BACKGROUND:The emergence of human induced pluripotent stem cel s (iPSCs)-derived dopaminergic neurons solves the problem that the embryonic stem cel (ESC) shows an ethical issue on its source, providing a promising cel source for treatment of Parkinson’s disease.
OBJECTIVE:To summarize the differentiation methods of iPSCs-derived dopaminergic neurons in vitro, the choice of Parkinson’s disease models and the transplantation of iPSCs-derived dopaminergic neurons in the Parkinson’s disease treatment.
METHODS:In order to search relevant articles about the application of iPSCs-derived dopaminergic neurons in the Parkinson’s disease models from PubMed databases (from 1980 to 2015), a computer-based search was performed by the first author, using the key words of“iPSC and Parkinson’s disease, induced pluripotent stem cel s and Parkinson’s disease, ES cel s and Parkinson, PD model, Parkinson and Lewy bodies”in English. Final y 40 articles were chosen for further analysis.
RESULTS AND CONCLUSION:Here, this paper is detailed to show the research status of human iPSCs-derived dopaminergic neurons for treating Parkinson’s disease by reviewing the sources and in vitro differentiation schedules of iPSCs as wel as the choice of Parkinson’s disease models and outcomes of transplantation of iPSCs-derived dopaminergic neurons for Parkinson’s disease treatment. According to the Parkinson’s disease mechanism of the Lewy body, we analyze the generation mechanism of the Lewy body, providing references to avert the presence of Lewy bodies and optimize the outcomes of transplantation. The improvement of differentiation conditions of iPSCs can markedly improve the behavior outcomes, and moreover, we can systematical y evaluate the outcomes of transplantation by iconography and immunohistochemical results.

Objective To investigate the inhibitive effect of mesenchymal stem cells (MSCs) on the immunological rejection in rats after liver transplantation. Methods The recipients and donors were female SD rats and Wistar rats. All rats were randomly divided into 3 groups (28 rats in each group). Rats in group A were infused with normal saline; rats in group B received FK506 (0.25 mg/kg) every 2 days for 2 weeks after liver transplantation; rats in group C were injected with MSCs from male Wistar rats during liver transplantation. The pathological changes, expression of TGF-β1 and IL-10, Y chromosome location, changes of liver function and the survival of the recipients were detected on postoperative day 10. The levels of ALT and AST were analyzed by com-pletely randomised design analysis of variance, and the difference among the 3 groups were analyzed by LSD. Ridit was used to analyze the pathological grading. The survival was analyzed by Log-rank test after the Kaplan-Meier survival curve was drawn. Results The values of ALT and AST were (756±104)U/L and (635±134)U/L in group A, (197±49)U/L and (331±78) U/L in group B, (103±31)U/L and (150±38) U/L in group C, respectively. The difference in the level of ALT and AST among the 3 groups had statistical significance (F = 158, 265, P < 0.05). The liver function of rats in group B and C was better than those in group A (P < 0.01), and the liver function of rats in group C was better than those in group B. The mean values of ridit in group A, B and C were 0.8333, 0.4583 and 0.2083, respectively. The expression rates of TCG-β1 in group A, B and C were 18%±5% , 69%±20% and 85%±24% , with statistical difference among the 3 groups (F=191, P <0.01). There was a significant difference in IL-10 expression among group A (21%±5%), group B (75%±14%) and group C (91%±21%) (F=672, P<0.01). The TCG-β1 and IL-10 had strong positive expression in group B and C, and the expression of TCG-β1 and IL-10 was much stronger in group C than in group B; while the expres-sion of TCG-β1 and IL-10 was weak positive in group A. MSCs cells with Y chromosome were positively stained and were concentrated at the portal area in group C. The 50-day survival rate of rats in group A, B and C were 0, 10% and 90% , respectviely, with significant difference (χ~2=36, P < 0.01). The median survival time of rats in group C was 63 days, which was longer than that in group A and B. Conclusion Simultaneous injection of MSCs from donors during liver transplantation can inhibite the immunological rejection of recipients to the liver graft.

BACKGROUND: Several studies have demonstrated that sphingosine-l-phosphate(S1P)can induce the differentiation of adipose-derived stem cells differentiation into smooth muscle cells.Whether S1P,rather than 5-azacytidine,can be used as an inducer of mesenchymal stem cells differentiation into cardiomyocytes remains unclear.OBJECTIVE: To investigate the possibility that S1P promotes human umbilical cord mesenchymal stem cells(HUMSCs)differentiation into cardiomyocytes in the presence of different culture media.METHODS: HUMSCs were cultured with cardiomyocyte conditional medium(CMCM)and/or SIP media.At 1,5,and 10 days of culture,morphological changes of HUMSCs were observed.After culture for 10 days,the induced cells were confirmed by immunocytochemical analysis and patch clamp in terms of cell phenotype and function.RESULTS AND CONCLUSION: During the induction,some cells gradually enlarged,elongated,connected with adjacent cells,and formed myotube-like structures,and some cells congregated into cell clusters in the CMCM and CMCM+S1P groups.In the CMCM+S1P group,cells exhibited special perpendicular terrace-shaped,intercalated disc-like arrangement.Immunohistochemistry results revealed that some cells strongly express specific antibodies against sarcomeric myosin andα-actinin in the CMCM and CMCM+S1P groups.These findings suggest that HUMSCs can be induced to differentiate into cardiomyocytes.Through the use of patch clamp technique,a rapid ascending,but without plateau phase,action potential,a voltage dependent inward current,and a voltage dependent outward current were recorded in some cells from the CMCM+S1P group.These findings indicate that S1P plays a key role in promoting cardiomyogenic differentiation of HUMSCs and functional integration.

AIM To investigate the tissue distribution of brucine-loaded solid lipid nanoparticles in mice in vivo.METHODS Mice were intravenously injected with suspension of prepared brucine-loaded solid lipid nanoparticles and marked by fluorescein isothiocyanate (FITC).The in vivo tissue distribution of nanoparticles was analyzed by having the brucine contents in various tissues (heart,liver,spleen,lung,kidney and bone) determined by HPLC,after which fluorescence confocal laser endomicroscopy was used for further detection.RESULTS Brucine had its the highest (1.64) relative intake efficiency (Re) in mice liver,and the nanoparticles shared all over one value of targeting efficiencies (Te) in various tissues,manifesting a much stronger selectivity to liver than that of brucine solution.With the extension of time,the FITC-narked nanoparticles displayed a rich extracellular to intracellular distribution indicating a positive correlation.CONCLUSION Brucine's increased distribution in the liver tissue of mice due to its solid lipid nanoparticle form shows obvious for liver targeting.

Objective To evaluate the diagnostic value of magnetic resonance enterography(MRE)and ectopic gastric mucosa imaging(EGMI)in children with lower gastrointestinal hemorrhage.Methods The clinical data including gender,age,amount of bleeding and preoperative minimum hemoglobin(Hb)levels of 54 children with lower gastrointestinal hemorrhage were collected,who received surgical exploration in Department of Pediatric Surgery,Anhui Provincial Children's Hospital between February 2014 and April 2016.Children were divided into lesion group and non-lesion group according to the findings of surgical exploration.Lesion group were defined as children with Meckel's diverticulum(MD)or duplication of the small intestine by surgery and postoperative pathological findings.A total of 36 cases,25 cases of boys,11 cases of girls,aged(2.86±1.59)years old.Non-lesion group were defined as children,who underwent operation with negative result or with lesions but not MD or duplication of the small intestine.A total of 18 cases,14 cases of boys,4 cases of girls,aged(3.87±1.62)years old.MRE and EGMI were performed when the children stopped bleeding,before the inspection,should fasting for 4-6 h.SPSS 13.0 software was used for statistical processing.The evaluation of EGMI,MRE and the both in diagnosing MD or duplication of the small intestine were conducted by receiver operating characteristic curve(ROC).According to the principles of biggest gain best diagnostic value by Youden index,and the degree of sensitivity and specificity was calculated at this time,P<0.05 for the difference was statistically significant.Results There was no significant differences statistically in gender between 2 groups(x2=0.415,P>0.05).There were statistically significant differences in age,amount of bleeding and preoperative minimum hemoglobin levels(t=2.179,2.027,2.222,all P<0.05).There were statistically significant differences in classification comparison by EGMI and MRE between 2 groups(x2=15.226,29.121,all P<0.01).The optimal cut-off value of EGMI and MRE in the diagnosis of enteric malformation was more than level 3,and the suspected positive and being positive value was assigned as positive results.According to the cut-off value above,EGMI,MRE and EGMI plus MRE in series and in parallel in the diagnosis of enteric malformation,the areas under curves(AUC)were 0.809,0.917,0.750 and 0.847,respectively.The sensitivity was 61.1％,75.0％,55.6％and 80.6％,respectively.The specificity was 90.4％,94.4％,94.4％and 88.9％,respectively.The Youden's indexes were 0.515,0.694,0.500 and 0.695,respectively.The optimal cut-off value of age and preoperative minimum hemoglobin levels in the diagnosis of enteric malformation were 2.92 years and 80 g/L,respectively.The AUC was 0.761 and 0.672.The Youden's indexes were 0.515 and 0.333.There was no significant differences statistically in AUC compared with age,MRE and EGMI(all P<0.05).Conclusions The high diagnostic value in children with lower gastrointestinal hemorrhage is found by using MRE and EGMI.Then,MRE as a separate diagnosis method is also worthy of clinical application.

ObjectiveTo study the therapeutic effects of cerebellar fastigial nucleus electrical stimulation (FNS) on motor and depression symptoms and monoamine neurotransmitters in the spinal cord fluid of patients with Parkinson's disease (PD).Methods65 patients with idiopathic Parkinson's disease following depression were divided into stimulation group (FNS+Madopar, n=35) and control group (Madopar, n=30). The stimulation group took Modopar, and treated with FNS, 30 miniutes once a day for 30 days. The control group took Modopar only. Madopar dose has no change during the treatment. The patients were evaluated by Webster Parkinson's Disease Evaluation Form, and Hamilton Depression Scale (HAMD) before and after FNS treatment. The loading of monoamine neurotransmitters was measured by high performance liquid chromatography-electrochemical process.ResultsAfter the treatment, the stimulation group improved in clinical feature and depression, scored significantly lower on Webster and HAMD than the control group(P<0.05); the loading of 5-hydroxytryptamine(5-HT) in spinal cord fluid increased; however noradrenalin and dopamine had no different. But there was no significant change in the symptoms and the loading of monoamine neurotransmitters in the control group.ConclusionFNS is efficient to relieve the motor and depression symptoms of PD, which possible mechamism might be central neuroprotection and the release of 5-HT by FNS induction.

Objective To investigate the effect of CXCL12 on the secretion of CXCL8 from colon cancer cells and the mechanism of co-regulation of proliferation and metastasis of colon cancer.Methods The expression levels of CXCL8 and CXCl12 in 5 human colon cancer cell lines (DLD-1,HT29,WiDr,CaCo-2,Colo320),fibroblasts,and human umbilical vein endothelial cells (HUVEC) were studied by Western blotting,respectively.ELISA,proliferation and invasion assay were used to explore the role of CXCL12 and CXCL8 for metastatic process of colon cancer and interaction between colon cancer cell and stromal cell in the microenvironment,respectively.Results The expression of CXCL8 was detected in all colon cancer cell lines,fibroblasts and HUVEC,while CXCL12 was expressed only in DLD-1 cell and fibroblast.The secretion level of CXCL8 in CaCo-2,WiDr,HT-29 and HUVEC (2.54-fold vs.control,2.07-fold vs.control,1.87-fold vs.control,2.79-fold vs.control) was enhanced by CXCL12 that derived from fibroblasts(P ＜ 0.01).CXCL8 could significantly promote the proliferation,migration of HUVEC (P ＜0.01).CXCL8 and CXCL12 enhanced proliferation of HUVEC (P ＜ 0.01),invasion of HUVEC and HT-29 (P ＜ 0.01) in a concentration-dependent manner.Conclusion Fibroblasts derived CXCL12 enhanced the CXCL8 secretion in colon cancer cells,and CXCL8 and CXCL12 can promote the proliferation and invasion of colon cancer cells.

Objective To investigate the expressions of PGE2 and COX-2 between colorectal cancer tissue and normal colorectal mucosa tissue,and its relation to clinical pathology and significance.Methods 115 colon cancerous tissues and 69 normal colon tissues were collected in our hospital from Jan 2010 to Sept 2011.Immunohistochemistry was used to detect the PGE2 and COX-2 expression in both of the colorectal cancer and normal tissues.Results Positive expressions of PGE2 and COX-2 were 87.8％ (101/115) and 80.9％ (93/115) in the colorectal cancer tissue,and 8.7％ (6/69),21.7％ (15/69) in normal colorectal mucosa tissue respectively (x2 =110.96,62.194,all P ＜ 0.05).Expressions of PGE2 and COX-2 were closely associated with,tumor invasion,differentiation,lymph node metastasis and TNM stage (P ＜ 0.05).The Spearman rank correlation analysis indicated that the PGE2 and COX-2 expressions in tissues were closely correlated (r =0.987,P ＜ 0.05).Survival rate of the patients in both negative expressions of PGE2 and COX-2 (63.6％) were higher than that of both positive expressions (37.8％,P ＜ 0.05).Conclusion High PGE2 and COX-2 expressions in colorectal cancer tissues predicts poor patients' survival.

Objective To evaluate the efficacy of nasotracheal intubation for airway management in neonates with Pierre Robin sequence undergoing surgery with general anesthesia. Methods Sixty full-term neonates of both sexes with Pierre Robin Sequence, aged 2-28 days, weighing 2. 4-3. 8 kg, scheduled for elective mandibular distraction osteogenesis, were divided into 2 groups ( n=30 each) using a random num-ber table method: nasotracheal intubation group (group N) and orotracheal intubation group (group O). Combined intravenous-inhalational anesthesia was used during surgery. The success rate of intubation, intu-bation time, heart rate, mean arterial pressure and SpO2 during intubation, and occurrence of complica-tions during intubation were recorded, and the time of extubation and occurrence of complications after extu-bation were also recorded. Results Compared with group O, the intubation time was significantly short-ened, the first-time intubation success rate was increased, the heart rate and mean arterial pressure were decreased at 2 min after intubation, the lowest SpO2 was increased during intubation, and the incidence of pharyngeal soft tissue injury during intubation and hoarseness after extubation was decreased in group N ( P<0. 05) . Conclusion Nasotracheal intubation can be used for airway management in neonates with Pierre Robin sequence undergoing surgery under general anesthesia, and the efficacy is superior to that of orotra-cheal intubation.