Neuroimage-Based Consciousness Evaluation of Patients with Secondary Doubtful Hydrocephalus Before and After Lumbar Drainage / 神经科学通报·英文版

Hydrocephalus is often treated with a cerebrospinal fluid shunt (CFS) for excessive amounts of cerebrospinal fluid in the brain. However, it is very difficult to distinguish whether the ventricular enlargement is due to hydrocephalus or other causes, such as brain atrophy after brain damage and surgery. The non-trivial evaluation of the consciousness level, along with a continuous drainage test of the lumbar cistern is thus clinically important before the decision for CFS is made. We studied 32 secondary mild hydrocephalus patients with different consciousness levels, who received T1 and diffusion tensor imaging magnetic resonance scans before and after lumbar cerebrospinal fluid drainage. We applied a novel machine-learning method to find the most discriminative features from the multi-modal neuroimages. Then, we built a regression model to regress the JFK Coma Recovery Scale-Revised (CRS-R) scores to quantify the level of consciousness. The experimental results showed that our method not only approximated the CRS-R scores but also tracked the temporal changes in individual patients. The regression model has high potential for the evaluation of consciousness in clinical practice.

Neuroimage-Based Consciousness Evaluation of Patients with Secondary Doubtful Hydrocephalus Before and After Lumbar Drainage / 神经科学通报·英文版

Hydrocephalus is often treated with a cerebrospinal fluid shunt (CFS) for excessive amounts of cerebrospinal fluid in the brain. However, it is very difficult to distinguish whether the ventricular enlargement is due to hydrocephalus or other causes, such as brain atrophy after brain damage and surgery. The non-trivial evaluation of the consciousness level, along with a continuous drainage test of the lumbar cistern is thus clinically important before the decision for CFS is made. We studied 32 secondary mild hydrocephalus patients with different consciousness levels, who received T1 and diffusion tensor imaging magnetic resonance scans before and after lumbar cerebrospinal fluid drainage. We applied a novel machine-learning method to find the most discriminative features from the multi-modal neuroimages. Then, we built a regression model to regress the JFK Coma Recovery Scale-Revised (CRS-R) scores to quantify the level of consciousness. The experimental results showed that our method not only approximated the CRS-R scores but also tracked the temporal changes in individual patients. The regression model has high potential for the evaluation of consciousness in clinical practice.

White Matter Deficits Underlying the Impaired Consciousness Level in Patients with Disorders of Consciousness / 神经科学通报·英文版

In this study, we aimed to (1) identify white matter (WM) deficits underlying the consciousness level in patients with disorders of consciousness (DOCs) using diffusion tensor imaging (DTI), and (2) evaluate the relationship between DTI metrics and clinical measures of the consciousness level in DOC patients. With a cohort of 8 comatose, 8 unresponsive wakefulness syndrome/vegetative state, and 14 minimally conscious state patients and 25 patient controls, we performed group comparisons of the DTI metrics in 48 core WM regions of interest (ROIs), and examined the clinical relevance using correlation analysis. We identified multiple abnormal WM ROIs in DOC patients compared with normal controls, and the DTI metrics in these ROIs were significantly correlated with clinical measures of the consciousness level. Therefore, our findings suggested that multiple WM tracts are involved in the impaired consciousness levels in DOC patients and demonstrated the clinical relevance of DTI for DOC patients.

Application of Brain Network Analysis to the Study of Acupuncture Effect / 上海针灸杂志

Acupuncture therapy is a therapeutic method in traditional Chinese medicine. Its clinical efficacy has widely accepted internationally but its mechanism of action is still unclear. In recent years, more and more researchers began to use brain network analysis to explore the mechanism of action of acupuncture. This article reviews the significance of brain network analysis in the study of acupuncture effect, that is, brain network analysis can effectively assess changes in cerebral function in chronic pain and observe the real therapeutic effect of acupuncture. It also reviews various methods of brain network analysis, including brain functional connectivity (FC) analysis, amplitude of low frequency fluctuations (ALFF) analysis, regional homogeneity (ReHo) analysis, small-world network (SWN) analysis, positron emission computed tomography (PET) and diffusion tensor imaging (DTI); the shortcomings and prospects of brain network analysis in the application of acupuncture. A summary of the newest research advances in the application of brain network analysis to the study of acupuncture effect provides a certain reference for the future scientific study.

Diagnostic analysis of 80 patients with spontaneous internal carotid artery and vertebral artery dissections / 中华神经科杂志

Objective To investigate the most sensitive methods for diagnosing spontaneous internal carotid artery dissection (sICAD) and spontaneous vertebral artery dissection (sVAD) respectively,for the sake of earlier and more accurate diagnosis.Methods Consecutive patients with sICAD and sVAD who visited the Department of Neurology and Radiology,Huashan Hospital Affiliated to Fudan University during 2008-2013 were retrospectively reviewed and the sensitivity of CT angiography (CTA),magnetic resonance T1-weighted fat-suppressed images (MR T1-FS) and digital subtraction angiography (DSA) for the diagnosis of sICAD and sVAD was compared.Results Eighty patients (62 male,18 female; mean age (45.7 ± 11.9) years) were included in the study.There were 99 arterial dissections in total,45 cases of sICAD,52 cases of sVAD and 2 cases of spontaneous middle cerebral artery dissections.The sensitivity of CTA,DSA and MR T1-FS for diagnosing sICAD was 97.5％ (39/40),90.0％ (36/40) and 69.6％ (16/23) respectively,while for sVAD was 89.8％ (44/49),84.6％ (44/52) and 100.0％ (27/27) respectively.Conclusions sICAD and sVAD have significant differences in many aspects including diagnostic strategies.CTA and MR T1-FS seem to be the most sensitive methods for the diagnosis of sICAD and sVAD respectively.Although DSA has been considered as the gold standard for the diagnosis of artery dissection,this imaging technique does not allow analysis of artery wall thickness,thus also has limitations.It is likely that the diagnostic sensitivity will be improved by combining CTA and MR T1-FS.

Exogenous hydrogen sulfide inhibits expression of tissue factor induced by ox-LDL through reducing generation of ROS and inhibiting NF-κB activation in endothelial cells / 中国药理学通报

Aim To investigate the mechanism for the inhibitory effect of hydrogen sulfide on the expression of tissue factor(TF)induced by oxidative low-density lipoprotein(ox-LDL)in endothelial cells.Methods Human umbilical vein endothelial cells (HUVECs ) were treated with 50 mg·L-1 ox-LDL in the absence or presence of different concentrations of NaHS (25 , 50,100 and 200 μmol·L-1 )for 24 h.The mRNA expression and protein content of TF in HUVECs were determined by reverse transcription PCR and ELISA, respectively.The content of intracellular reactive oxy-gen species (ROS)was determined by DCFH,an oxi-dative sensitive fluorescent indicator.The activation of nuclear factor-kappaB (NF-κB)was estimated by its expression in nuclear extracts analyzed by Western blot.Results Ox-LDL induced TF mRNA expression and increased TF protein content in HUVECs.The in-crease in intracellular ROS production and the activa-tion of NF-κB were observed in HUVECs treated with ox-LDL.However,NaHS could markedly inhibit the increases in TF mRNA and protein levels induced by ox-LDL.Also the elevation of intracellular ROS pro-duction and the activation of NF-κB elicited by ox-LDL were significantly suppressed by pretreatment with NaHS.In addition,pretreatment with BAY 1 1-7082 (10 μmol·L-1 ),the inhibitor of NF-κB or N-acetyl-L-cysteine(1 mmol·L-1 ),an antioxidant,could also decrease the TF mRNA and protein level as well as ROS production and NF-κB activation induced by ox-LDL in HUVECs,similar to the effects of 200 μmol· L-1 NaHS.Conclusion The mechanism for the in-hibitory effect of H2 S on the ox-LDL- induced TF ex-pression in endothelial cells may be related to inhibi-ting intracellular ROS production and subsequently NF-κB activation.

Aberrant resting-state functional connectivity of default mode and salience network in patients with schizo-phrenia / 中国神经精神疾病杂志

Objective To explore the feature of functional connectivity of default mode network (DMN) and salience network (SN) in unmedicated schizophrenia patients during a resting state by functional magnetic resonance imaging (fM-RI). Methods The SPM8 and DPARSFA softwares combined with independent component analysis (ICA) were used to in-vestigate functional connectivity (FC) of the DMN and SN in 27 unmedicated patients with schizophrenia and 27 age-and gender-matched healthy controls. Results Concerning the DMN, patients with schizophrenia showed decreased FC in right inferior frontal gyrus , right precuneus(unadjusted P<0.05)and increased FC in right middle cingulate gyrus, left middle frontal gyrus(unadjusted P<0.05). With regard to the SN, patients showed reduced connectivity in left inferior frontal gyrus, right inferior frontal gyrus, left anterior cingulate, left postcentral gyrus(unadjusted P<0.05)and increased connectivity in left superior temporal gyrus(unadjusted P<0.05). Correlation analyses showed that the increased FC of left superior temporal gyrus significantly correlated with PANSS-positive symptoms(r=0.568,P=0.002)and decreased FC of right precuneus significantly negatively correlated with delusion symptom(r=-0.458,P=0.016). Conclusion This study provides evidence for resting state functional abnormalities of DMN and SN in unmedicated schizophrenia patients. These aberrant function connectivities in some brain regions of the two networks could be a source of abnormal introspectively-oriented mental actives.

miR-216a suppresses cell proliferation and invasion by targeting PRKCA in glioma / 中国癌症杂志

Background and purpose: MicroRNAs are 19–25-nucleotide noncoding RNA molecules that regulate gene expression at the level of transcription and translation. The study aimed to confirm whether miR-216a suppresses cell proliferation and invasion by targeting PRKCA, thus to reveal molecular mechanism that miR-216a functions as a tumor suppressor in glioma. Methods: PRKCA 3’ untranslated region (UTR)-luciferase vector was constructed and dual-luciferase reporter gene assay was employed to examine the effect of miR-216a on luciferase activity. U251 cells were transfected with miR-216a mimics, and next Western blotting was performed to detect the expression of PRKCA protein. The effects of PRKCA downregulation on cell proliferation and invasion were observed after PRKCA siRNA was transfected into U251 cells. U251 cell proliferation assays were performed when cotransfected with miR-216a mimics. Results:The result demonstrated miR-216a could bind to the 3’UTR of PRKCA and inhibited the luciferase activity by 41%. PRKCA protein expressions were significantly down-regulated when miR-216a was overexpressed in U251. siRNA-mediated downregulation of PRKCA could suppress the potentials of cell proliferation and invasion. Conclusion:miR-216a suppresses cell proliferation and invasion by targeting PRKCA in glioma.

Chinese herbal medicine for patients with mild to moderate Alzheimer disease based on syndrome differentiation: a randomized controlled trial / 中西医结合学报

Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by its gradual progression. At present, the cause and mechanism of AD are yet unclear, and there is no effective therapy for treating it. With development of global aging, the prevalence rate of AD is increasing. The life quality of elderly people is affected severely by AD that is ultimately life-threatening. Recently, study on treating AD with traditional Chinese medicine (TCM) has deepened.

A pilot fMRI study of event-based prospective memory in healthy adults / 中华行为医学与脑科学杂志

ObjectiveTo investigate the neural mechanism of prospective memory(PM) using functional magnetic resonance imaging (fMRI).MethodsFifteen healthy volunteers were enrolled,and all subjects were scanned with fMRI while performing the event-based PM tasks (double-task paradigm,including the ongoing task and PM task).And the image data were preprocessed and analyzed by using SPM8 software.Results ( 1 ) Compared to the control task,bilateral rostral prefrontal cortex ( x,y,z =6/- 2,54/42,- 8/- 12,t =3.71 ),right somatosensory association area ( x,y,z =14,- 62,64,t =4.64 ),superior temporal gyrus ( x,y,z =42,- 46,16,t =3.95 ) and right paracentral lobule (x,y,z =10,-22,76,t =4.01 ) were activated significantly by the ongoing task (P ＜ 0.001 ).(2) Bilateral rostral prefrontal cortex ( x,y,z =- 2/6,42/54,- 12/- 12,t =3.28) and paracentral lobule (x,y,z =- 30/10,- 22/- 22,72/76,t =4.25 ),left postcentral gyrus ( x,y,z =- 38,- 46,64,t=3.13) and middle occipital gyrus ( x,y,z =- 30,- 70,0,t =3.97 ) were activated significantly by the PM task (P ＜ 0.001 ).ConclusionRostral prefrontal cortex (BA 10 area) is the major area of prospective memory,and medial BA10 area may be involved in the monitoring of external cues.The present study supports the gateway hypotheses of prospective memory.

Pancreatic tuberculosis: MDCT features and differential diagnosis / 中华胰腺病杂志

Objective To study the multi-detector spiral CT (MDCT) features of pancreatic tuberculosis to improve the awareness and correct diagnosis. Methods Imaging features of MDCT were retrospectively reviewed on 9 cases with pancreatic tuberculosis that were diagnosed from 2003 to 2009, among them two patients underwent MDCT angiography, the features were compared with those of operative and pathological findings. Results One case of pancreatic cancer, 2 cases of cystadenocarcinoma and 1 case of pseudocyst, 2 cases of pancreatic cancer with retroperitoneal lymph node metastasis, 2 cases of lymphoma were diagnosed by MDCT, and all the lesions were diagnosed as pancreatic tuberculosis pathologically, and the misdiagnosis rate was 100%. Pancreatic tuberculosis often presented as pancreatic head mass, sometimes pancreatic body and tail were involved. MDCT showed isopycnic or low density solid-cyst mass, occasionally calcification was present, with slightly or moderate ring-like enhancement after contrast injection. There was no enlargement of the pancreatic duct. The retroperitoneal and adjacent lymph nodes were always enlarged with ring-like enhancement. Sometimes there was evidence of tuberculosis of other abdominal organs. Conclusions Ring-like enhanced lesions with ring-like enhanced lymph nodes without enlargement of pancreatic duct are characteristic MDCT features of pancreatic tuberculosis.

Clinical Observation On The CPT-11 Plus 5-FU For treatment Advanced Rectal Cancer / 中国基层医药

Objective To evaluate the efficacy and adverse events of irinotecan (CPT-11) combined with 5-FU in treatment of patients with advanced rectal cancer. Methods 86 patients were randomly divided into FOLFIRI treatment group and IFL treatment group. The efficacy and adverse events were observed. Results There was no statistically significant difference between FOLFIRI treatment group and IFL treatment group in CR、PR、SD and RR(all P ＞ 0. 05). There was also no statistically significant difference between FOLFIRI treatment group and IFL treatment group in adverse events(all P ＞ 0.05). Conclusion Irinotecan in combination with 5-FU was effective and had some tolerable adverse events in treating patients with advanced rectal cancer in both FOLFIRI treatment group and IFL treatment group.

MR diffusion tensor imaging voxel-based analysis of whole brain white matter in patients with amnestic-type mild cognitive impairment and mild Alzheimer disease / 中华放射学杂志

Objective To evaluate the microstructural integrity of white matter (WM) in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD) using voxel-based analysis (VBA), and investigate the relationship between WM abnormalities and gray matter(GM) atrophy.Methods Thirty-three cases with aMCI, 32 cases with mild AD and 31 normal aging volunteers as control subjects were scanned on a 3.0 T MR system using diffusion tensor imaging (DTI) and three-dimensional spoiled gradient-recalled(3DSPGR) sequences. Fractional anisotropy (FA) maps and morphological images were preprocessed by SPM5 and voxel-based comparisons between the 2 patient groups and the control group were performed by t test. Results Relative to the control group, patients with aMCI showed significantly reduced FA value in bilateral frontal, temporal and left occipital WM, left anterior part of cingulum, left inferior parietal lobule, and the W M adjacent to the triangular part of the right lateral ventricle(k≥20 voxels).In mild AD,significantly reduced FA value was found in bilateral hippocampal,inferior parietal lobular,frontal,temporal,and occipital WM,bilateral corpus callosum,anterior part of cingulums,the WM adjacent to the triaangular part of the bilateral lateral ventricles,left temporal stem,left thalamus,right precuneus(k≥20 voxels).Significantly reduced GM volume was found in left hippocampus,parahippocampal gyrus,lingual gyrus and superior temporal gyrus,bilateral insulae and middle temporal gyri in aMCl group whencompared with control group(k≥50 voxels).In mild AD,significantly reduced GM volume was found in bilateral hippoeampi,parahippocampal gyri,amygdalae,thalami,temporal,parietal,frontal,occipital cortex(k≥50 voxels).The pattern of areas with reduced FA differs;from that of the GM volumetric reduction.No areas with significantlv reduced FA was detected in aMCl compared with mild AD. There was no significant correlation between FA value of WM in patient groups and Mini-Mental State Examination(MMSE)scores.Conclusions Voxel-based MRI DTI analysis of whole brain white matter can objectively reveal widespread white matter abnormalities in early-stage AD.The difierence between WM FA reduction pattern and GM volumetric reduction pattern indicates that the pathological WM changes in earlyslage AD were caused by multiple mechanisms. FA did not vary significantly in patients pr0gressing from aMCI to mild AD and can hardly reflect the severitv of cognitive function damage in these patients.

Functional MRI for patients with visual pathway diseases / 中华眼底病杂志

Objective To observe the results of function MRI and perimetry in patients with visual pathway diseases. Methods Three patients (6 eyes) with pituitary adenoma and craniopharyngioma diagnosed via pathological examination and three healthy volunteers aged from 24 to 30 were collected. The best corrected visual acuity was non-light perception-1. 0 in the 6 sick eyes and 1. 0 in the healthy eyes;all the involved individuals had no other ocular diseases except myopia and without any contraindications of MRI. Common tests including the best visual acuity, fundus test by direct or indirect ophthalmoscope, center static visual field tested by Octopus 101 perimeter, program 32, tendency oriented perimetry were performed. The visual stimulation subtended a field of view of about 12 degrees,consisted of high contrast and drifting checkerboards. MRI parameters: GE signa VH/i 3. 0T scanner. Functional data: GRE-EPI sequence, 20 slices lying perpendicular to the calcarine sulcus. Anatomical data was obtained using 3DSPGR sequence to acquire high resolution. The cortical surface was unfolded and then cut and inflated. Functional data was presented to the inflated surface and subsequently analyzed by AFNI software. Results In six eyes, three had temporal defects, two had upper temporal visual field defects, and the other one did not finish the visual field test. The retinotopic representations of health adults were obtained by using the phase-encoded visual stimulation. The Eccentricity coordinate maps showed that foveal representations lay in the occipital poles and the representations appeared further anterior as eccentricity increased. The polar angle coordinate maps showed that early retinotopically organized areas had a representation of visual field. The visual cortex beneath the calcarine sulcus matched with the upper visual field of the opposite side and which upon the calcarine sulcus matched with the under visual field of the opposite side. Less or no visual cortex response was revealed in the patients' function MRI or the response in injury side was vanished. The visual cortex response related with the visual field defects could not be induced in function MRI. Conclusion There is a good correlation between function MRI data and the results of perimetric evaluation. The function MRI can show the visual cortex response correlated with the visual field defects of the patients with visual pathway diseases.

Cerebral activation during Chinese semantic associative task in Xinjiang' Uyghurs: a functional MRI study / 中华放射学杂志

Objective To explore the cerebral activation in Xinjiang' Uyghurs when performing a Chinese word tasks by the functional magnetic resonance image (fMRI).Methods Twenty-one healthy Xinjiang' Uyghurs and 11 healthy Hans were scanned using functional magnetic resonance imaging (fMRI) on a 1.5 T MRI scanner with a single run.Different Chinese words were displayed in each block to avoid any practice effect SPM5.0 software was used for image data processing.To evaluate the inter subject consistency of brain activations associated with Chinese character and word reading, we created penetrance maps by combining binary individual functional maps.Results For Uyghur-Chinese bilingual subjects, activations related to generated a word that was semantically related to each stimulus.The results indicated that reading Chinese is characterized by extensive activity of the neural systems.Peak activations occurred in the left middle frontal cortex at Brodmann Areas (BA9 and BA 47).The left temporal (BA 37) cortices were also strongly activated.Other important activated areas included bilateral visual systems (BA 17-19) and cerebellum.The location of peak activation in the left frontal regions was similar in Native Uyghurs and Hans.But the active areas in Uyghurs are more extensive than that of Hans .Conclusions The location of peak activation in the left frontal regions was similar in Native Uyghurs and Hans.More brain areas were needed for Xinjiang' Uyghur speakers during processing Chinese words.

A comprehensive application research of multi b value diffusion weighted imaging / 生物医学工程学杂志

This research introduces a new method to analyze the diffusion information of human brain. By use of the multi b value diffusion data and a new algorithm, a new diffusion parameter (Rd) was computed, and a new image was reconstructed. Through quantitative research on the brains of 25 normal adults, the new method can improve the signal-to-noise ratio (SNR) apparently and distinguish the different brain tissues effectively, compared to the apparent diffusion coefficient. The new method can improve the sensitivity to diffusion.

Clinical value of 64-row CT angiography in detection of carotid atherosclerotic plaque / 中华全科医师杂志

Objective To explore clinical significance of muhidetector(64-row)computed tomography carotid atherosclerosis angiography(MDCTA)in detecting carotid atherosclerotic plaque.Methods Data of 116 patients with carotid atherosclerosis undergone with MDCTA stayed at Huashan Hospital,Shanghai from January to August,2008 were analyzed retrospectively.Results Three hundred and seventy-seven plaques were identified among all the 116 patients in the study,with an incidence of calcified plaque of 63.40 percent,and more detected at the common carotid artery(27.85%).the carotid bifurcation(39.78%)and the internal carotid artery (21.48%).There was significantly statistical difference in plaque types between those with mild,moderate and severe carotid stenosis(P=0.000)and between those aged equal to or lower than 50 years and equal to or greater than 70 years(P=0.005).Plaque types at the common carotid artery were significantly difierent from those at the carotid bifurcation(P=0.000)and at the internal carotid artery(P=0.000).Results of regression analysis showed a positive and significant association between carotid occlusion and clinical symptomatology(with a coefficient of correlation of 1.080.P=0.023)and inverse association between calcified plaque and clinical symptomatology(with a coefficient of correlation of 0.688,P=0.006).Conclusions Not only imaging characteristics of carotid atherosclerotic plaque can be accurately assessed by MDCTA,but also measurement of its stenosis degree.Assessment of plaque type,degree of stenosis and distribution of plaque in different Vascular segments with MDCTA can be used to predict clinical occurrence of cerebevaseular events in patients with carotid atherosclerosis.

Medical image retrieval by high level semantic features and low level content features of image / 生物医学工程学杂志

Content-based image retrieval aims at searching the similar images using low level features,and medical image retrieval needs it for the retrieval of similar images. Medical images contain not only a lot of content data, but also a lot of semantic information. This paper presents an approach by combining digital imaging and communications in medicine (DICOM) features and low level features to perform retrieval on medical image databases. At the first step, the semantic information is extracted from DICOM header for the pre-filtering of the images, and then dual-tree complex wavelet transfrom(DT-CWT) features of pre-filtered images and example images are extracted to retrieve similar images. Experimental results show that by combining the high level semantics (DICOM features) and low level content features (texture) the retrieval time is reduced and the performance of medical image retrieval is increased.

Expression of vitamin D receptor in rectal carcinoma and mucosa adjacent to carcinoma / 中国普通外科杂志

Objective To evaluate the expression of vitamin D receptor (VDR) in rectal cancer and mucosa adjacent to cancer. Methods The VDR expression of tumor tissue,mucos a 2cm apart from tumor and normal mucosa was detected by imunohistochemistry, mi crospectrophotometer and computer image analysis in 21 cases of rectal carcinoma . Results The VDR expression in rec tal tumor (2.4?0.7) significantly decreased compared to that of the norma l mucosa (6.0?0.6)(P

Functional magnetic resonance imaging of schizophrenic patients and comparison subjects during a verbal fluency task / 中华放射学杂志

Objective To study the changes in cortical activation of frontal lobes and temporal lobes between schizophrenic patients and comparison subjects during a verbal fluency task by using functional magnetic resonance imaging (fMRI). Methods Thirteen schizophrenic patients and 8 volunteers were studied during a verbal fluency task performance. fMRI of frontal lobes and temporal lobes was conducted at a GE 1.5 T Signa Horizon LX scanner while the subjects performed the task. Stimulus sequences were divided into six 30-second segments by using a task-activation paradigm that alternated between resting and stimulated states. Results Schizophrenic subjects demonstrated significantly less left frontal activation than comparison subjects during a word fluency task, and comparison subjects showed evidently more activation in left frontal lobes than in the right (P0.05). Conclusion These preliminary data suggest that fMRI has the sensitivity to detect the differences in activation between comparison subjects and schizophrenic patients during higher cortical functions.