血清免疫球蛋白GN-糖基的高通量分析——一种消化道癌症的非侵入性生物标志物

免疫球蛋白G(Immunoglobulin G,IgG)的N-糖基化在炎症性疾病的发展中起着重要作用。本研究旨在评价IgG N-糖基在消化道癌症亚型中的诊断效能。从中国医学科学院肿瘤医院招募749名消化道癌症患者,包括食管癌(esophageal cancer,EC)、胃癌(gastric cancer,GC)、结直肠癌(colorectal cancer,CRC)和胰腺癌(pancreatic cancer,PC)患者。采用亲水交互高效液相色谱-超高效液相色谱(hydrophilic interaction liquid chromatography using ultra-performance liquid chromatography,HILIC-UPLC)分析血浆中IgG的N-糖基构成。采用Bio-Plex悬液芯片系统检测方法(Bio-Rad)进行炎症因子检测。采用典型相关分析(canonical correlation analysis,CCA)探索糖基和炎症因子之间的相关性。采用LASSO回归和logistic回归模型,基于检测到的糖基谱建立可用于区分胃肠癌症患者和健康人群诊断模型。与健康对照组相比,EC、GC、CRC和PC患者的唾液酸化和半乳糖基化水平降低,而二等分乙酰葡萄糖胺基化水平在消化道癌症患者中升高。此外,只有胰腺癌患者具有低水平的岩藻糖基化。消化道癌症组的IL-1β、IL-31和sCD40L水平均高于对照组。IgG N-糖基的组成与炎症因子相关(r=0.556)。基于糖基的模型表现出良好的诊断效能,EC、GC、CRC和PC的受试者工作特征曲线下面积(AUC)分别为0.972、0.871、0.867和0.907。这些研究结果表明,IgG N-糖基在调节消化道肿瘤的发病机制中发挥了重要作用。血清IgG N-糖基可以作为潜在的非侵入性辅助消化道癌症临床诊断的方法。

Erratum to Clinical management and survival outcomes of patients with different molecular subtypes of diffuse gliomas in China(2011-2017):a multicenter retrospective study from CGGA

In the published version of Figure 21,an error appeared in Figure 2C on page 1468.In Figure 2C,the Kaplan-Meier estimation of the overall survival of patients with recurrent DG classified according to molecular subtypes was mistakenly covered by the curves of patients with primary DGs during the figure layout process,while the number statistic under the figure is correct.Figure 2C has been updated to correct this mistake.The error does not affect the conclusions of this article.We apologize for the error and for any confusion that it might have caused.

Clinical management and survival outcomes of patients withdifferent molecular subtypes of diffuse gliomas in China(2011–2017):a multicenter retrospective study from CGGA

Objective:We aimed to summarize the clinicopathological characteristics and prognostic features of various molecular subtypes of diffuse gliomas(DGs)in the Chinese population.Methods:In total,1,418 patients diagnosed with DG between 2011 and 2017 were classified into 5 molecular subtypes according to the 2016 WHO classification of central nervous system tumors.The IDH mutation status was determined by immunohistochemistry and/or DNA sequencing,and 1p/19q codeletion was detected with fluorescence in situ hybridization.The median clinical follow-up time was 1,076 days.T-tests and chi-square tests were used to compare clinicopathological characteristics.Kaplan‒Meier and Cox regression methods were used to evaluate prognostic factors.Results:Our cohort included 15.5%lower-grade gliomas,IDH-mutant and 1p/19q-codeleted(LGG-IDHm-1p/19q);18.1%lowergrade gliomas,IDH-mutant(LGG-IDHm);13.1%lower-grade gliomas,IDH-wildtype(LGG-IDHwt);36.1%glioblastoma,IDHwildtype(GBM-IDHwt);and 17.2%glioblastoma,IDH-mutant(GBM-IDHm).Approximately 63.3%of the enrolled primary gliomas,and the median overall survival times for LGG-IDHm,LGG-IDHwt,GBM-IDHwt,and GBM-IDHm subtypes were 75.97,34.47,11.57,and 15.17 months,respectively.The 5-year survival rate of LGG-IDHm-1p/19q was 76.54%.We observed a significant association between high resection rate and favorable survival outcomes across all subtypes of primary tumors.We also observed a significant role of chemotherapy in prolonging overall survival for GBM-IDHwt and GBM-IDHm,and in prolonging post-relapse survival for the 2 recurrent GBM subtypes.Conclusions:By controlling for molecular subtypes,we found that resection rate and chemotherapy were 2 prognostic factors associated with survival outcomes in a Chinese cohort with DG.

Exploration of whole brain networks modulated by acupuncture at analgesia acupoint ST36 using scale-specific wavelet correlation analysis

Background Previous studies have demonstrated that acupuncture could modulate various brain systems in the resting brain networks. Graph theoretical analysis offers a novel way to investigate the functional organization of the large-scale cortical networks modulated by acupuncture at whole brain level. In this study, we used wavelets correlation analysis to estimate the pairwise correlations between 90 cortical and subcortical human brain regions in normal human volunteers scanned during the post-stimulus resting state. Methods Thirty-two college students, all right-handed and acupuncture na＇fve, participated in this study. Every participant received only one acupoint stimulation, resulting in 16 subjects in one group. Both structural functional magnetic resonance imaging （fMRI） data （3D sequence with a voxel size of 1 mm3 for anatomical localization） and functional fMRI data （TR=1500 ms, TE=30 ms, flip angle=90°） were collected for each subject. After thresholding the resulting scale-specific wavelet correlation matrices to generate undirected binary graphs, we compared graph metrics of brain organization following verum manual acupuncture （ACU） and sham acupuncture （SHAM） groups. Results The topological parameters of the large-scale brain networks in ACU group were different from those of the SHAM group at multiple scales. There existed distinct modularity functional brain networks during the post-stimulus resting state following ACU and SHAM at multiple scales. Conclusions The distinct modulation patterns of the resting brain attributed to the specific effects evoked by acupuncture. In addition, we also identified that there existed frequency-specific modulation in the post-stimulus resting brain following ACU and SHAM. The modulation may be related to the effects of verum acupuncture on modulating special disorder treatment. This preliminary finding may provide a new clue to understand the relatively function- oriented specificity of acupuncture effects.

Co-transplantation of neural stem cells and Schwann cells within poly （L-lactic-co-glycolic acid） scaffolds facilitates axonal regeneration in hemisected rat spinal cord

Background Various tissue engineering strategies have been developed to facilitate axonal regeneration after spinal cord injury. This study aimed to investigate whether neural stem cells （NSCs） could survive in poly（L-lactic-co-glycolic acid） （PLGA） scaffolds and, when cografted with Schwann cells （SCs）, could be induced to differentiate towards neurons which form synaptic connection and eventually facilitate axonal regeneration and myelination and motor function. Methods NSCs and SCs which were seeded within the directional PLGA scaffolds were implanted in hemisected adult rat spinal cord. Control rats were similarly injured and implanted of scaffolds with or without NSCs. Survival, migration, differentiation, synaptic formation of NSCs, axonal regeneration and myelination and motor function were analyzed. Student＇s t test was used to determine differences in surviving percentage of NSCs. One-way analysis of variance （ANOVA） was used to determine the differences in the number of axons myelinated in the scaffolds, the mean latency and amplitude of cortical motor evoked potentials （CMEPs） and Basso, Beattie ＆ Bresnahan locomotor rating scale （BBB） score. The X2 test was used to determine the differences in recovery percentage of CMEPs. Results NSCs survived, but the majority migrated into adjacent host cord and died mostly. Survival rate of NSCs with SCs was higher than that of NSCs without SCs （（1.7831±0.0402）% vs. （1.4911±0.0313）%, P 〈0.001）. Cografted with SCs, NSCs were induced to differentiate towards neurons and might form synaptic connection. The mean number of myelinated axons in PLGA＋NSCs＋SCs group was more than that in PLGA＋NSCs group and in PLGA group （（110.25±30.46） vs. （18.25±3.30） and （11.25±5.54）, P 〈0.01）. The percentage of CMEPs recovery in PLGA＋NSCs＋SCs group was higher than in the other groups （84.8% vs, 50.0% and 37.5%, P 〈0.05）. The amplitude of CMEPs in PLGA＋NSCs＋SCs group was higher than in the other groups （（1452.63±331.70） IJV vs. （428.84±193.01） IJV and （117.33±14.40） μV, P 〈0.05）. Ipsilateral retransection resulted in disappearance again and functional loss of CMEPs for a few days. But contralateral retransection completely damaged the bilateral motor function. Conclusions NSCs can survive in PLGA scaffolds, and SCs promote NSCs to survive and differentiate towards neurons in vivo which even might form synaptic connection. The scaffolds seeded with cells facilitate axonal regeneration and myelination and motor function recovery. But regenerating axons have limited contribution to motor function recovery.

High-frequency stimulation of anterior nucleus thalamus improves impaired cognitive function induced by intra-hippocampal injection of Aβ1-40 in rats

Background The advent of brain stimulation techniques to treat movement disorders and psychiatric diseases has shown potential to decode the neural mechanism that underlies the cognitive process by modulating the interrupted circuit.Here,the present investigation aimed at evaluating the influence of deep brain stimulation of the anterior nucleus thalamus （ANT-DBS） on memory.Methods Thirty-two rats were randomized into phosphate buffer saline （PBS） group （n=8,rats received PBS injections without implantation of electrodes into the ANT）,Alzheimer＇s dementia （AD） group （n=8,rats received Aβ1-40 injections without implantation of electrodes into the ANT）,ANT sham stimulation group （n=8,rats received Aβ1-40 injections with implantation of electrodes into the ANT but without stimulation） and ANT stimulation group （n=8,rats received Aβ1-40 injections with implantation of electrodes into the ANT and stimulation）.A Morris maze test was used for determining the effect of electrical stimulation on cognitive function in rats.The data were assessed statistically with one-way analysis of variance （ANOVA） followed by Tukey＇s tests for multiple post hoc comparisons.Results The data showed that in the training test,PBS group and AD group managed to learn the hidden-platform faster and faster while AD group needed a significantly longer time to reach the platform than PBS group （P ＜0.05）.Meanwhile,ANT stimulation group demonstrated a significantly shorter time to reach the platform （P ＜0.05） compared to the AD group,while there was no significant difference between the ANT sham stimulation group and the AD group （P ＞0.05）.On the probe test,the AD group spent less time （（10.15±2.34） seconds） in the target quadrant than the PBS group （（28.20±2.75） seconds） （P ＜0.05）.And the times of platform-traversing of the AD group （3.35±1.12） significantly decreased compared with the PBS group （8.69±2.87） （P ＜0.05）.However,the times of platform-traversing and the time spent in the target quadrant of the ANT stimulation group significantly increased compared to the AD group （P ＜0.05）,while times of platformtraversing or the time spent in the target quadrant was not significantly different between the ANT sham stimulation group and the AD group （P ＞0.05）.Conclusion Bilateral high-frequency stimulation of the ANT may be useful as a potential therapeutic modality for cognitive dysfunction in AD.

Differential temporal neural responses of pain-related regions by acupuncture at acupoint ST36： a magnetoencephalography study

Background Previous neuroimaging studies primarily focused on the spatial distribution of acupuncture needling stimulation. However, a salient feature of acupuncture was its long-lasting effect. This study attempted to detect the spatial-temporal neural responses evoked by acupuncture at an analgesia acupoint ST36 by using magnetoencephalography. To further verify its functional specificity, we also adopted acupuncture at Pericardium 6 and nonacupoint as separated controls.Methods Forty-two college students, all right-handed and acupuncture naive, participated in this study. Every participant received only one acupoint stimulation, resulting in 14 subjects in one group. Both magnetoencephalography data （151-channel whole-head system） and structural functional magnetic resonance imaging data （3D sequence with a voxel size of 1 mm3 for anatomical localization） were collected for each subject. All processing procedures were performed in BrainStorm Toolbox.Results Acupuncture at ST36 showed a significantly time-varied brain activities with different onset time. Our results presented that acupuncture at different acupoints （or comparing with nonacupoint） can specifically induce neural responses in different brain areas-acupuncture at ST36 can specifically induce the neural responses of pain-inhibition areas, while acupuncture at PC6 can specifically induce the activities of the insula and amygdala.Conclusions In the present study, we attempted to detect the temporal neural responses underlying the functional specificity of acupuncture at ST36, using acupoint belonging to different meridians and non-acupoint with efficacy-irreverent as separate controls. The specific neural substrates involving acupuncture at different acupoints may be related to its functional specificity in clinical settings.

Optimization of transfection efficiency of small interfering RNA in purified human prolactinoma cells

Background Control of hypersecretion of certain hormones is one of the key targets in the treatment of pituitary adenomas. RNA interference has been shown to inhibit protein expression, and thus it may represent a promising method for the treatment of pituitary adenomas. In the present study, transfection efficiency of small interfering RNA （siRNA） was optimized in human prolactinoma cells. Methods First, a method was optimized to extract highly purified human prolactinoma cells in vitro. The extracted cells were verified to retain the physiological features of prolactin （PRL） secretion. Second, three conditions for siRNA transfection were tested by the evaluation of transfectfon efficiency and cell viability. The proper transfection condition was verified for human prolactinoma cells. Third, the siRNA for prolactin was transfected into the human prolactinoma cells, and the suppression of PRL mRNA was evaluated by quantitative real-time reverse transcription-PCR. Results The siRNA of 100 pmol with Lipofectamine 2000 of 5 μl for 1×10^6 cells was proved preferable, with transfection efficiency being 53.3% and cell viability being 69.7%. In the preliminary experiment the siRNA against PRL decreased the mRNA of PRL by 34.0%. Conclusion It is possible to inhibit hormone hypersecretion by RNA interference, that may eventually enable therapeutic siRNA drugs developed.

Leptomeningeal metastasis from central nervous system tumors: A study of classification and stage in the spinal canal of 58 patients

Leptomeningeal metastasis (LM) is caused by the spread of malignant tumor cells into the subarachnoid space.However,classification and staging of LM in the spinal canal is rare in the literature.The authors reviewed the records of 58 Chinese patients with LM for clinical features,neuroimaging,and treatments.Gadolinium-enhanced magnetic resonance imaging (MRI) of brain and spinal cord were performed in all patients.Removal of intracranial tumors was performed in all patients and diagnoses were confirmed by histology.The study group consisted of 58 patients,with 29 cases presenting with intraspinal symptoms.Of the 58,8 patients underwent intraspinal tumor removal,8 received radiotherapy alone,9 received chemotherapy alone,and 34 patients received combined radiochemotherapy.We classified LM into 3 types:type L or leptomeninges LM,is subdivided into 2 subtypes (subtype LI and LII (a,b)),type N or nerve root LM is subdivided into 2 subtypes (subtype NI and NII (a,b)),and type M or mixed-type LM.We also divided LM into stages of I-IV according to the symptoms and the volume of the tumor based on spinal axial MRI.Type LI LM often occurs in patients with intracranial and intraspinal tumors found simultaneously.Patients who receive surgery for intracranial tumors may present with type N LM.Surgery is suitable for patients with NI LM and LIIb LM in stages III-IV,presenting with severe spinal symptoms.The prognosis is better for type N LM than type L LM.