2019 09 30;27(18):4151-4162. Epub 2019 Jul 30.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210046, PR China; Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd., No. 9 Weidi Road, Nanjing 210046, PR China. Electronic address:

A series of novel tetrapeptidyl epoxyketone inhibitors of 20S proteasome was designed and synthesized. To fully understand the SAR, various groups at R, R, R, R and R positions, including aromatic and aliphatic substituents were designed, synthesized and biologically assayed. Based on the enzymatic results, seven compounds were selected to evaluate their cellular activities and soluble compound 36 showed strong potency against human multiple myeloma (MM) cell lines. Microsomal stability results indicated that compound 36 was more stable in mice, rat and human microsomes than marketed carfilzomib. The in vivo activities of this compound were evaluated with the xenograft mice models of MM cell lines ARH77 and RPMI-8226 with luciferase expression and the T/C value of the two models were 49.5% and 37.6%, respectively. To evaluate the potential cardiovascular toxicity, inhibition of hERG ion channel in HEK293 cells by compound 36 and carfilzomib was carried out. The results indicated that 36 had no binding affinity for the hERG ion channel while carfilzomib could bind it with IC of 92.1 μM.
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http://dx.doi.org/10.1016/j.bmc.2019.07.044DOI Listing
September 2019

Pollution haven or porter? The impact of environmental regulation on location choices of pollution-intensive firms in China.

J Environ Manage 2019 Oct 13;248:109248. Epub 2019 Jul 13.

School of Economics, Zhejiang Gongshang University, 18 Xuezheng Road, Hangzhou, 310018, China. Electronic address:

Using firm establishment-level data combined with provincial socio-economic characteristic panel data in China for the period of 2011-2015, this study seeks to empirically examine the impact of environmental regulation on location choices of polluting firms. The results of the conditional logit model provide compelling evidence that environmental regulations do affect the location choice of firms in polluting industries. Instead of supporting the pollution haven effect, our results consistently confirm the Porter effect at the country level. This result is robust when taking endogeneity problem into account, adopting various model specifications and estimation strategies, using alternative measurements of environmental regulation and location choices, and subsampling excluding international political events. However, the results also show divergent effect of environmental regulation on location choices for heterogeneous firms. Specifically, polluting firms in eastern region prefer to invest in provinces with stringent environmental policies but those in other regions, especially in northeastern region, choose to locate in provinces with lax environmental regulation. While water-dependent polluting firms with a low level of footlooseness are more likely to enter locations with loose environmental regulation, air pollution-intensive firms tend to locate in provinces with tight environmental legislation. These results have policy implications for transitional China as well as other developing countries with similar experience.
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http://dx.doi.org/10.1016/j.jenvman.2019.07.019DOI Listing
October 2019

Pre-surgical Language Mapping in Epilepsy: Using fMRI in Chinese-Speaking Patients.

Front Hum Neurosci 2019 5;13:183. Epub 2019 Jun 5.

State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Accurate localization of language processing areas is critical in patients undergoing epilepsy surgery. In this study, we aimed to use functional magnetic resonance imaging (fMRI), which is a non-invasive mapping method, to establish a panel of tasks investigating patients' language function. We developed six tasks, including a series of progressive comprehension tasks from words, sentence to text, a verb generation task that can detect subtle left-brain activation, an auditory comprehension task that explored the temporal language-related areas, and a visual object-naming task provided for poorly educated patients. We successfully located the language cortex in 40 patients, and subsequently determined hemispheric dominance for the Chinese language. Our results showed a concordance between fMRI tasks and electrical cortical stimulation. The consistency across tasks revealed by the laterality index, as well as the concordance between the surgical outcomes and the results of localization, suggested the validity of our fMRI tasks. Our fMRI tasks also corroborate and extend the finding that the left middle frontal area (BA 9) plays an important role in reading Chinese.
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http://dx.doi.org/10.3389/fnhum.2019.00183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560162PMC
June 2019

Dual-functionalized liposome by co-delivery of paclitaxel with sorafenib for synergistic antitumor efficacy and reversion of multidrug resistance.

Drug Deliv 2019 Dec;26(1):262-272

b College of Life Science, Nanjing Normal University , Nanjing , PR China.

Multidrug resistance (MDR) remains one of the major reasons for inefficiency of many chemotherapeutic agents in cancer therapy. In this study, a D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and polylysine-deoxycholic acid copolymer (PLL-DA) co-modified cationic liposome coating with hyaluronic acid (HA) was constructed for co-delivery of paclitaxel (PTX) and chemosensitizing agent, sorafenib (SOR) to treat the MDR cancer. The multifunctional liposome (HA-TPD-CL-PTX/SOR) presented good stability against rat plasma and was capable of reversing surface zeta potential under acidic conditions in the presence of HAase. Additionally, experimental result confirmed that the PLL-DA copolymer would facilitate the endo-lysosomal escape of the liposome. In vitro study demonstrated that HA-TPD-CL-PTX/SOR could significantly enhance drug accumulation in resistant MCF-7/MDR cells by inhibiting the P-gp efflux, and effectively inhibited growth of tumor cells. Furthermore, the liposome showed an enhanced anticancer activity in vivo, with a tumor growth inhibition rate of 78.52%. In summary, HA-TPD-CL-PTX/SOR exhibited a great potential for effective therapy of resistant cancers by combining with chemotherapeutic agents and could be a promising nano-carrier for reversing MDR and improving the effectiveness of chemotherapy.
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http://dx.doi.org/10.1080/10717544.2019.1580797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419656PMC
December 2019

Rechargeable Zn-CO Electrochemical Cells Mimicking Two-Step Photosynthesis.

Adv Mater 2019 Apr 25;31(17):e1807807. Epub 2019 Feb 25.

Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Metal-CO batteries represent a promising priority for sustainable energy and the environment. However, CO utilization in nonaqueous electrolytes mostly involves difficult CO electrochemistry, leading to poor selectivity and limited cycle performance. Herein, an aqueous rechargeable Zn-CO electrochemical cell that tunably produced CO fuel gas (90% Faradaic efficiency) during cell discharge (cathodic reaction: CO + 2e + 2H → CO + H O) and O during cell charge at ≈2 V (cathodic reaction: H O → 1/2O + 2e + 2H ), mimicking the separate steps of CO fixation and water oxidation during photosynthesis while exhibiting the advantages of high efficiency, tunable products, and operation independent of sunlight is proposed and realized. The cell achieves a remarkable energy efficiency of 68% with fuel generation, providing an alternative for the green, efficient, and safe utilization of CO by metal-CO batteries.
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http://dx.doi.org/10.1002/adma.201807807DOI Listing
April 2019

Synthesis of water soluble pentacyclic dihydroxyterpene carboxylic acid derivatives coupled amino acids and their inhibition activities on α-glucosidase.

Bioorg Chem 2019 05 2;86:277-287. Epub 2019 Feb 2.

Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering Jiangxi Agricultural University, Nanchang 33045, China. Electronic address:

Twenty maslinic acid and corosolic acid derivatives were obtained by coupling with l-amino acids at C-28 position. The α-glucosidase inhibitory activities of the present compounds were evaluated in vitro. Results reveal that some of the derivatives exhibit a better α-glucosidase inhibitory activity than that of acarbose in the test conditions of ethanol-water solution and DMSO. It is worth noting that maslinic acid and corosolic acid derivatives coupled aspartic acid (9f: IC = 382 μm and 10f: IC = 364 μm, respectively) have the best water solubility and thus presented higher inhibitory activity than that of acarbose (IC = 484 μm). Unfortunately, all of the derivatives possess lower inhibitory properties of α-glucosidase than those of the parent compounds in the measurement system of DMSO solution, even if the derivatives exhibit better water solubility than that of the parent compounds.
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http://dx.doi.org/10.1016/j.bioorg.2019.02.001DOI Listing
May 2019

Discovery of a new class of valosine containing protein (VCP/P97) inhibitors for the treatment of non-small cell lung cancer.

Bioorg Med Chem 2019 02 28;27(3):533-544. Epub 2018 Dec 28.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China. Electronic address:

Valosine containing protein (VCP/p97) is a member of the AAA ATPase family involved in several essential cellular functions and plays an important role in the ubiquitin-mediated degradation of misfolded proteins. P97 has a significant role in maintaining the cellular protein homeostasis for tumor cell growth and survival and has been found overexpressed in many tumor types. No new molecule entities based on p97 target were approved in clinic. Herein, a series of novel pyrimidine structures as p97 inhibitors were designed and synthesized. After enzymatic evaluations, structure-activity relationships (SAR) were discussed in detailed. Among the screened compounds, derivative 35 showed excellent enzymatic inhibitory activity (IC, 36 nM). The cellular inhibition results showed that compound 35 had good antiproliferative activity against the non-small cell lung cancer A549 cells (IC, 1.61 μM). Liver microsome stability showed that the half-life of compound 35 in human liver microsome was 42.3 min, which was more stable than the control CB-5083 (25.8 min). The in vivo pharmacokinetic results showed that the elimination phase half-lives of compound 35 were 4.57 h for ig and 3.64 h for iv, respectively and the oral bioavailability was only 4.5%. These results indicated that compound 35 could be effective for intravenous treatment of non-small cell lung cancer.
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http://dx.doi.org/10.1016/j.bmc.2018.12.036DOI Listing
February 2019

Discovery of a novel dipeptidyl boronic acid proteasome inhibitor for the treatment of multiple myeloma and triple-negative breast cancer.

Org Biomol Chem 2019 01;17(3):683-691

College of Science, Nanjing Forestry University, No. 159 Longpan Road, Nanjing 210037, PR China.

A series of novel dipeptidyl boronic acid compounds were designed, synthesized and biologically investigated for the inhibition of the β5 subunit of 20S proteasome and several compounds showed high activities with IC50 values of less than 10 nM. Some of these compounds potently inhibited the multiple myeloma (MM) cancer cell lines with IC50 values of less than 10 nM. It was reported that the inhibition of both β2 and β5 subunits strongly increased the cytotoxicity of proteasome inhibitors in solid tumor cells, so some of the compounds were evaluated for the inhibition of the β2 subunit and the solid tumor triple-negative breast cancer cell line MDA-MB-231. The results showed that three compounds were active for both the β2 subunit and the triple-negative breast cancer cell line MDA-MB-231. The in vivo pharmacokinetic results showed that compound 8t had good biological parameters for both ig and iv administrations. An in vivo pharmacodynamic experiment showed that compound 8t inhibited the β5 subunit in whole blood more greatly than the marketed MLN9708 with the same dose at different time periods. A pathological analysis indicated that the injection of compound 8t in the tumor of a triple-negative breast cancer xenograft mice model led to tumor cell necrosis, nucleus condensation, deep staining, cell fragmentation, dissolution and neutrophil infiltration compared with the control group. The data in hand showed that compound 8t might be an effective candidate for the treatment of both MM and triple-negative breast cancer.
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http://dx.doi.org/10.1039/c8ob02668hDOI Listing
January 2019

Mirth and laughter induced by electrical stimulation of the posterior insula.

J Clin Neurosci 2019 Mar 27;61:269-271. Epub 2018 Nov 27.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.

Laughter induced in the insula is uncommon. In this case-report we present a description of a patient with drug-resistant focal epilepsy for whom laughter with mirth was elicited when the posterior insula (PI) was stimulated by intracranial electrodes. We attempted to analyze the progression of laughter in the insula and suggest a possible pathway for the expression of laughter.
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http://dx.doi.org/10.1016/j.jocn.2018.11.029DOI Listing
March 2019