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).

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.

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.

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.

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.

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.

Objective To study the effect of three different modes of non-invasive positive pressure ventilation on cardiac indices of premature infants with respiratory distress syndrome (RDS).Method From January 2014 to October 2015,preterm infants who had RDS received intubation-pulmonary surfactantextubation in the neonatal intensive care unit of the Hospital were randomly assigned (by random number table) to three groups based on the primary mode of ventilation:nasal continuous positive airway pressure (NCPAP),bi-level positive airway pressure (BiPAP),and synchronized bi-level positive airway pressure (SBiPAP).The mean airway pressure (MAP) were about 6 cmH2O in the three groups.The level of plasma B-type natriuretic peptide (BNP),cardiac troponin Ⅰ (cTnI),and correct QT intervals dispersion (QTcd) were monitored before and 42-54 h after non-invasive ventilation.Result There were 173 cases in our study,59 of which in NCPAP group,56 in BiPAP group,and 58 in SBiPAP group.The plasma BNP level at 42-54 h after non-invasive ventilation in the three groups were all higher than that before non-invasive ventilation [NCPAP group:(247.9 ± 137.9) ng/L vs.(182.5 ± 1 10.7) ng/L,P =0.007;BiPAP group:(258.5 ± 131.2) ng/L vs.(182.6 ± 105.0) ng/L,P ＜ 0.001;and SBiPAP group:(260.9 ± 159.7) ng/L vs.(177.5 ± 101.5) ng/L,P =0.002].After 42-54 h non-invasive ventilation,there were no significant changes of plasma cTnI level and QTcd in all the three groups (all P ＞ 0.05).The level of plasma BNP,cTnI,and QTcd among the three groups before and after 42-54 h non-invasive ventilation all showed no significant differences statistically (all P ＞ 0.05).Conclusion Longer duration (42-54 h) of non-invasive positive pressure ventilation (MAP:6 cmH2O) in preterm infants with RDS may lead to increased plasma BNP level,and may affect their cardiac function.However,it may not lead to serious myocardial damage and abnormality of ventricular repolarization.There were no significant differences in cardiac indices of premature infant with RDS among NCPAP,BiPAP,and SBiPAP group with the same MAP.

BACKGROUND:Chitosan biological materials can induce bone marrow mesenchymal stem cells to differentiate toward neurons. As a derivative of chitosan, carboxymethyl chitosan has a series of excelent properties. However, whether carboxymethyl chitosan can induce the neuronal differentiation of bone marrow mesenchymal stem cells remains unclear.OBJECTIVE:To investigate the effect of carboxymethyl chitosan thermosensitive hydrogel on the differentiation of bone marrow mesenchymal stem cells into neurons and the possible mechanism.METHODS:Passage 3 bone marrow mesenchymal stem cells from rats were selected and cultured in carboxymethyl chitosan thermosensitive hydrogel extracts in different concentrations (0, 50, 100, 150, 200, 500 g/L). Control cells were cultured in culture medium with no addition of carboxymethyl chitosan thermosensitive hydrogel extracts. MTT assay was performed to investigate the effects of different concentrations of carboxymethyl chitosan thermosensitive hydrogel extracts on bone marrow mesenchymal stem cell proliferation. Western blot assay was used to explore the effect of 150 g/L carboxymethyl chitosan thermosensitive hydrogel extracts on the expression of neuron-specific enolase, Nestin, Vimentin, NF-M, microtubule associated protein 2, glial fibrillary acidic protein, β3-tubulin, Notch1 and Jag1 protein.RESULTS AND CONCLUSION:MTT assay showed that carboxymethyl chitosan thermosensitive hydrogel promoted the cell proliferation, and the proliferation rate reached the peak at the concentration of 150 g/L. Western blot assay showed that the cells induced by 150 g/L carboxymethyl chitosan thermosensitive hydrogel extract had significant increases in neuron-specific enolase, Nestin, Vimentin, NF-M, microtubule associated protein 2, glial fibrillary acidic protein, and β3-tubulin protein expression, and obvious decreases in Notch1 and Jag1 protein expression in comparison with the control group. These results indicate that the carboxymethyl chitosan thermosensitive hydrogel induces rat bone marrow mesenchymal stem cells to differentiate toward neurons, and suppresses the activity of Notch signal pathway in the process of differentiation.

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.

Objective:To explore the role of cytokines in the pathogenesis of Graves′disease(GD),by detecting the levels of IFN-γ,IL-6,IL-17 and TGF-β1 in GD patients who were newly diagnosed.Methods:A total of 23 patients with new onset GD and 23 gender-and age-matched healthy controls were examined.The levels of serum IFN-γ, IL-6, IL-17 and TGF-β1 were measured by ELISA,FT3,FT4 and TSH levels were determined by ECL IA;TrAb levels were tested by RRA.Results: There were no significant difference among GD and NC group in sex and age match ( t=0.334 8 ,P>0.05;χ2=0.410 7 ,P>0.05 ).The levels of serum IFN-γ,IL-6,IL-17 and TGF-β1 in the GD group were significantly higher than the control group ( P<0.05 ) .Correlation analysis revealed that IFN-γ,IL-6,IL-17 and TGF-β1 were positively correlated with FT3,FT4(r=0.324 6,0.453 2,0.431 0,0.463 8;0.413 2,0.441 5, 0.436 2,0.467 1;P<0.05 ).Conclusion: IFN-γ, IL-6, IL-17 and TGF-β1 are highly expressed in the newly diagnosed GD patients.They play an important role in the pathogenesis of GD ,and provide helpful evaluation indices of immune dysfunction to Graves disease.