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Glioma is the result of malignant transformation of glial cells in the white matter of the brain or spinal cord and accounts for approximately 80% of all intracranial malignancies. Cathepsin A (CTSA) is highly expressed in a variety of tumor tissues, but its role in glioma is poorly studied. This study analyses the relationship between CTSA, and glioma based on The Cancer Genome Atlas (TCGA).Data for glioma patients were collected from TCGA. The expression level of CTSA was compared between paired glioma tissues and normal tissues with Wilcoxon rank-sum test. In addition, the Wilcoxon ranksum test was also applied to analyze the relationship between clinicopathologic features and CTSA expression. Kaplan-Meier Plotter was applied to analyze OS, DSS and PFI. Immuno-infiltration analysis of BLCA was performed by single sample gene set enrichment analysis (ssGSEA) in the "GSVA" R package.The CTSA was overexpressed in glioma tissues compared to normal tissues (P0.001). The high expression of CTSA was significantly related to 1p/19q codeletion, IDH, WHO grade and histological type. Kaplan-Meier survival analysis showed that patients with glioma characterized with high expressed CTSA had a poorer OS (HR=2.16 P0.001), DSS (HR=2.17 P0.001) and PFI (HR=1.48 P0.001) than patients with low CTSA expression. Moreover, High expressed CTSA was associated with immune cell infiltration.CTSA may serve as a candidate prognostic biomarker for determining prognosis associated with immune infiltration in glioma.Gliom je rezultat maligne transformacije glijalnih ćelija u beloj materiji mozga ili kičmene moždine i čini približno 80% svih intrakranijalnih maligniteta. Katepsin A (CTSA) je visoko eksprimiran u različitim tumorskim tkivima, ali je njegova uloga u gliomu slabo pročavana. Ova studija analizira odnos između CTSA i glioma na osnovu The Cancer Genome Atlas (TCGA).Podaci za pacijente sa gliomom su prikupljeni od TCGA. Nivo ekspresije CTSA je upoređen između uparenih tkiva glioma i normalnih tkiva pomoću Wilcoxon testa rangsume. Pored toga, Wilcoxon rank-sum test je takođe primenjen za analizu odnosa između kliničkopatoloških karakteristika i ekspresije CTSA. Kaplan-Meier ploter je primenjen za analizu OS, DSS i PFI. Imuno-infiltraciona analiza BLCA izvršena je analizom obogaćivanja skupa gena jednog uzorka (ssGSEA) u paketu "GSVA" R.CTSA je bio prekomerno izražen u tkivima glioma u poređenju sa normalnim tkivima (P0,001). Visoka ekspresija CTSA bila je značajno povezana sa 1p/19k kodelecijom, IDH, VHO stepenom i histološkim tipom. Kaplan-Meierova analiza preživljavanja je pokazala da su pacijenti sa gliomom okarakterisanim visoko izraženim CTSA imali lošiji OS (HR=2,16 P0,001), DSS (HR=2,17 P0,001) i PFI (HR=1,48 P0,001) od pacijenata sa niska ekspresija CTSA. Štaviše, visoko izraženi CTSA je bio povezan sa infiltracijom imunih ćelija.CTSA može poslužiti kao kandidat za prognostički biomarker za određivanje prognoze povezane sa imunološkom infiltracijom u gliomu.

Glioma stem cells (GSCs) have potential for proliferation, self-renewal, and differentiation-the properties that play decisive roles in the process of malignancy in glioma. MicroRNAs (miRNAs) have been shown to regulate the characteristics of cancer stem cells. In this study, we show that miR-145-5p, a recently discovered miRNA, is expressed at low levels in primary GSCs (pGSCs). Upregulation of miR-145-5p resulted in the inhibition of proliferation and increased apoptosis of pGSCs. Furthermore, its overexpression resulted in reduced expression of translationally controlled tumor protein (TCTP). Bioinformatics analysis and luciferase targeting assay revealed that miR-145-5p exerts its effects by directly targeting TCTP. The expression of TCTP was significantly upregulated in pGSCs, and its silencing suppressed the proliferation and increased the apoptosis of pGSCs. Moreover, upregulation of TCTP attenuated the effect of miR-145-5p overexpression on the viability and apoptosis of pGSCs. The results of

To investigate the efficacy and safety of intravenous thrombolysis combined with mechanical stent interventional thrombectomy in the treatment of acute ischemic stroke.A retrospective analysis was carried out for clinical data of 118 patients with acute ischemic stroke. The patients enrolled were divided into control group (recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis) and thrombectomy group (mechanical stent interventional thrombectomy based on rt-PA intravenous thrombolysis). The vascular recanalization rate and clinical efficacy after treatment were compared between the two groups. National Institutes of Health Stroke Scale (NIHSS) was used to identify the degree of neurological impairment in all patients before and after treatment, and Barthel Index was used to assess their activity of daily living. Moreover, the changes in the levels of T-lymphocyte subpopulation in peripheral blood and immuno-inflammatory factors before and after treatment were compared, and prognosis of patients and incidence of adverse reactions were recorded.The response rate inthrombectomy group (93.2%) was significantly better than that in control group (76.3%). The NIHSS sore and modified Rankin scale (mRS) score after treatment were significantly lower than those before treatment, while the Barthel Index after treatment was distinctly higher than that before treatment. The NIHSS score and mRS score in thrombectomy group obviously declined compared with those in control group at 1 month after treatment. The Barthel Index in thrombectomy group was obviously higher than that in control group at 1 month and 2 months after treatment. Levels of cluster of differentiation 3 (CD3)+, CD3+CD4+, CD4+/CD8+ and natural killer (NK) cells in peripheral blood at 6 months after treatment evidently rose compared with those before treatment, while level of CD3+CD8+ evidently declined compared with that before treatment. In thrombectomy group, levels of CD3+, CD3+CD4+, CD4+/CD8+ and NK cells were markedly higher than those in control group, while the level of CD3+CD8+ was markedly lower than that in control group. Besides, in thrombectomy group, levels of serum osteopontin (OPN), malondialdehyde (MDA) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were evidently lower than those in control group at 1 month after treatment, while the level of serum superoxide dismutase (SOD) was evidently higher than that in control group. Compared with that in control group, the acute vascular reocclusion rate in thrombectomy group was significantly decreased at 3 months after treatment (10.2% vs. 22.0%).Intravenous thrombolysis combined with mechanical stent interventional thrombectomy can effectively promote the vascular recanalization, improve the neurological function and activity of daily living of patients, reinforce the immunological function, inhibit the oxidative stress response and improve the prognosis of patients.Cilj je bio da se istrži efikasnost i bezbednost intravenske trombolize u kombinaciji sa mehanikom intervencijskom trombektomijom stentom u lečenju akutnog ishemijskog moždanog udara.Urađena je retrospektivna analiza kliničkih podataka 118 pacijenata sa akutnim ishemijskim moždanim udarom. Uključeni pacijenti su podeljeni u kontrolnu grupu (rekombinantni tkivni aktivator plazminogena (rt-PA) intravenska tromboliza) i grupu za trombektomiju (interventna trombektomija mehaničkim stentom na bazi rt-PA intravenske trombolize). Stopa vaskularne rekanalizacije i klinika efikasnost nakon tretmana upoređivani su između dve grupe. Skala Nacionalnog instituta za zdravlje moždanog udara (NIHSS) je korišćena za identifikaciju stepena neurološkog oštećenja kod svih pacijenata pre i posle lečenja, a Bartel indeks je korišćen za procenu njihove aktivnosti u svakodnevnom životu. Pored toga, upoređene su promene nivoa subpopulacije T-limfocita u perifernoj krvi i imunoinflamatornih faktora pre i posle tretmana i zabeležena je prognoza pacijenata i incidencija neželjenih reakcija.Stopa odgovora grupe intrombektomije (93,2%) bila je značajno bolja od one u kontrolnoj grupi (76,3%). Rezultati NIHSS bolova i modifikovane Rankinove skale (mRS) nakon tretmana bili su značajno niži od onih pre tretmana, dok je Barthelov indeks nakon tretmana bio znatno viši od onog pre tretmana. NIHSS skor i mRS skor u grupi sa trombektomijom očigledno su opali u poređenju sa onima u kontrolnoj grupi 1 mesec nakon tretmana. Barthelov indeks u grupi sa trombektomijom bio je očigledno viši od onog u kontrolnoj grupi 1 mesec i 2 meseca nakon tretmana. Nivoi klastera diferencijacije 3 (CD3)+, CD3+CD4+, CD4+/CD8+ ćelija prirodnog ubice (NK) u perifernoj krvi 6 meseci nakon tretmana su očigledno porasli u poređenju sa onima pre tretmana, dok je nivo CD3+CD8+ očigledno opao u poređenju sa tim pre lečenja. U grupi sa trombektomijom, nivoi CD3+, CD3+CD4+, CD4+/CD8+ i NK ćelija su bili značajno viši od onih u kontrolnoj grupi, dok je nivo CD3+CD8+ bio značajno niži nego u kontrolnoj grupi. Osim toga, u grupi sa trombektomijom, nivoi serumskog osteopontina (OPN), malondialdehida (MDA) i N-terminalnog pro-B-tipa natriuretičkog peptida (NT-proBNP) bili su evidentno niži od onih u kontrolnoj grupi 1 mesec nakon tretmana, dok je nivo serumske superoksid dismutaze (SOD) bio je evidentno viši nego u kontrolnoj grupi. U poređenju sa onim u kontrolnoj grupi, stopa akutne vaskularne reokluzije u grupi sa trombektomijom je značajno smanjena 3 meseca nakon tretmana (10,2% naspram 22,0%).Intravenska tromboliza u kombinaciji sa mehaničkom intervencijskom trombektomijom stentom mže efikasno promovisati vaskularnu rekanalizaciju, poboljšati neurološku funkciju i aktivnost svakodnevnog života pacijenata, ojačati imunološku funkciju, inhibirati odgovor na oksidativni stres i poboljšati prognozu pacijenata.

Atrial fibrillation is an "invisible killer" of human health. It often induces high-risk diseases, such as myocardial infarction, stroke, and heart failure. Fortunately, atrial fibrillation can be diagnosed and treated early. Low-level vagus nerve stimulation (LL-VNS) is a promising therapeutic method for atrial fibrillation. However, some fundamental challenges still need to be overcome in terms of flexibility, miniaturization, and long-term service of bioelectric stimulation devices. Here, we designed a closed-loop self-powered LL-VNS system that can monitor the patient's pulse wave status in real time and conduct stimulation impulses automatically during the development of atrial fibrillation. The implant is a hybrid nanogenerator (H-NG), which is flexible, light weight, and simple, even without electronic circuits, components, and batteries. The maximum output of the H-NG was 14.8 V and 17.8 μA (peak to peak). In the in vivo effect verification study, the atrial fibrillation duration significantly decreased by 90% after LL-VNS therapy, and myocardial fibrosis and atrial connexin levels were effectively improved. Notably, the anti-inflammatory effect triggered by mediating the NF-κB and AP-1 pathways in our therapeutic system is observed. Overall, this implantable bioelectronic device is expected to be used for self-powerability, intelligentization, portability for management, and therapy of chronic diseases.

Retinoblastoma is a common intraocular malignant tumor in children. However, the molecular and genetic mechanisms of retinoblastoma remain unclear. The gene expression dataset GSE110811 was retrieved from Gene Expression Omnibus. After preprocessing, coexpression modules were constructed by weighted gene coexpression network analysis (WGCNA), and modules associated with clinical traits were identified. In addition, functional enrichment analysis was performed for genes in the indicated modules, and protein‑protein interaction (PPI) networks and subnetworks were constructed based on these genes. Eight coexpression modules were constructed through WGCNA. Of these, the yellow module had the highest association with severity and age (r=0.82 and P=3e‑07; r=0.72 and P=3e‑05). The turquoise module had the highest association with months (r=‑0.63 and P=5e‑04). The genes in the two modules participate in multiple pathways of retinoblastoma, and by combining the PPI network and subnetworks; 10 hub genes were identified in the two modules. The present study identified coexpression modules and hub genes associated with clinical traits of retinoblastoma, providing novel insight into retinoblastoma progression.

The vascular interventional surgery (VIS) is the most popular treatment for the cardiovascular and cerebrovascular diseases. Master-slave VIS robot is a promising technology to further improve the operation accuracy and surgical safety of both the patient and surgeon. The surgical outcome of robot assisted VIS highly depends on surgeon’s operating skills. However, current VIS robot systems affect the exerting of surgeon’s operating skills with different degrees due to the master manipulators with rigid-link structure or low detecting accuracy. To address this issue, a novel vascular interventional surgery robot based on surgeon’s operating skills is developed in this paper. A master manipulator is developed to contactlessly measure the surgeon’s operating motion. The surgeon operates the catheter with no limit, just as the operating manner in conventional VIS. It is enabled by measuring the catheter’s axial motion through tracking the edge of a series of markers with a macro camera, and by measuring the catheter’s rotational motion via a high-precise MEMS (Micro-Electro-Mechanic-System) gyroscope. Then, the developed master manipulator is integrated with a slave robot to construct the master-slave VIS robot system. Experimental results show that the detecting accuracy of the developed master manipulator are 0.71° and 0.104mm. Experimental results of surgical tasks implemented in EVE (endovascular evaluator) indicate that the developed robot system is superior to the system using a phantom as the master manipulator according to the metrics including operating time, path length, maximum speed and maximum accelerate.

Clinical neurorestorative cell therapies for stroke have been explored for over 20 years. Majority cell therapies have shown neurorestorative effects for stroke on non-double-blind studies. In this review, we summarize types of cell transplantation, transplanted routes, therapeutic time windows, dosage, results of exploring trials or clinical studies, results of multicenter, double-blind or observing-blind, randomized, placebo-controlled clinical trials. The clinical application prospects of majority cell therapies for stroke need to prove their neurorestorative effects through trials with higher-level evidence-based medical evidence. Currently olfactory ensheathing cell is only one kind of cell to show neurorestorative effects through multicenter, double-blind, randomized, placebo-controlled clinical trials, which should be explored to optimize themselves effects and combination with others.

The purpose of this study was to elucidate the role of Baicalein in accelerating invasiveness and inducing apoptosis of glioma cells through the phosphatidilinositol 3-kinase/protein kinase B (PI3K/Akt) pathway.U251 glioma cells were treated with different doses of Baicalein (10, 20 or 40 μM) for different time periods (12, 24, 36 or 48 h). Changes in viability, clonality, cell cycle distribution and apoptosis in Baicalein-treated U251 cells were assessed. Meanwhile, relative levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 in U251 cells were detected. Western blot was conducted to examine protein levels of p-Akt and Akt in Baicalein-treated U251 cells.Baicalein treatment attenuated dose-dependently and time-dependently the viability and clonality in U251 cells. It induced cell cycle arrest in G0/G1 phase and cell apoptosis of U251 cells. After Baicalein treatment, the relative levels of MMP-2 and MMP-9 were dose-dependently downregulated. Baicalein treatment activated the PI3K/Akt pathway. Notably, inhibitory effects of Baicalein treatment on MMP levels and invasiveness in glioma were blocked by the application of LY294002 (PI3K/Akt inhibitor), and stimulated by the application of IGF-1 (PI3K/Akt activator).Baicalein treatment is able to suppress invasiveness and induce apoptosis of glioma cells through inactivating the PI3K/Akt pathway.

The Neurorestoratology discipline is getting worldwide attention from the clinicians, basic scientists, students and policy makers alike. Accordingly, this year too, the discipline has made profoun ...

Shiqing Feng,1,* Juan Xiao,2,3,* Fabin Han,4 Lin Chen,5 Wenyong Gao,2,3 Gengsheng Mao,2 Hongyun Huang2,3 On behalf of Neurorestoratology Professional Committee of Chinese Medical Doctors Association (Chinese Association of Neurorestoratology) 1International Science and Technology Cooperation Base of Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of China; 2Institute of Neurorestoratology, The General Hospital of Chinese People’s Armed Police Forces, Beijing 100039, People’s Republic of China; 3Cell Therapy Center, Beijing Hongtianji Neuroscience Academy, Beijing 100043, People’s Republic of China; 4The Institute for Tissue Engineering and Regenerative Medicine, Liaocheng University/Liaocheng People’s Hospital, Liaocheng 252000, People’s Republic of China; 5Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing 100040, People’s Republic of China *These authors contributed equally to this work Abstract: In order to promote the clinical use of neural progenitor or precursor cells for treating neurological diseases and damage, we need to standardize culture procedures for these cells. The Chinese Association of Neurorestoratology put forward these standards for training operators, standardized use and management of materials and equipment, standardized isolation and culture for neural progenitor/precursor cells, and the standardized management in preservation, transport, and related safe operation procedures of the neural progenitors. These cultures and quality control standards also include the Good Manufacturing Practice environment, routine maintenance as well as the monitoring and reporting of the clinical-grade neural progenitor cells. The aim of these standards is to improve the therapeutic efficacy and minimize the possible side effects from lake of quality control. Keywords: standardization, cell culture, quality control, neural progenitor cells, neural precursor cells, neurorestoratology

To observe the effect of early goal directed sedation (EGDS) on cerebral oxygen metabolism in patients with acute brain injury.A prospective cohort study was conducted. A total of 108 patients with acute brain injury admitted to the intensive care unit (ICU) of the Third Medical Center of the PLA General Hospital from January 2015 to December 2019 were enrolled. According to the patient's condition, dexmedetomidine contraindication and tolerance, and combined with the wishes of patients' families, they were divided into EGDS group and on-demand sedation group. Routine treatments such as surgery, mechanical ventilation, dehydration and reduction of intracranial pressure with mannitol, hemostasis or antiplatelets therapy were given according to the patient's condition. All patients were continuously given sufentanil by intravenous infusion for analgesia. Patients in the EGDS group were sedated by continuously intravenous infusion of dexmedetomidine (0.2-0.7 μg×kg(1) Among the 108 patients, 3 patients with cerebral hemorrhage received secondary surgery or had worsening of cerebral hernia were excluded. 105 patients were enrolled in the study, including 54 patients in the EGDS group and 51 patients in the on-demand sedation group. There were no statistically significant differences in gender, age, type of craniocerebral injury, GCS score, proportion of mechanical ventilation and operation ratio between the two groups. (2) Compared with before sedation, Lac, CEROCompared with the on-demand sedation, EGDS could reduce cerebral oxygen metabolism, improve the coma degree, and reduce the severity of the disease in patients with acute brain injury.

Clinical neurorestorative cell therapies for stroke have been explored for over 20 years. Majority cell therapies have shown neurorestorative effects for stroke on non-double-blind studies. In this review, we summarize types of cell transplantation, transplanted routes, therapeutic time windows, dosage, results of exploring trials or clinical studies, results of multicenter, double-blind or observing-blind, randomized, placebo-controlled clinical trials. The clinical application prospects of majority cell therapies for stroke need to prove their neurorestorative effects through trials with higher-level evidence-based medical evidence. Currently olfactory ensheathing cell is only one kind of cell to show neurorestorative effects through multicenter, double-blind, randomized, placebo-controlled clinical trials, which should be explored to optimize themselves effects and combination with others.

To investigate the value and feasibility of early goal directed sedation (EGDS) in patients with acute brain injury.A total of 110 patients with acute brain injury who were admitted to intensive care unit (ICU) of the Third Medical Center of the Chinese People's Liberation Army General Hospital from January 2015 to March 2019 were included and randomly divided into EGDS group and standard sedation group (STD) using the random number table. Patients in the EGDS group were sedated by continuous intravenous infusion of dexmedetomidine (initial dose of 0.2 μg×kg(1) Among the 110 patients, patients who received the second surgery due to cerebral hemorrhage, had worsening of cerebral hernia, withdrew during the course of the study, or whose family members abandoned treatment were excluded from the study. Finally, 105 patients were enrolled in the study, including 56 patients in the EGDS group and 49 in the STD group. There was no significant difference in gender, age, types of brain injury, baseline APACHE II or GCS score or rate of mechanical ventilation between the two groups. (2) Compared with before sedation, heart rate (HR) significantly decreased till 72 hours after sedation in both groups, and the decrease in the EGDS groups was more obvious as compared with the STD group (bpm: 70.49±7.53 vs. 79.83±9.48, P0.05). Besides HR, significant improvement was found in the APACHE II and GCS scores in the STD group at 72 hours of sedation as compared with before sedation, and no significant difference was found in other indicators. Compared with before sedation, arterial partial pressure of carbon dioxide (PaCOEGDS can improve the GCS score and BIS value of patients with acute brain injury, suggesting that the EGDS is safe and feasible, which can help improve neurological function in patients with acute brain injury.

Hongyun Huang,1 Lin Chen,2 Qingyan Zou,3 Fabin Han,4 Tiansheng Sun,5 Gengsheng Mao,1 Xijing He6 1Institute of Neurorestoratology, General Hospital of Armed Police Forces, 2Department of Neurosurgery, Yuquan Hospital, Tsinghua University, Beijing, 3Guangdong 999 Brain Hospital, Guangzhou, 4Centre for Stem Cells and Regenerative Medicine, Affiliated Hospital of Taishan Medical University, Liaocheng, Shandong, 5Department of Orthopedics, Beijing Army General Hospital, Beijing, 6Second Department of Orthopedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China On behalf of the Chinese Association of Neurorestoratology and Chinese Branch of the International Association of Neurorestoratology Abstract: Cell therapy has been shown to be a key clinical therapeutic option for central ­nervous system disease or damage, and >30 types of cells have been identified through preclinical studies as having the capacity for neurorestoration. To standardize the clinical procedures of cell therapy as one of the strategies for treating neurological disorders, the first set of guidelines governing the clinical application of neurorestoration was completed in 2011 by the Chinese Branch of the International Association of Neurorestoratology. Given the rapidly advancing state of the field, the Neurorestoratology Professional Committee of Chinese Medical Doctor Association (Chinese Association of Neurorestoratology) and the Chinese Branch of the International Association of Neurorestoratology have approved the current version known as the “Clinical Cell Therapy Guidelines for Neurorestoration (China Version 2016)”. We hope this guideline will reflect the most recent results demonstrated in preclinical research, transnational studies, and evidence-based clinical studies, as well as guide clinical practice in applying cell therapy for neurorestoration. Keywords: cell therapy, neurorestoration, China, clinical application

Basilar artery occlusion (BAO) remains one of the most devastating subtypes of ischemic stroke, and prognosis is poor if early recanalization is not achieved. The purpose of this study was to evaluate the safety and technical feasibility of mechanical thrombectomy with the Solitaire AB stent (Covidien, Irvine, CA, USA) for the treatment of acute BAO through a single-center experience. Twenty-one patients with acute BAO were treated with mechanical thrombectomy with the Solitaire AB stent device between 1st September 2011 and 1st December 2014. Recanalization was assessed using the Thrombolysis in Cerebral Infarction (TICI) scale system. Clinical outcome was established at discharge by The National Institute of Health Stroke Scale (NIHSS), and the mean time from symptom onset to recanalization determined. Authors had access to identifying information during or after data collection. The clinical status of patients on admission was severe, with a mean NIHSS score of 25.57±5.20 (range: 16-38), and the number of patients with TICI 2b or 3 was 0. The mean time from symptom onset to recanalization was 579.00±188.78min (range: 360-960min). At 3-month follow-up, eight (38.1%) patients had a good clinical outcome. At follow-up, the trial of ORG 10172 in acute stroke treatment (TOAST) classification was large-vessel atherosclerosis in 13 patients (61.9%), cardioembolic in seven patients (33.3%), and undetermined in one patient (4.8%). In our series, application of the Solitaire AB stent retriever in acute BAO resulted in a high recanalization rate without procedural complications, and with good clinical outcome. Further prospective trials are needed to confirm the potential clinical benefit of this treatment approach.

An accurate assessment of surgical operation skills is essential for improving the vascular intervention surgical outcome and the performance of endovascular surgery robots. In existing studies, subjective and objective assessments of surgical operation skills use a variety of indicators, such as the operation speed and operation smoothness. However, the vascular conditions of particular patients have not been considered in the assessment, leading to deviations in the evaluation. Therefore, in this paper, an operation skills assessment method including the vascular difficulty level index for catheter insertion at the aortic arch in endovascular surgery is proposed. First, the model describing the difficulty of the vascular anatomical structure is established with characteristics of different aortic arch branches based on machine learning. Afterwards, the vascular difficulty level is set as an objective index combined with operating characteristics extracted from the operations performed by surgeons to evaluate the surgical operation skills at the aortic arch using machine learning. The accuracy of the assessment improves from 86.67 to 96.67% after inclusion of the vascular difficulty as an evaluation indicator to more objectively and accurately evaluate skills. The method described in this paper can be adopted to train novice surgeons in endovascular surgery, and for studies of vascular interventional surgery robots. Graphical abstract Operation skill assessment with vascular difficulty for vascular interventional surgery.

PurposeThree-dimensional (3D) scans with flat detector angiographic systems are widely used for neurointerventions by providing detailed vascular information. However, its associated radiation dose and streak metal artifact generated by implanted treatment devices remain issues. This work evaluates the feasibility and clinical value of volume of interest imaging combined with metal artifact reduction (VOI+MAR) to generate high quality 3D images with reduced radiation dose and metal artifacts.Material and methodsFull volume (FV) and VOI scans were acquired in 25 patients with intracranial aneurysms and treated with either endovascular coiling (n=9) or stent assisted coiling (n=16) procedures. FV and VOI scans were reconstructed with conventional syngo DynaCT and VOI +MAR prototype software, respectively.ResultsQuantitative evaluation results demonstrated that compared with standard FV syngo DynaCT images, overall image quality was improved in the VOI+MAR reconstructed images, with streak metal artifacts considerably reduced or even removed; details of soft tissue in the vicinity of the metal devices was well preserved or recovered in the majority of cases. Radiation dose to patients calculated by dose area product was found to be significantly reduced using VOI scans.ConclusionThis study confirmed the feasibility of using VOI+MAR prototype software to achieve high image quality of a small volume of clinical interest and to reduce radiation dose. This technique has potential to improve patient safety and treatment outcomes.

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version “Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)”. The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility. Refereed/Peer-reviewed

Qiang Ao,1,* Juan Xiao,2,3,* Yanqiu Yu,4 Gengsheng Mao,2 Qingyan Zou,5 Wenyong Gao,2,3 Hongyun Huang2,3 On behalf of Neurorestoratology Professional Committee of Chinese Medical Doctor Association (Chinese Association of Neurorestoratology) 1Department of Tissue Engineering, China Medical University, Shen Yang, 2Institute of Neurorestoratology, General Hospital of Armed Police Forces, Beijing, 3Cell Therapy Center, Beijing Hongtianji Neuroscience Academy, Beijing, 4Department of Pathophysiology, China Medical University, Shen Yang, 5Guangdong 999 Brain Hospital, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Formulating common standards for the culture and quality control of umbilical cord mesenchymal stromal cells (MSCs) is crucial for the standardization of clinical neurorestorative therapy. But to date, there have been no standardized guidelines for the culture and quality control of MSCs in neurorestorative clinical application. Based on a relatively comprehensive review of published clinical studies as well as the existing methods of MSC culture and quality control, the Chinese Association of Neurorestoratology has developed standards for the culture and quality control of umbilical cord MSCs which possess the potential in neurorestorative clinical application. These guidelines include standardized training and management procedures for laboratory operators; standardized use and management of materials and equipment; standardized collection, culture and proliferation of umbilical cord MSCs; standardized management for cell preservation, transport and related safeguard measures; as well as standardization of a clean environment, routine maintenance and related tests and examinations and so on. These guidelines represent the minimum required standards for the culture and quality control of umbilical cord MSCs for potential use in current neurorestorative clinical therapy, and will be further optimized according to the progress of preclinical and clinical studies. Keywords: standardization, cell culture, quality control, mesenchymal stromal cells, clinical treatment, neurorestoratology, translational medicine

Adipose stromal cells (ASC) can protect neurons when administered to brains due to secreted trophic factors. Our previous studies demonstrated that several neurotrophic factors such as brain-derived neurotropic factor (BDNF) and insulin like growth factor-1 (IGF-1) in ASC conditioned media (ASC-CM) can protect brains against hypoxic-ischemic (HI) injury in neonatal rats. In this study, we demonstrated that human ASC-CM potently blockeds caspase-3 mediated cortical neuronal apoptosis under in vitro oxygen-glucose deprivation (OGD). Interestingly, tissue inhibitor of metalloproteinase 1 (TIMP1), a non neurotrophic factor, played a significant role in the ASC-CM-induced neural protection against OGD. Thus, this study establishes the therapeutic potential of TIMP1 together with other neurotrophic factors in ASC-CM for treating cerebral HI disorders.

Juan Xiao,1,2 Lin Chen,3 Gengsheng Mao,1 Wenyong Gao,1,2 Ming Lu,4 Xijing He,5 Hongyun Huang1,2 On behalf of the Neurorestoratology Professional Committee of Chinese Medical Doctors Association (Chinese Association of Neurorestoratology) 1Institute of Neurorestoratology, The General Hospital of Chinese People’s Armed Police Forces, Beijing, People’s Republic of China; 2Cell Therapy Center, Beijing Hongtianji Neuroscience Academy, Beijing, People’s Republic of China; 3Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing, People’s Republic of China; 4Department of Neurosurgery, 163 Hospital of PLA (Second Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, People’s Republic of China; 5Department of Orthopedics, Second Affiliated Hospital of Xi’an Jiaotong University, Xian, Shanxi Provine, People’s Republic of China Abstract: Olfactory ensheathing cells (OECs) are a novel type of glial cell that can perform and promote many neurorestorative processes in vivo after transplant. To date, dozens of preclinical and clinical studies have confirmed that OECs have unique restoring effects in animal models and human subjects with neurological degeneration or damage, such as spinal cord injury, stroke, cerebral palsy, traumatic brain injury, and motor neuron disease (amyotrophic lateral sclerosis). To ensure the safety and effectiveness of clinical applications utilizing this type of cell, it is important to standardize cell-culture and quality-control processes. Based on a comprehensive review of published clinical studies, as well as existing methods of OEC culture and quality control currently utilized by hospitals and biomedical enterprises, the Chinese Association of Neurorestoratology has developed a set of standards for the culture and quality control of olfactory ensheathing cells for use in clinical applications. These guidelines include standardized training and management procedures for laboratory operators; standardized use and management of materials and equipment; standardized collection, culture, and proliferation of OECs obtained from fetal olfactory bulbs; standardized management for cell preservation, transport, and related safeguard measures; and the standardization of a clean environment, routine maintenance, and related tests and examinations. Our goal in publishing this set of standards is to promote the worldwide safety, effectiveness, and replicability of utilizing OECs obtained from fetal olfactory bulbs for neurorestorative clinical application. Keywords: standardization, cell culture, quality control, olfactory ensheathing glial cells, neurorestorative clinical application, neurorestoratology, translational medicine

To investigate factors that may be associated with urinary incontinence (UI) in abdominal obese and non-obese adult males.Data were analyzed for 2671 men (≥40 years of age) who participated in the National Health and Nutrition Examination Survey (2005-2008). We define abdominal obesity as a waist circumference102 cm. Men with Incontinence Severity Index ≥3 were defined as having UI. Logistic regression analyses were used to identify factors associated with stress and urge UI.Multivariate analysis found that in abdominal obese men, stress UI was associated with enlarged prostate (odds ratio [OR] = 2.20, 95% confidence interval [CI]: 1.16-4.16), chronic respiratory tract disease (OR = 2.78, 95% CI: 1.55-4.97), and major depression (OR = 4.79, 95% CI: 1.79-12.84). In non-obese men, arthritis was associated with stress UI (odds ratio = 3.37, 95% CI: 1.06-10.73). Urge UI in abdominally obese men was associated with age ≥65 years (OR = 1.67, 95% CI: 1.05-2.67), being non-Hispanic black (OR = 1.63, 95% CI: 1.06-2.52), and with enlarged prostate (OR = 2.30, 95% CI: 1.54-3.40), arthritis (OR = 1.39, 95% CI: 1.03-1.88), and major depression (OR = 2.96, 95% CI: 1.89-4.64). Urge UI in non-obese men was associated with current smoking (OR = 1.79, 95% CI: 1.01-3.17), major depression (OR = 2.60, 95% CI: 1.33-5.09) and vitamin D deficiency (OR = 1.61, 95% CI: 1.01-2.59).Factors associated with urinary incontinence varied with abdominal obesity status and type of UI. The findings identify important contributors to urinary incontinence that clinicians should consider to help manage and effectively treat the condition.

Cerebral ischemic stroke is a very common condition that can cause death and disability. Studies have confirmed that stem cells have therapeutic effects if administered after a stroke. There is still a great deal of debate regarding the best route for cell transplantation. Intravascular delivery is the most commonly used one. In this study, the therapeutic effects of bone marrow stem cells (BMSCs) delivered by intra-arterial (IA) and intravenous (IV) injection in a rat transient middle cerebral artery occlusion model (MCAO) are compared. Histological analysis demonstrated that the IA route bypasses the pulmonary system and directs the cells to the ischemic parts of the brain more efficiently. The BMSCs delivered via the IA route promoted angiogenesis and improved functional recovery. The cerebral blood flow (CBF) of the rats was monitored during the IA injection process. No reduction in CBF or microstrokes was detected. Brain perfusion and metabolism, as evaluated by SPECT and PET, were better in rats treated with cells delivered via IA. Results showed that the IA route is a safe and effective way to transplant hBMSCs. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

The aim of the study was to examine treatment of cerebral hemorrhages with bone-marrow or human umbilical cord-derived mesenchymal stem cells (BMSCs or Hu-MSCs) and conventional surgical approaches, and determine and compare the effectiveness, feasibility, safety and reproducibility of each method. A retrospective analysis was performed on a cohort of cell-treated cerebral hemorrhage patients from October 1, 2007 to October 1, 2009. A total of 24 patients, all of whom received conventional surgical treatment, were classified as follows: i) The control group consisted of 8 patients who received only hematoma removal surgery, ii) the autologous group consisted of 7 patients who received additional autologous bone marrow mononuclear cell transplantation, and iii) the allograft group consisted of 9 patients who received additional umbilical cord mononuclear cell transplantation. After conventional hematoma removal surgery and X-ray supervision within 24 h and at 7 days, neurological disability and function tests were completed 3, 6, 12, 36 and 60 months later. The T-cell marker plasma levels were analyzed after 60 months. The results showed that, at approximately 3.5 months after graft the hematomas in all the groups were completely reabsorbed as observed on computed tomography scans. However, the functional outcomes in the cell-transplanted groups were better than in the control group after 5 years. While the National Institutes of Health Stroke Scale, modified Rankin score and modified Barthel index scores were simliar in the cell-transplanted groups, patients in the allograft group had better outcomes than those in the autologous graft group starting at 3 months and until the end of the follow-up period. The serum levels of T-cell markers CD4, CD56 and human leukocyte antigen-DR in the allograft group showed no signs of immunogenic graft complications and there were no significant differences in T-cell subtypes among the patient groups. The results of the present study suggest that, treatment of cerebral hemorrhage patients can be safely and effectively accomplished using Hu-MSC grafting and larger clinical trials should be considered in the future.

Meningeal melanocytoma is a kind of extremely rare pigmented tumor of the central nervous system, which often occurs in the groove around the base of the brain and spinal pia mater. Age of onset is 40 to 50 years old, mostly presenting a benign course of disease and the prognosis is good. Case reports of partial invasion or metastasis from lesions are even rarer. This report described a case of 56-year-old meningeal melanoma patient with partial skull and muscle invasion at the lantooccipital transition zone. Intraoperative histological examination showed moderate malignancy and Ki-67 index was 10%.

Cell therapies in the treatment of central nervous system disease and injury, such as spinal cord injury, multiple sclerosis, sequelae of stroke, amyotrophic lateral sclerosis, and cerebral palsy, have been studied in the clinic for the last 10-20 years. Excitingly, many studies have demonstrated that most patients appear to have some functional improvement following administration of different types of cells by different routes with relatively low risk and good tolerability. However, there are some misconceptions that hinder the development of cell-based neurorestorative strategies. It is a considerable challenge but also an opportunity for physicians in neurorestoratology to face these issues. This review briefly outlines the progress made in neurorestoratology, discusses the relevant issues, and attempts to correct the misconceptions.