1.Composite pheochromocytoma-ganglioneuroma: a clinicopathologic and literature review
Likun GAO ; Honglin YAN ; Jingping YUAN
Chinese Journal of Clinical and Experimental Pathology 2017;33(3):258-262
Purpose To explore the clinicopathological features,immunophenotype,differential diagnosis and prognosis of the composite pheochromocytoma (CP)-ganglioneuroma.Methods 3 cases of CP-ganglioneuroma were stained by immunohistochemical SP method,and the related literatures were reviewed.Results 3 cases of CP-ganglioneuroma were one male and 2 females,the age were 37-64.Case 3 were of primary mediastinal.Microscopically,the tumor tissues were composed of two components:one type of tumor cells were arranged in nests with a predominant Zellballen pattern,round or oval nuclei,fine granular cytoplasm and rare mitotic,another part of the neoplasm showed scattered and aggregated distributed ganglion cells in the background of neurofibromatosis which aligned bundles and interwoven,the edge of the tumor was still residual adrenal tissue.Immunohistochemically,components of pheochromocytoma were positive for CD56,CgA,Syn,vimentin and negative for SMA,Melan-A,α-inhibin NF with low Ki-67 proliferation index.S-100 was positive in supporting cells,ganglioneuroma components were positive for NF,S-100 with low Ki-67 proliferation index.CgA and Syn were weakly positive or negative in the ganglion cells.Conclusion CP is a relatively rare tumor,which can not be distinguished from pheochromocytoma in clinical and radiological diagnosis.The corresponding clinical treatment and follow-up management should be taken according to the different ingredients (benign or malignant).
2.Study of copy number variations in children with unexplained mental retardation/brain development delay
Jing GAO ; Yao YANG ; Honglin WU ; Xiyu HE
Chinese Journal of Applied Clinical Pediatrics 2016;31(20):1550-1555
Objective By using array-based single nucleotide polymorphisms comparative genomic hybridization (SNP-aCGH) to detect and fine mapping copy number variations (CNVs) in children with unexplained mental retardation/brain development delay(MR/BD),then the CNVs were analyzed to determine diagnosis and offer genetic counseling,finally to discuss the application of SNP-aCGH in genetic diagnosis of MR/BD with unknown causes.Methods Ninety-two children with unexplained MR/BD were recruited.SNP-aCGH was used to get CNVs from the whole genome-wide,and the correlation of CNVs and phenotype was analyzed to definit disease genes or pathogenic fragment.Statistics was performed to analyze the common phenotype between positive cases (case with CNVs) and negative cases.Results (1) The CNVs were detected in 10 cases with a detection rate of 10.86%,from which 8 cases showed subtelomeric aberration,5 cases without subtelomeric aberration,and the rate was 8.70%,5.40%,respectively.The CNVs related to MR/BD involved 10 different subtelomeric regions (9p,21q,3p,2p,15q,4p,12p,22q,16p,17p),and 7 different regions without subtelomeric (1p,4q,2p,14q,15q,12q,22q).The deletions involved 11 zones (size:1.05-8.80 Mb),and duplications referred to 8 zones (size:1.33-31.25 Mb).(2) One case was diagnosed as 9p duplication syndrome,for candidate genes:DOCK8,VLDLR.A case was detected with a gene fracture (CRBN).One case was diagnosed as Coffin-Sirrs syndrome combined with a deletion of 15q26.3-qter,for candidate genes:SOX11 and LINS1,respectively.One case referred to 12p13.3 deletion syndrome,for candidate genes:ELKS,ERC1.One case referred to 22q13.2-qter deletion,for candidate genes:SHANK3.Two cases were diagnosed as ATR-16 syndrome with 17p13.3 deletion syndrome,their candidate genes:HBA1,HBA2,SOX8 for the former,YWHAE,LIS1 for the latter.(3)There were statistically significant differences in comparison of positive cases to the negative ones for growth delay,internal organs deformity,low birth weight infant(LBW) and premature infant (all P <0.05).Conclusions (1) Besides MR/BD in different degrees in all the positive cases,they also showed growth delay,a portion of them with internal organs deformity,low birth weight infant and premature infant.(2) Subtelomeric aberrations are related to MR/BD,while the submicroscopic rearrangement in regions without subtelomeric is suspiciously pathogenic,and need to be further studied.(3) SNP-aCGH can fine mapping the region of CNVs by high resolution from the whole genome-wide,which does contribute to limit the zones for finding pathogenic region and candidate genes,as well as to offer a technology platform for investigating about the correlation of phenotype and genes or CNVs.
3.Change of soluble P-selectin and soluble E-selectin levels in patients with type 2 diabetes mellitus with or without coronary heart disease
Yanqiu LIU ; Meihua GAO ; Honglin LI ; Changyin XIE ; Haifei ZHANG
Chinese Journal of Immunology 2015;(9):1245-1249
Objective:To explore the vailation of serum sP-selectin,sE-selectin,levels in the patients of pre-diabetic,simple type 2 diabetes mellitus (T2DM) and T2DM with coronary heartdisease(CAD).To investigate the possible mechanism that sP-selectin, sE-selectin accelerate type 2 diabetes mellitus.Methods: Level of serum sP-selectin, sE-selectin was assayed by ELISA in type 2 diabetes with or without coronary heart disease (32 and 34 cases respectively),pre-diabetic (32 cases) and control group(32 cases). Meanwhile BMI,BP,FBS,FINS,TG,CHO,HDL-C,LDL-C,HbA1C were determined in all cases as well as in control group.Results:The serum levels of sP-selectin and sE-selectin in pre-diabetic,type 2 diabetes mellitus with or without coronary heart disease groups were significantly higher than the control group ( P<0.01 ).There was significant positive correlation between serum levels of sP-selectin,sE-selectin and these items including FBG ,FINS,TG,HbA1C,HOMA-IR(P<0.01);but sE-selectin was negatively correlated with HDL-C (P<0.05).Conclusion:sP-selectin,sE-selectin,are risk factors in the initiation and progression of pre-diabetic,type 2 diabetes with or without coronary heart disease;sP-selectin and sE-selectin possibly accelerate type 2 diabetes by inducing insulin resist-ance.
4.Diagnostic value of array-based single nucleotide polymorphisms comparative genomic hybridization in An-gelman syndrome
Jing GAO ; Xiyu HE ; Yao YANG ; Honglin WU
Chinese Journal of Applied Clinical Pediatrics 2015;(18):1401-1404
Objective To analyze the genotype-phenotype correlations of Angelman syndrome ( AS ) , and to discuss the advantage of applying array-based single nucleotide polymorphisms comparative genomic hybridization ( SNP aCGH) in diagnosis of AS. Methods Examination of electroencephalogram( EEG) and intelligence quotient( IQ) evaluation were done for 11 cases diagnosed as AS clinically. Gesell scares were chosen as the evaluation criterion of IQ. The screening techniques was methylation polymerase chain reaction( MS-PCR) ,then SNP aCGH was used to make genetic diagnosis. Results (1)Eleven cases of AS were confirmed:1 case had UPD(uniparental disomy),10 cases were type of deletion, from which 6 cases were deletion (Ⅱ) , 4 cases were deletion (Ⅰ) . ( 2 ) The copy number variations were detected in the region of 15q11-q13,which contained genes like MKRN3,MAGEL2,NDN,SNRPN, SNURF,GABRB3,GABRA5,GABRG3,UBE3A,OCA2,ATP10A. To search online Mendelian inheritance in man,genes above were correlated with AS manifestation. (3)All cases of deletion were 3-5 standard deviation(SD) in weight and height to normal children at the same age and with the same sex,while UPD was below 1. 5 SD. Gesell scares showed that the deletion(Ⅰ) was the most serious in mental retardation,deletion(Ⅱ) was moderate,and the UPD was mild. Eight cases were hypopigmentation,and one was the UPD. EEG revealed that 1 case of deletion(Ⅰ) and the UPD were spike occasionally,another one deletion(Ⅰ) was limit EEG. The rest cases displayed slow and spike waves paroxysmal-ly,with amplitude of medium or high,2. 5-3. 0 Hz. Conclusions Not only can SNP aCGH make a diagnosis of AS but discriminate the types of genetic pathology. Since different type contributes to a diverse of clinical features and the rate of recurrence is also different,it is significant for family genetic consultation. Moreover,the technology is advantageous for the study on the pathogenesis and gene function.
5.Application of multimodal imaging in stem cell research
Honglin GAO ; Naling SONG ; Zhongli SUN ; Cuihong YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2015;35(5):407-409
In recent years,stem cell research has been developing quickly in biological science.As the key of regenerative medicine,stem cell therapy becomes another innovative treatment following drug therapy and surgery.In vivo stem cell tracking,including optical imaging,radionuclide imaging and MRI,can trace the viability,distribution and function of engrafted cells.Multimodal imaging integrates two or more types of imaging techniques to obtain the combined advantages of each technology,and therefore is able to accurately and effectively trace stem cell in vivo,hopefully promoting its clinical transformation.This paper reviews the application of multimodal imaging in stem cell research.
6.Analyzing Opening System of Experiment Teaching of Medical Function
Zhiping GAO ; Bi HU ; Boyong LI ; Honglin HUANG ; Duanfang LIAO
Chinese Journal of Medical Education Research 2003;0(04):-
To deepen the teaching reform on comprehensive medical function experiment in our school,the mode of opening system of experiment teaching of medical function is proposed.The definition and characteristics of the opening system is discussed in this paper,and its theoretical foundation,guideline,goal location,effect and pending problems are also explored preliminarily.
7.Expression of Th17 cells and related cytokines in peripheral blood of patients with Graves′disease
Honglin LI ; Zhikui DENG ; Yunhui ZHENG ; Yanqiu LIU ; Xiaoning LIU ; Shijun YANG ; Weiping LU ; Meihua GAO
Chinese Journal of Immunology 2016;32(4):563-566
Objective:To explore the proportions of Th17 cells in the peripheral blood and levels of IL-17,IL-23 in the serum of patients with Graves′disease ( GD ) and their clinical significance.Methods: We studied 29 patients with GD ( GD group ) , and reevaluated the GD group after therapy ( euthyroid GD group ).29 gender-and age-matched volunteers were selected as the normal control ( NC group).The proportions of Th17 cells were investigated by flow cytometry.The levels of IL-23,IL-17 in the serums were measured by ELISA.The levels of FT3,FT4,TSH were determined by ECLIA and the levels of TrAb were tested by RRA.Results:There were no significant difference among 3 study groups in sex and age match ( F=0.0075 , P>0.05;χ2=0.4213 , P>0.05 ).The proportions of Th17 cells and the levels of IL-17 , IL-23 were increased in the GD and euthyroid GD patients compared with the control group (respectively,P<0.05).The proportions of Th17 cells and the concentrations of IL-23 in euthyroid GD group were significantly lower than those of GD group ( respectively , P<0.05 ) , but there were no significance in the concentrations of IL-17 between euthyroid GD group and GD group(P>0.05).Correlation analysis revealed that the proportions of Th17 cells ,and the levels of IL-17,IL-23 were positively correlated with the levels of FT3,FT4,TrAb(r=0.588 2,0.337 2,0.371 0;0.549 6,0.287 5,0.342 7;0.361 0,0.420 8, 0.330 8;P<0.05 ,for all parameters ) ,and were negatively correlated with the levels of TSH ( r=-0.319 7 ,-0.472 8 ,-0.428 2;P<0.05,for all parameters).Conclusion:Th17 cells and their related cytokines IL-17,IL-23 are highly expressed in the serum of patients with GD.Th17 cells and their relative cytokines have certain relevance with 4 thyroid function parameters of the patients with GD , which can be used as biological markers for GD.
8.Changes of three cardiac markers at pre - and post -treatment in preterm infants with patent ductus arteriosus
Bo YANG ; Niannian TONG ; Xiangyu GAO ; Xiuli WANG ; Xiangjun CUI ; Honglin LEI ; Yi REN ; Mingyan HEI
Chinese Journal of Applied Clinical Pediatrics 2016;(3):212-216
Objective To investigate the changes of cardiac function at pre -and post -treatment in preterm infants with patent ductus arteriosus (PDA)in order to guide drug treatment.Methods Totally 84 preterm infants with PDA admitted to Neonatal Intensive Care Unit of Xuzhou Hospital Affiliated to Medical College of Southeast University from July 201 2 to June 201 4 were divided into 4 groups according to treatment drug:Ibuprofen group (27 cases),Indo-methacin group (24 cases),control group (1 1 cases),and Paracetamol group (22 cases).Patients were also divided into symptomatic PDA group (38 cases)and asymptomatic PDA group (46 cases)according to severity;PDA closed group (69 cases)and PDA unclosed group (1 5 cases)according to sequel.The level of plasma brain natriuretic pep-tide (BNP),cardiac troponin I (cTnI),correct QT intervals dispersion (QTcd)were monitored pre -and post -treat-ment.Data were analyzed by using SPSS 1 9.0 software.Results Three cardiac markers at post -treatment were of no significant difference among 4 treatment drugs.The changes of the cTnI and QTcd at pre -and post -treatment were of no significance.The level of BNP in symptomatic PDA group was significantly higher than that in asymptomatic PDA group at pre -treatment [(378 ±94)ng/L vs (1 47 ±75)ng/L,t =2.584,P =0.01 4].In the symptomatic PDA group,the level of BNP at post -treatment [(1 82 ±81 )ng/L]was significantly decreased than that at per -treatment (t =2.741 ,P =0.009).In the asymptomatic PDA group,there was no significant difference between the pre - and post -treatment [(1 21 ±61 )ng/L]in the level of BNP (t =1 .254,P =0.207).There was no significant difference in the level of BNP at per -treatment between PDA closed group and PDA unclosed group [(274 ±91 )ng/L vs (289 ± 87)ng/L,t =-0.874,P =0.391 ].In PDA closed group,the level of BNP at post -treatment [(1 21 ±74)ng/L] was significantly decreased compared with that at per -treatment (t =3.580,P =0.000).In PDA unclosed group, there was no significant difference between the pre - and post -treatment [(245 ±74)ng/L]in the level of BNP (t =0.854,P =0.392).Conclusion Early medication intervention for symptomatic PDA of preterm infants is benefi-cial for the closure of PDA and for attenuating negative effects on cardiac function of PDA.
9.Synthesis of acid-sensitive doxorubicin prodrug nanoparticle and its application in brain glioma treatment
Jinjian LIU ; Yumin ZHANG ; Cuihong YANG ; Liping CHU ; Fan HUANG ; Honglin GAO ; Jianfeng LIU
Tianjin Medical Journal 2016;44(1):33-37
Objective To synthesize a new kind of acid-sensitive doxorubicin prodrug nanoparticles and to evaluate its anti-brain glioma effect and efficiency through blood-brain barrier (BBB). Methods The prodrug acid-sensitive poly-ethylene glycol (PEG)-doxorubicin (PEG-DOX) copolymer was synthesized by Schiff base reaction, and PEG-DOX pro-drug nanoparticles (PEG-DOX NPs) were prepared by self-assembling. The character of PEG-DOX copolymer was detected by dynamic light scattering (DLS) instrument and 1H NMR. The morphology of PEG-DOX NPs was observed by transmission electron microscopy (TEM). The character of drug release was detected by UV mothed. The cellular uptake efficiency of glio-ma cells to PEG-DOX NPs was observed by inverted fluorescence microscope. The anti-brain glioma effects of PEG-DOX NPs and Free DOX were studied by MTT mothed. PS80-PEG-DOX NPs were gained by the modification of PEG-DOX NPs with Tween 80. Nine BALB/c mice were separated into Free DOX, PEG-DOX NPs and PS80-PEG-DOX NPs groups by ran-dom drawing lots. The mean fluorescence intensity of brain and main organs were observed by in vivo imaging system. Re-sults The copolymer of PEG-DOX can self-assemble into nanoparticles with the diameter of 100 nm. PEG-DOX NPs can quickly release DOX in acid environment. Although PEG-DOX NPs had slow cancer cell uptake than Free DOX, it had lon-ger accumulation. MTT results showed that PEG-DOX NPs had concentration dependent anti-brain glioma effect. Indepen-dent samples t-test indicated that the efficiency through BBB was significantly higher in PS80-PEG-DOX NPs group than that of Free DOX group and PEG-DOX NPs group. Conclusion PEG-DOX NPs show well anti-brain glioma effect in vi-tro, and can across BBB with high efficiency after modification, which make it possible for a potential therapeutic prodrug for brain glioma.
10.Synthesis of poly asparagine derivatives and its cytotoxicity study
Cuihong YANG ; Jinghua HAN ; Jinjian LIU ; Yumin ZHANG ; Honglin GAO ; Wenhui DONG ; Yanming WANG
Tianjin Medical Journal 2015;(6):582-586
Objective To synthesize poly asparagine derivatives and to evaluate its safety at the cellular level, which provide research platform for its potential application as drug carrier. Methods Polysuccinimide was synthesized by ther?mal polymerization of L-polyaspartic acid, and the target product of PSI-Phe-EA was obtained by the ring-opening reaction of polysuccinimide using L-phenylalanine methyl ester hydrochloride and ethanol amine. The structure of PSI-Phe-EA were characterized by 1H NMR. The rate of ring-opening of PSI was calculated by internal standard method of 1H NMR. The change of hydrophilicity was studied by the comparison of solubility. The cytotoxicity and morphology modification by PSI-Phe-EA at designate concentrations was investigated by MTT method and inverted microscopy respectively. The effects on cell cycles were analyzed by flow cytometry after propidium iodide (PI) staining. Results 1H NMR results confirmed the structure of PSI-Phe-EA and the ring-openning rate of PSI was 40%. The hydrophilicity of PSI-Phe-EA was greatly in?creased upon ring opening using ethanol amine. MTT test showed that the cell survival rates of NIH 3T3 and HepG2 cells were higher than 80%under the examined concentration (<100 mg/L). Inverted microscopy showed that 50 mg/L of PSI-Phe-EA treatment had no adverse effects on cell morphology. Cell cycle analysis indicated that PSI-Phe-EA treatment had no in?fluence on cell cycles of NIH 3T3 and HepG2 cell lines. Conclusion PSI-Phe-EA showed high hydrophilicity without sig?nificant effects on the cells survival, cells morphology and cell cycles. It is a kind of safe polymer material.