1.Correlation between change in choroid plexus volume and cognitive function in patients with Parkinson's disease
Suyi ZHOU ; Zhiming ZHEN ; Huilin PANG ; Zhi LIU ; Yanhui LIU ; Wei CHEN ; Wei CHEN
Journal of Army Medical University 2025;47(7):649-655
Objective To investigate the change in choroid plexus(CP)volume in Parkinson's disease(PD)patients with different cognitive states and its correlation with structural volumes of other brain regions.Methods A cross-sectional study was conducted on 48 PD patients admitted in Department of Neurosurgery of the First Affiliated Hospital of Army Medical University between May 2023 and April 2024,and on 35 healthy controls(HC)recruited through a physical exam center.According to the results of Mini-Mental State Examination(MMSE),the patients were divided into PD with cognitive impairment(PD-CI)group(n=27)and PD with normal cognitive function(PD-NC)group(n=21).3.0T magnetic resonance imaging(MRI)was performed using MPRAGE sequences,and CP volume and volumes of other brain regions were obtained using FreeSurfer 6.0 software.The CP volume was adjusted by calculating the ratio of its volume to estimated total intracranial volume(eTIV).After controlling for confounders,partial correlation analysis was used to assess the relationship between the CPV/eTIV ratio and the volumes of other brain regions as well as cognitive scale scores.Additionally,multiple linear regression analysis was performed to further explore the relationship between CPV and cognitive function in the PD-CI group.Results Compared to the HC group,the CPV in the PD-CI group was significantly larger(P=0.029).In the PD-CI group,the CPV/eTIV ratio showed significant positive correlations with the volume of the lateral ventricles(r=0.689,P=0.001),the volume of the third ventricle(r=0.592,P=0.006),the volume of cerebrospinal fluid(CSF)(r=0.508,P=0.022),and white matter hyperintensities(WMH)(r=0.486,P=0.030),but was negatively correlated with the volume of the caudate nucleus(r=-0.530,P=0.016),the volume of the thalamus(r=-0.477,P=0.033),and the MMSE scores(r=-0.483,P=0.031).But in the PD-NC group,the CPV/eTIV ratio was only positively correlated with CSF volume(r=0.571,P=0.021).Multiple linear regression analysis indicated that the CPV/eTIV ratio and MMSE scores remained significantly negatively correlated in the PD-CI group(β=-0.388,P=0.046).Conclusion Cognitive impairment in PD patients may be closely associated with the change in CP volume,suggesting that the volume can serve as a potential imaging marker in assessment of cognitive impairment in PD patients.
2.Changes in choroid plexus volume in healthy adults during natural ageing
Huilin PANG ; Zhiming ZHEN ; Meng ZENG ; Suyi ZHOU ; He LIU ; Wei CHEN ; Wei CHEN
Journal of Army Medical University 2024;46(22):2547-2553
Objective To investigate age-and sex-related changes in choroid plexus(CP)volume in healthy adults,as well as its association with the volumes of other brain regions,and explore the relationship of CP volume changes with degenerative brain alterations.Methods A total of 320 healthy subjects aged between 18 and 85 years were prospectively recruited in Physical Examination Center of First Affiliated Hospital to Army Medical University during August 2023 and February 2024.These participants were randomly divided into 7.OT and 3.OT groups,with 160 people in each group.After all of them underwent sagittal three-dimensional structural MPRAGE scans of magnetic resonance imaging(MRI)at 3.OT or7.OT,FreeSurfer 6.0 segmentation software was employed to obtain the volumes of CP and other brain regions automatically.Spearman analysis was applied to analyze the correlation of CP volume with age.Independent sample t-test analysis was applied to analyze the differences in CP volume between genders.Partial correlation analysis was performed to analyze the correlation between CP volume and the volumes of other brain regions.Results A total of 311 subjects were included in the study.The results from both 3.OT and 7.OT MRI showed that CP volume was positively correlated with age(3.OT:r=0.462,P<0.001;7.OT:r=0.539,P<0.001).The males had significantly larger CP volume than the females(3.OT:1.4±0.47 vs 1.08±0.39 mL,P<0.001;7.OT:2.43±0.68 vs 1.98±0.38 mL,P<0.001).In addition,3.OT MRI revealed there was a significant positive correlation of CP volume with the volumes of white matter hyperintensities(WMH)and cerebrospinal fluid(P<0.001),as well as a negative correlation with the volumes of gray matter,white matter,hippocampus and thalamus(P<0.05).Conclusion CP volume is increased with ageing,with gender differences,independent of field strength and resolution.CP volume is correlated with WMH,hippocampus and other brain regions,suggesting that increment in CP volume is involved in age-related degenerative changes in the brain.Changes in CP volume might be regarded as a new imaging marker for the neurodegenerative changes.
3.Quantitative MRI research on the correlation between the glymphatic system and motor dysfunction in spinocerebellar ataxia type 3
Peiling OU ; Zhiming ZHEN ; Yonghua HUANG ; Lihua DENG ; Linfeng SHI ; Jiaojiao WU ; Rui HUA ; Feng SHI ; Jian WANG ; Chen LIU
Chinese Journal of Radiology 2024;58(12):1396-1401
Objective:To investigate alterations in the glymphatic system of spinocerebellar ataxia type 3 (SCA3) patients based on quantitative MRI, and its association with genetic information and motor dysfunction.Methods:The study was a cross-sectional study. This prospective study recruited 39 confirmed SCA3 patients (SCA3 group) and 40 matched healthy controls (HC group) who were seen at the Southwest Hospital of Army Medical University from May 2017 to June 2023. All subjects underwent cranial MRI scanning. Clinical assessments were conducted on all participants using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). The automatic segmentation and volume measurement of the choroid plexus based on Freesurfer 6.0; the perivascular interstitial space (PVS) was automatically segmented based on the deep-learning model VB-Net, and the volume of the PVS in each brain region was quantified after manual correction. Independent samples t-test and Mann-Whitney U-test were used to analyze the changes in the class lymphatic system in the SCA3 group and the HC group. Pearson partial correlation analysis was used to explore the relationship between CAG repeats, the glymphatic system, and motor dysfunction. Results:The standardized choroid plexus volume in the SCA3 group was (1.24±0.36)×10 3 mm 3, and that in the HC group was (0.96±0.34)×10 3 mm 3, with a statistically significant difference ( t=4.01, P<0.001). PVS volumes in the frontal lobe, temporal lobe, parietal lobe, basal ganglia, cerebellum, thalamus, and brainstem regions in the SCA3 group were significantly higher than those of HC group ( P<0.05). Partial correlation analysis revealed that CAG repeats in SCA3 group were positively correlated with SARA, ICARS, and basal ganglia PVS volumes ( r=0.65, 0.58, 0.29; P=0.001, 0.001, 0.042). Cerebellar and temporal lobe PVS volumes were positively correlated with SARA ( r=0.59, 0.47; P=0.001, 0.003), and positively correlated with ICARS scores ( r=0.61, 0.40; P=0.001, 0.011). Choroid plexus volume was positively correlated with cerebellar and basal ganglia PVS volumes ( r=0.41, 0.31; P=0.009, 0.043). Conclusions:The glymphatic system of SCA3 patients have significant alteration and have association with CAG repeats and motor dysfunction.
4.Clinical characteristics and genetic analysis of a pedigree with Stargardt disease caused by a novel mutation in ABCA4 gene
Rongrong WANG ; Jingwen LIU ; Jingyu MA ; Qingjie ZHEN ; Zhiming LU ; Xiaohui BAI
Chinese Journal of Laboratory Medicine 2022;45(12):1219-1226
Objective:To explore the clinical characteristics and genetics of a pedigree with Stargardt disease, and investigate the pathogenicity of ABCA4 (ATP binding cassette subfamily A member 4) gene mutations in Stargardt disease.Methods:The proband was admitted to the Second People′s Hospital of Jinan in May 2021 due to diminution of vision. The proband was diagnosed with Stargardt disease according to the clinical diagnostic criteria of Stargardt disease. Detailed ophthalmological examinations was also performed on family members of the proband. Genomic DNA were extracted from the proband and the family members, and the whole exon sequencing was performed to find pathogenic gene mutations. The hazard of mutations was analyzed by polyphen-2, SIFT and MutationTaster websites. Sanger sequencing was used to verify the mutations. Conserved analysis of homologous species and 3-dimensional (3D) molecular model of the protein were used to analyze the pathogenicity.Results:Ophthalmological examinations showed reduced binocular vision, macular atrophy and "bull′s eye sign" in the proband and there was no abnormal signs and symptoms among the family members. Through whole exon sequencing analysis and Sanger sequencing verification, the compound heterozygous mutations (c.215G>A and c.6563T>C) of ABCA4 gene were co-segregated with this disease in this family. SIFT, Polyphen-2 and MutationTaster predicted that these two mutations were pathogenic. Conservative analysis and 3D molecular model of protein showed that mutations could cause changes in protein structure and affect protein function.Conclusion:The compound heterozygous mutations (C.215G>A and C.6563T>C) of ABCA4 gene are the pathogenic mutations of Stargardt disease in this pedigree.
5.Kaposi sarcoma after kidney transplantation: a case report and literature review
Kun LI ; Zhiming WANG ; Zhen ZHANG ; Kai WANG ; Guangjian WANG ; Fengfu GUO
Chinese Journal of Organ Transplantation 2018;39(10):606-609
Objective To investigate the epidemiology,clinical features,etiology and treatment of Kaposi sarcoma after kidney transplantation through the diagnosis and treatment of a patient with Kaposi sarcoma after kidney transplantation.Methods The clinical data of a 61-year-old man with Kaposi sarcoma who had kidney transplantation in 2015 were retrospectively analyzed,and the relevant leteratures at home and abroad were reviewed.The patient was an elderly male who underwent renal allograft transplantation for end-stage uremia,and the operation was successful.Preoperative detection of antibodies such as EB virus were negative.Besides,the donor donated organs after the death of the citizen (donation after cardiac death).The man developed dark brown plaques on the outside of his right lower leg and had a roundish-purple tumor on his left ear at the end of 3 months after kidney transplantation,gradually increasing without any other special discomfort.After admission,relevant examinations showed that the function of the transplanted kidney was stable and no other related lesions were found.HIV confirmatory test was negative and the pathology was consistent with Kaposi sarcoma.Therefore,the diagnosis was Kaposi sarcoma and kidney transplantation status.Results Then,the treatment was modified.The cyclosporine +mycophenolate mofetil + prednisone triple immunosuppressive regimen was discontinued and the immunosuppressive drug was changed to sirolimus at a concentration of about 5.69 ng/mL.After treatment for half a year,the Kaposi sarcoma disappeared gradually.Furthermore,the graft function was still stable and up to now,no recurrence of Kaposi sarcoma has been observed.Conclusion Though characteristics of skin lesion are helpful,confirmed diagnosis relies on pathology.And sirolimus may be effective in the treatment of Kaposi sarcoma after kidney transplantation.
6.Abnormal expression and its regulation mechanism of Cav-1 gene in gastric cancer
Yanli GUO ; Zhen ZHOU ; Wei GUO ; Gang KUANG ; Zhibin YANG ; Zhiming DONG
Chinese Journal of Clinical and Experimental Pathology 2015;(3):255-259
Purpose To investigate the expression of Cav-1 in gastric cancer ( GC) cell lines and GC samples, and to analyze the pos-sible effect of gene methylation in expression of Cav-1. Methods Methylation specific PCR ( MSP) method was applied to examine the CpG methylation of the Cav-1 promoter in GC cell lines (AGS, MKN45, BGC-823) and 104 samples of GC and corresponding ad-jacent tissues. RT-PCR method was applied to examine the mRNA expression in GC cell lines. IHC were applied to examine the pro-tein expression of Cav-1 in the GC tissues. Results The expression level of Cav-1 mRNA was obviously increased after treated with 5-aza-2’-deoxycytidine (5-Aza-Dc, a demethylation agent) in AGS cell line. We detected the positive expression of Cav-1 gene in MKN45 and BGC-823 cell lines before and after treated with 5-Aza-Dc. The level of Cav-1 mRNA expression was no any change in AGS, MKN45 and BGC-823 cell lines treated with trichostatin A (TSA). MSP results showed that it can be amplified methylated bands in AGS cell line, and the methylated bands disappeared after treated with 5-Aza-Dc. MKN45 and BGC-823 cell lines were no any methylated bands amplified before and after treatment. The methylation frequency of Cav-1 gene was 29. 8% (31/104), which was significantly higher than that in adjacent tissues (P=0. 000). Furthermore, Cav-1 gene hypermethylation status was correlated with lymph node metastasis and family history of upper gastrointestinal cancers ( UGIC) , but not with pathological grade and clinical stage (P>0. 05). The positive frequency of Cav-1 expression was 51. 9%(54/104) in GC, which was significantly lower than that in adja-cent tissues (P=0. 000). The expression of Cav-1 was correlated with the frequency of gene methylation in GC tissues (P=0. 000). Conclusion The expression of Cav-1 was reduced in GC tissues and the gene hyermethylation may be one of the mechanisms causing Cav-1 gene silencing.
7.Changes of plasma levels of soluble VEGFR2 and SOD in hypertensive patients and hypertensive diabetic patients
Shujie YU ; Bin ZHOU ; Zhiming SONG ; Yong LIU ; Baoshun HAO ; Min WANG ; Zhen WU ; Lin CHEN ; Xiaoxian QIAN ; Jieming ZHU
Chinese Journal of Pathophysiology 2015;(5):797-801
AIM:To explore the changes of plasma levels of soluble vascular endothelial growth factor receptor 2 ( sVEGFR2) and superoxide dismutase ( SOD) in hypertensive patients and hypertensive diabetic patients.METHODS:In this cross-sectional study, 88 cases were enrolled, which were divided into hypertensive group (n=31), hypertensive diabetic group ( n=31 ) and control group ( n=26 ) .Blood pressure was obtained from each participant with mercury sphygmomanometer.The levels of sVEGFR2 and SOD were measured by ELISA.Meanwhile, the levels of plasma glucose, glycosylated hemoglobin A1c ( GHbA1c) and lipid profile were detected.RESULTS:The levels of total cholesterol ( TC) and body mass index (BMI) were significantly higher in hypertensive group than those in control group (P<0.05).The levels of TC, low-density lipoprotein cholesterol ( LDL-C) , triglyceride ( TG) , BMI, waist circumference were significantly higher in hypertensive diabetic group than those in control group (P<0.05).The plasma levels of sVEGFR2 and SOD in both hypertensive diabetic group and hypertensive group were significantly decreased compared with control group ( P<0.05), while the mean plasma levels of sVEGFR2 and SOD in hypertensive diabetic group were significantly decreased compared to the hypertensive group ( P<0.05 ) .A significantly positive correlation between sVEGFR2 and SOD in the whole study population (P<0.05) was observed.CONCLUSION: The plasma level of sVEGFR2 is decreased in both hypertensive and hypertensive diabetic patients, and more significantly decreased in hypertensive diabetic patients.De-creased SOD level may be associated with to the reduction of sVEGFR2.
8.Expression and methylation status of CAV-1 gene in esophageal squamous cell carcinoma
Zhen ZHOU ; Yanli GUO ; Lijie HAN ; Wei GUO ; Shumei LI ; Supeng SHEN ; Zhiming DONG
China Oncology 2014;(10):789-793
Background and purpose: As one of the important epigenetic phenomena, DNA methylation plays an important regulatory function for the expression of genes. Study shows that abnormal changes of DNA methy-lation patterns of normal tumor cell genome leads to dysfunction of cancer related gene, and this may be associated with tumor occurrence and development. The study investigated the promoter methylation and expression of caveolin-1 (CAV-1) gene in esophageal squamous cell carcinoma (ESCC), and to elucidate its role in ESCC. Methods:We used MSP approach, RT-PCR, and immunohistochemistry method respectively to examine the methylation status of the 5’CpG island of CAV-1 gene and its expression at mRNA and protein levels in tumors and corresponding normal tissues. Results: CAV-1 mRNA expression in tumor tissues (0.86±0.56) was signiifcantly higher than that in corresponding normal tissues (0.40±0.36, P<0.05). The mRNA expression of CAV-1 was correlated with status of lymphatic metastasis and TNM stage of ESCC patients (P<0.05). The protein expression of CAV-1 in tumor specimens (66.7%, 34/51) was signiifcantly higher than that in corresponding normal tissues (15.7%, 8/51, P<0.01). The protein expression of CAV-1 was signiifcantly associated with lymphatic metastasis of ESCC (P<0.05), however, it was not associated with differen-tiation and TNM stage (P>0.05). The promoter methylation frequency of CAV-1 in tumor specimens was 2.0%(1/51), and the methylation phenomenon has not been found in corresponding normal tissues. The promoter methylation fre-quency of CAV-1 in tumor specimens showed no signiifcant difference compared with the corresponding normal tissues (P>0.05). Conclusion:The mRNA and protein expression of CAV-1 in tumor specimens was signiifcantly higher than that in corresponding normal tissues. Aberrant high expression of CAV-1 has played a certain role in promoting tumori-genesis and lymph node metastasis. The expression both in ESCC and corresponding normal tissues has no correlation with the promoter methylation status.
9.Effects of exclusive enteral nutrition on the mucosal healing in adult patients with active Crohn's disease
Zhen GUO ; Weiming ZHU ; Jianfeng GONG ; Wei ZHANG ; Zhiming WANG ; Ning LI ; Jieshou LI
Chinese Journal of Digestion 2013;33(12):831-834
Objective To explore the effects of exclusive enteral nutrition (EEN) on the mucosal healing under endoscopy in adults with active Crohn's disease (CD).Methods From August 2011 to August 2012,adults with active CD met the inclusion criteria were prospectively enrolled and treated with EEN for four weeks.CD activity index(CDAI) score,C-reactive protein (CRP) were evaluated once enrolled and by the end of the second and fourth week.Colonoscopy or small intestinal endoscopy examination was conducted once enrolled and by the end of fourth week,and CD simplified endoscopic score (SES-CD) was also caculated.Wilcoxon test was applied to compare the efficacy.Results Eight patients met inclusion criteria and finished the study.Seven cases achieved clinical remission.Compared with those before treatment,both CDAI score and CRP level decreased significantly after treatment (both Z=2.52,both P=0.012).After treatment,two patients achieved mucosal healing and the mucosa of six cases improved.The mucosa healing rate and improvement rate of terminal ileum was higher than that of colon (3/8 vs 1/6; 5/8 vs 3/6).Compared with those before treatment,SES-CD total score and SES-CD score of ileum decreased significantly after treatment (Z=2.23,2.07; P=0.026,0.038).There was no significant difference in SES-CD score of colon before and after treatment (P =0.102).Conclusions EEN could induce clinical remission in adults with active CD,and promote the healing of mucosal ulcer under endoscopy.The healing rate of colon was lower than that of small intestine.
10.Experimental research on the compatibility of self-assembly nanofiber hydrogel from the amphipathic peptide containing IKVAV with olfactory ensheathing cells of rats.
Leyin ZHU ; Zhiming CUI ; Guanhua XU ; Zhikang ZHU ; Zhen HUANG ; Guofeng BAO ; Yuyu SUN ; Lingling WANG ; Ying CUI
Journal of Biomedical Engineering 2011;28(4):774-779
The present research was aimed to explore the biocompatibility of IKVAV self-assembling peptide nanofiber scaffold with olfactory ensheathing cells (OECs) of rats. The OECs were seeded onto the surface of coverslips covered with IKVAV self-assembling peptide nanofiber scaffold hydrogel (2D culture system), and implanted within IKVAV self-assembling peptide nanofiber scaffold hydrogel (3D culture system), respectively. The adhesion, viability of OECs were observed with inverted microscope. Then the characteristics for survival and adhesion of cells by image processing were observed, and statistical analysis on the number of S-100 positive cell, the area of the cell bodies and the perimeter of the cell and MTT method were carried out. It was found that the OECs could survive and migrate in IKVAV self-assembling peptide nanofiber scaffold. The result of the cell MTT exam, of the shape and quantity of cells had no significant difference compared to those of the OECs cultured with poly-L-lysine (PLL). It has been proved that IKVAV self-assembling peptide nanofiber scaffold has good biocompatibility with rat OECs.
Animals
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Animals, Newborn
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Biocompatible Materials
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chemistry
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Cell Proliferation
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Cells, Cultured
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Hydrogel, Polyethylene Glycol Dimethacrylate
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chemistry
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Laminin
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chemistry
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Nanofibers
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chemistry
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Olfactory Bulb
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cytology
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drug effects
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Peptide Fragments
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chemistry
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Rats
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Rats, Sprague-Dawley
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Tissue Engineering
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methods
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Tissue Scaffolds
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chemistry

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