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lateral lymph node dissection for low rectal cancer: Is it necessary?

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World Journal of Gastroenterology 2019年第31期25卷 4294-4299页

作者： Niki Christou Jeremy Meyer Christian Toso Frédéric Ris Nicolas Christian Buchs Service de Chirurgie Digestive Endocrinienne et GénéraleCHU de LimogesLimoges Cedex 87042France Division of Digestive Surgery University Hospitals of GenevaGenève 1211Switzerland Unit of Surgical Research University of GenevaGenève 1206Switzerland

Rectal cancer constitutes a major public health issue.Total mesorectal excision has remained the gold standard treatment for mid and low rectal tumors since its introduction in the late 1980s.Removal of all lymph nodes located in the mesorectum has indeed improved pathological and oncological outcomes.However,when cancer spreads to the lateral lymph nodes(located along the iliac and obturator arteries)Western and Japanese practices differ.Where the Western guidelines consider this condition as an advanced form of the disease and use neoadjuvant radiochemotherapy liberally,the Japanese guidelines define it as a local disease and proceed to lateral lymph node dissection with or without neoadjuvant treatment.Herein,we review the current literature regarding both therapeutic strategies,with the aim of contributing to potential improvements in treatment and outcome for patients with low and mid rectal cancer.

关键词： Total mesorectum excision Mesorectal resection lateral node metastasis Extended lymphadenectomy

Safety of intrathecal injection of Wharton's jellyderived mesenchymal stem cells in amyotrophic lateral sclerosis therapy

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Neural Regeneration Research 2019年第2期14卷 313-318页

作者： Monika Barczewska Mariusz Grudniak Stanis?aw Maksymowicz Tomasz Siwek Tomasz O?dak Katarzyna Jezierska-Wo?niak Dominika G?adysz Wojciech Maksymowicz Department of Neurology and Neurosurgery School of Medicine Collegium Medicum-University of Warmia and Mazury in Olsztyn University Clinical Hospital in Olsztyn Instytut Terapii Komórkowych w Olsztynie(Cell Therapies Institute FamiCord Group) Polski Bank Komórek Macierzystych (PBKM FamiCord Group) Department of Psychology Clinical Logopedics and Social Science in Medicine Faculty of Health Sciences Collegium Medicum-University of Warmia and Mazury in Olsztyn Department of Neurology and Neurosurgery Laboratory of Regenerative Medicine School of Medicine Collegium Medicum-University of Warmia and Mazury in Olsztyn

Animal experiments have confirmed that mesenchymal stem cells can inhibit motor neuron apoptosis and inflammatory factor expression and increase neurotrophic factor expression. Therefore, mesenchymal stem cells have been shown to exhibit prospects in the treatment of amyotrophic lateral sclerosis. However, the safety of their clinical application needs to be validated. To investigate the safety of intrathecal injection of Wharton's jelly-derived mesenchymal stem cells in amyotrophic lateral sclerosis therapy, 43 patients(16 females and 27 males, mean age of 57.3 years) received an average dose of 0.42 × 106 cells/kg through intrathecal administration at the cervical, thoracic or lumbar region depending on the clinical symptoms. There was a 2 month interval between two injections. The adverse events occurring during a 6-month treatment period were evaluated. No adverse events occurred. Headache occurred in one case only after first injection of stem cells. This suggests that intrathecal injection of Wharton's Jelly-derived mesenchymal stem cells is well tolerated in patients with amyotrophic lateral sclerosis. This study was approved by the Bioethical Committee of School of Medicine, University of Warmia and Mazury in Olsztyn, Poland(approval No. 36/2014 and approval No. 8/2016). This study was registered with the ClinicalTrials.gov(identifier: NCT02881476)on August 29, 2016.

关键词： amyotrophic lateral sclerosis stem cells therapy intrathecal injections Wharton's jelly-derived mesenchymal stem cells adverse events safety cerebrospinal fluid neural regeneration

Poly-PR in C9ORF72-Related Amyotrophic lateral Sclerosis/Frontotemporal Dementia Causes Neurotoxicity by Clathrin-Dependent Endocytosis

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Neuroscience Bulletin 2019年第5期35卷 889-900页

作者： Rui Wang Xingyun Xu Zongbing Hao Shun Zhang Dan Wu Hongyang Sun Chenchen Mu Haigang Ren Guanghui Wang Laboratory of Molecular Neuropathology Jiangsu Key Laboratory of Neuropsychiatric Diseases and Department of Pharmacology College of Pharmaceutical SciencesSoochow University

GGGGCC repeat expansions in the C9 ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia(c9 ALS/FTD). It has been reported that hexanucleotide repeat expansions in C9 ORF72 produce five dipeptide repeat(DPR) proteins by an unconventional repeat-associated non-ATG(RAN)translation. Within the five DPR proteins, poly-PR and poly-GR that contain arginine are more toxic than the other DPRs(poly-GA, poly-GP, and poly-PA). Here, we demonstrated that poly-PR peptides transferred into cells by endocytosis in a clathrin-dependent manner, leading to endoplasmic reticulum stress and cell death. In SH-SY5 Y cells and primary cortical neurons, poly-PR activated JUN amino-terminal kinase(JNK) and increased the levels of p53 and Bax. The uptake of poly-PR peptides by cells was significantly inhibited by knockdown of clathrin or by chlorpromazine, an inhibitor that blocks clathrin-mediated endocytosis. Inhibition of clathrin-dependent endocytosis by chlorpromazine significantly blocked the transfer of poly-PR peptides into cells, and attenuated poly-PRinduced JNK activation and cell death. Our data revealed that the uptake of poly-PR undergoes clathrin-dependentendocytosis and blockade of this process prevents the toxic effects of synthetic poly-PR peptides.

关键词： Amyotrophic lateral sclerosis C9ORF72 Poly-PR Clathrin ER stress

Prognostic value of time to generalization in 71 Chinese patients with sporadic amyotrophic lateral sclerosis

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Chinese Medical Journal 2019年第9期132卷 1023-1027页

作者： Qiong-Hua Sun Yan-Ran Li Wen-Jie Lan Fei Yang Fang Cui Xu-Sheng Huang Department of Neurology Chinese People's Liberation Army General HospitalBeijing 100853China College of Medicine Nankai UniversityTianjin 300071China

Background:It is important to determine prognostic factors for the outcome of amyotrophic lateral sclerosis (ALS) at an early stage.The time taken for symptoms to spread from spinal or bulbar regions to both (time to generalization;TTG) is considered a strong predictor of survival;however,this has rarely been studied in Asian populations.The aim of this retrospective study was to evaluate potential factors affecting prognosis in Chinese patients with sporadic ALS,with a focus on the association between TTG and overall survival.Methods:Seventy-one patients with sporadic ALS who were hospitalized at Chinese PLA General Hospital from 2009 to 2016 were followed up until December 2017.Survival analysis was performed using univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards models.The clinical data of the patients were recorded and analyzed.Variables studied were age at symptom onset,sex,site of symptom onset,diagnostic latency,TTG,diagnostic category,ALS Functional Rating Scale-revised score,percent predicted forced vital capacity (FVC%),and disease progression rate (DPR) at diagnosis.Results:The mean age at onset was 54 (SD = 10.2) years,and the median survival time from symptom onset was 41 months (95% confidence interval:34–47).By univariate analysis,factors independently affecting survival were age at symptom onset (Log rank = 15.652,P<0.0001),TTG (Log rank = 14.728,P<0.0001),diagnostic latency (Log rank = 11.997,P = 0.001),and DPR (Log rank = 6.50,P = 0.011).In the Cox multivariate model,TTG had the strongest impact on survival time (hazard ratio = 0.926,P = 0.01).Conclusions:TTG can be used as an effective indicator of prognosis in patients with sporadic ALS.

关键词： Amyotrophic lateral sclerosis Time to generalisation (TTG) Prognosis Survival

The Systems Biology of lateral Root Formation: Connecting the Dots

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Molecular Plant 2019年第6期12卷 784-803页

作者： J.A.Santos Teixeira K.H.ten Tusscher Computational Developmental Biology Group Department of Biology Utrecht University Utrecht the Netherlands

The root system is a major determinant of a plant's access to water and nutrients.The architecture of the root system to a large extent depends on the repeated formation of new lateral roots.In this review,we discuss lateral root development from a systems biology perspective.We focus on studies combining experiments with computational modeling that have advanced our understanding of how the auxin-centered regulatory modules involved in different stages of lateral root development exert their specific functions.Moreover,we discuss how these regulatory networks may enable robust transitions from one developmental stage to the next,a subject that thus far has received limited attention.In addition,we analyze how environmental factors impinge on these modules,and the different manners in which these environmental signals are being integrated to enable coordinated developmental decision making.Finally,we provide some suggestions for extending current models of lateral root development to incorporate multiple processes and stages.Only through more comprehensive models we can fully elucidate the cooperative effects of multiple processes on later root formation,and how one stage drives the transition to the next.

关键词： Arabidopsis lateral root developmental stages auxin signaling modules systems biology

Study on variation trend of repetitive nerve stimulation waveform in amyotrophic lateral sclerosis

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Chinese Medical Journal 2019年第5期132卷 542-550页

作者： Li-Lan Fu He-Xiang Yin Ming-Sheng Liu Li-Ying Cui Department of Neurology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing 100730 China Neurosciences Center Chinese Academy of Medical Sciences Beijing 100730China

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower neurons with no effective cure. Electrophysiological studies have found decremental responses during low-frequency repetitive nerve stimulation (RNS) except for diffused neurogenic activities. However, the difference between ALS and generalized myasthenia gravis (GMG) in terms of waveform features is unclear. In the current study, we explored the variation trend of the amplitudes curve between ALS and GMG with low-frequency, positive RNS, and the possible mechanism is discussed preliminarily. Methods: A total of 85 ALS patients and 41 GMG patients were recruited. All patients were from Peking Union Medical College Hospital (PUMCH) between July 1,2012 and February 28,2015. RNS study included ulnar nerve, accessory nerve and facial nerve at 3 Hz and 5 Hz stimulation. The percentage reduction in the amplitude of the fourth or fifth wave from the first wave was calculated and compared with the normal values of our hospital. A 15% decrease in amplitude is defined as a decrease in amplitude. Results: The decremental response at low-frequency RNS showed the abnormal rate of RNS decline was 54.1%(46/85) in the ALS group, and the results of different nerves were 54.1 %(46/85) of the accessory nerve, 8.2%(7/85) of the ulnar nerve and 0%(0/85) of the facial nerve stimulation, respectively. In the GMG group, the abnormal rate of RNS decline was 100%(41/41) at low-frequency RNS of accessory nerves. However, there was a significant difference between the 2 groups in the amplitude after the sixth wave. Conclusions: Both groups of patients are able to show a decreasing amplitude of low-frequency stimulation RNS, but the recovery trend after the sixth wave has significant variation. It implies the different pathogenesis of NMJ dysfunction of these 2 diseases.

关键词： Amyotrophic lateral sclerosis Generalized myasthenia gravis Neuromuscular junction Repetitive nerve stimulation

Influence of Center of Gravity Location on Flight Dynamic Stability in a Hovering Tailless FW-MAV: lateral Motion

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Journal of Bionic Engineering 2020年第1期17卷 148-160页

作者： Loan Thi Kim Au Hoon Cheol Park Department of Smart Vehicle Engineering and Artificial Muscle Research Center Konkuk UniversitySeoul 05029Korea

This paper reports the effect of the Center of Gravity(CG)position on lateral flight dynamic stability of hovering KUBeetle,a tailless FW-MAV,providing further insights on the effects of asymmetries in body mass distribution and wing kinematics.For the current study,the standard linearized equations of motion were applied as in the previous work on longitudinal dynamic stability.The stability derivatives were acquired using the computational fluid dynamic methods via the commercial software of ANSYS Fluent.There exists a stable region for CG between 2.6%and 3.5%of the mean chord below the wing pivot point,in which the lateral motion of hovering KUBeetle is passively stable.For CG below the stable region,because of an unstable oscillatory mode,the lateral motion of the FW-MAV is unstable but can be stabilized using rolling rate feedback.For CG above the stable region,because of a divergence mode,the system remains unstable even with the rolling rate feedback.Comparison with other works on an FW-MAV based on a quasi-steady aerodynamic model and on insect showed similar characteristics for flapping flight.It is also interesting to note that the asymmetries in body mass and wing kinematics can enlarge the stable region of the system by a non-zero Ixz which approaches the root square of√IxIz,a negative LrNp,and a positive Ix2(Ir+Np).Combining the current result with that of the previous work on longitudinal motion,the most beneficial region of the CG for full 6-DOF flight dynamic stability of hovering KUBeetle was suggested.

关键词： FW-MAV center of gravity flight dynamic stability lateral motion asymmetry computational fluid dynamics bioinspired flight

Endogenous Hypoxia in lateral Root Primordia Controls Root Architecture by Antagonizing Auxin Signaling in Arabidopsis

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Molecular Plant 2019年第4期12卷 538-551页

作者： Vinay Shukla Lara Lombardi Sergio lacopino Ales Pencik Ondrej Novak Pierdomenico Perata Beatrice Giuntoli Francesco Licausi Unstitute of Life Sciences Scuola Superiore Sant'Anna Pisa Italy Biology Department University of Pisa Pisa Italy Laboratory of Growth Regulators Centre of the Region Hana for Biotechnological and Agricultural Research Institute of Experimental Botany CAS & Faculty of Science. Palacky University Slechtitelu 27 78371 Olomouc Czech Republic

As non-photosynthesizing organs, roots are dependent on diffusion of oxygen from the external environment and, in some in stances, from the shoot for their aerobic metabolism . Establishment of hypoxic niches in the developing tissues of plants has been postulated as a consequence of insufficient diffusion of oxygen to satisfy the demands throughout development. Here, we report that such niches are established at specific stages of lateral root primordia development in Arabidopsis thaliana grown under aerobic conditions. Using gain- and loss-of-function mutants, we show that ERF-Ⅶ transcription factors, which mediate hypoxic responses, control root architecture by acting in cells with a high level of auxin signaling. ERF-Ⅶs repress the expression of the auxin-induced genes LBD16, LBD18, and PUCHI, which are essential for lateral root development, by binding to their promoters. Our results support a model in which the establishment of hypoxic n iches in the developing lateral root primordia con tributes to the shutting down of key auxin-induced genes and regulates the production of lateral roots.

关键词： Arabidopsis auxin ERF-VII, hypoxia lateral root root development

Adipose-derived stem cell conditioned medium for the treatment of amyotrophic lateral sclerosis: pre-clinical evidence and potential for clinical application

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Neural Regeneration Research 2019年第9期14卷 1522-1524页

作者： Chandler L.Walker Department of Biomedical and Applied Sciences Indiana University School of Dentistry

Amyotrophic lateral sclerosis(ALS)is a devastating progressive neurodegenerative disease that causes death of upper and lower motor neurons(MNs)in the central nervous system(CNS).The disease afflicts most people in prime periods of productivity in life,and it is estimated approximately 200,000 individuals in the United States live with ALS and any given time.Though a significant percentage of individuals with ALS have a genetic or hereditary form of the disease,the majority are sporadic cases with unknown etiologies.Regardless of cause,onset and progression of the disease is similar in all ALS patients,with minor initial outward symptoms followed by rapid deterioration of motor function leading to widespread paralysis,respiratory dysfunction and death.Despite the distressing and debilitating nature of ALS,no cures and limited potential treatment options exist.Therefore,identifying targets for effective therapy leading to delayed disease progression,increased quality of life,and extended lifespan are critical areas of investigation.In addition,identifying biomarkers of disease progression is incredibly important as diagnosis often occurs once the disease is in late stages and lifespan is only an average of 3–5 years after diagnosis.As the cellular and physiological processes known to influence or be involved in ALS are numerous,the complexity of the disease is a major detriment in developing effective therapies.Aside from the ubiquitous death of MNs,inflammatory and immunologic response in the spinal cord,brain and target muscles,and signal pathway changes that precede or are induced by MN death have been identified at multiple stages of disease progression.

关键词： Amyotrophic lateral devastating progressive neurodegenerative disease progression