Neural stem cells in brains have capacities of proliferation and differentiation, which is very critical to rebuild the cerebral cortex functions. Therefore, it is of great importance to find key targets and network pathways that regulate the proliferation of neural stem cells, which is also a pressing problem in the medical circle. With the Notch pathway as the core of the network, this paper summarized the advance of the bimolecular network system composed of Wnt, Shh, EGFR, cytokines and Notch signal, and analyzed such key nodes as Notch receptor, CBF1, NICD, Hesl, which may become potential targets of new-type drugs in the future. With the multi-component, multi-target, multi-lever characteristics, traditional Chinese medicines have many common grounds with the network pharmacology. The active component groups or active ingredients in traditional Chinese medicines are one of the material bases for showing their network pharmacological effect, which is worth exploring. This paper aims to provide a new strategy for the treatment of neurodegenerative disease and nerve injury with traditional Chinese medicines.
Animals ; Cell Proliferation ; Humans ; Neural Stem Cells ; cytology ; metabolism ; Signal Transduction ; Systems Biology

Objectives To investigate the relationship between single nucleotide polymorphism (SNP)H558R in SCN5A gene and chronic Keshan disease (KSD) complicated with hypertension,and the relationship between H558R and occurrence of arrythmia in chronic KSD complicated with hypertension.MethodsThirty nine patients with chronic KSD complicated with hypertension and 63 geographical region matched hypertension control subjects were recruited in our study in Fuyu county,Qiqihaer city,Heilongjiang province between 2006 and 2010.H558R polymorphism in case and control groups was genotyped using the polymerase chain reaction single-strand conformation polymorphism(PCR-SSCP) and sequenced,and electrocardiography(ECG) characteristics were examined in the two groups.Case-control study analytical methods were applied to analyze the relationship between H558R and chronic KSD complicated with hypertension,and the relationship between H558R and occurrence of arrythmia in chronic KSD patients complicated with hypertension.Results Subjects of genotype 558 TC in the case group had a decreased risk of chronic KSD complicated with hypertension with odds ratio of 0.288[95％ confidence interval (CI):0.104 - 0.794],and subjects of genotype TC in chronic KSD complicated hypertension patients had a decreased risk of QRS prolongation with odds ratio of 0.061 (95％CI:0.006 - 0.612).Conclusions Polymorphism H558R in SCN5A gene may be a predisposition factor of chronic KSD complicated with hypertension and occurrence of arrythmia in chronic KSD complicated with hypertension.

Objective To investigate the distribution status of coal-burning fluorosis (endemic fluorosis) areas in Luoyang and to provide scientifc evidence for making strategies in prevention and control. Methods In 2006, a household per village was chosen to carry the general survey so as of disease condition, living habits and housing structure among 941 coal-burning pollution fluorine sickness natural villages in Yanshi, Mengjin, Xin'an, Luanchuan counties and Geely area which were under the jurisdiction of Luoyang. In the general survey, the sampled village having a population of more than 500 person was considered as a major survey village, and water fluoride, 8 - 12 year-old child fluorine spot on tooth and the urinary fluoride were surveyed. Water fluoride and the child urinary fluoride determination used the fluoride ion selective electrode method, and the children's dental fluorosis used Dean method. Results The endemic fluorosis of Luoyang existed 742 in endemic fluomsis villages, compared with history, a decrease of 199 in number. Ninety-six point seven per cent( 142 543/147 419) of the households were consuming smoke-free coal. Households using intact kitchens accounted for 93.6%( 137 919/147 419). Of which 63.0%(86 889/137 919) of kitchens were mixed up with bedrooms. Total 125 060 people were using coal- fired furnace for heating, of which 87.8%(109 802/125 060) had smoke-free facilities, 12.2%(15 258/125 060) had none. Among 52 endemic villages with population of more than 500 people surveyed, a total of 183 water samples were collected, 2 had water fluoride exceeding 1.0 rag/L, the highest water fluoride being 1.04 rag/L, averaging 0.39 mg/L Sixteen villages had a prevalence rate of dental fluorosis for children less than 30.00%, accounting for 30.8% (16/52), 36 endemic villages the prevalence of dental fluorosis detection rate of more than 30.00%, accounting for 69.2%(36/52). Twenty-thrce villages had a dental fluorosis index greater than 0.6, severe dental fluorosis was not found. Real-time measurement of 1408 urine samples of children aged 8 - 12 showed that urine fluoride highest value 6.88 nag/L, the minimum value of 0.10 mg/L, geometric mean 1.10 mg/L. The prevalence rate of dental fluorosis for children was 36.06%. Conclusions In Luoyang city, numbers of coal-burning endemic fluorosis villages are less than before, children's dental fluorosis has significantly declined, however some people still use kitchens connecting with bedrooms and lack smoke-free facilities, they need to be educated to change lifestyle and improve furnace to reduce soot fluoride pollution.

Objective To evaluate the curative value of the tauroursodeoxycholic acid (TUDCA) and Danning table (DN) in the prevention of bile duct stones recurrence after ERCP. Methods 210 patients with Choledocholithiasisby ERCP were randomly divided into 3 groups. The patients in the control group were not given any medicine. The patients in the TUDCA group took TUDCA every night. The patients in the DN group took Danning tablets of three times a day. The course of medication and followed up for the patients was 24 months after the operation. All the patients would be examined regularly by Biliary color doppler ultrasound and MRCP. The recurrence rates of Choledocholithiasis, cholesterol saturation index and serum lipid were recorded and compared statistically between the three groups. Results In total, 190 patients completed the treatment and follow-up according to the experimental design. The recurrence rates of the control, TUDCA and DN group were 17.46%(11/63), 6.34% (4/63) and 10.94% (7/64). The recurrence rates in the TUDCA and DN group were significantly lower than those the control group (P < 0.05).The recurrence rate in the TUDCA group was significantly lower than that in the DN group; On the tenth days after the operation, the CSI in the TUDCA were significantly lower than those the control group and the DN group (P < 0.05). There was no statistically significant difference between the DN group and the control group (P > 0.05); To the patients without recurrence, the level of TC, LDL in the TUDCA group were significantly lower than those the control group and and the DN group (P < 0.05). The level of HDL in the TUDCA group were significantly higher than those the control group and and the DN group (P < 0.05). There was no statistically significant difference on the level of HDL between the DN groupand the control group (P > 0.05). Conclusion The application of TUDCA and DN for patients with Choledocholithiasis after ERCP can effectively reduce the recurrence rates, the curative effect of TUDCA more than DN.

Objective To understand pathogenic microorganism contamination status of medical waste sharps containers with different use time, explore the reasonable duration of service time of sharps containers, provide reference for the management of medical waste.Methods Twelve 2 L sharps containers on treatment trolleys in a tertiary first-class infectious disease specialty hospital were randomly selected, viral loads of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) as well as bacterial colonies on inner and outer surfaces of sharps containers at different time points were detected, three unused sharps containers were taken as control at the same time.Results Sixty eluent specimens of outer surface and contents of sharps containers in trial group and control group were collected respectively at four time points (48 h, 72 h, 5 d, 7 d), no HIV and HCV were detected, and no HBV was detected in specimens of outer surface of sharps containers, HBV was detected in the eluent of contents in one sharps container 72 hours after the use, concentration of HBV was 2.20 E+01 IU/mL. Changes in bacteria in the eluent of used sharps containers: 100％ of the eluent of contents in sharps containers grew bacteria on the 5 th day after use, bacterial load of the eluent of contents in sharps containers on the 7 th day after use was incalculable. Bacterial load on the outer surface of sharps containers ranged from 1 to 9 CFU/cm2. No significant changes were observed in the inner and outer surfaces of all sharps containers, and no discomfort odor emerged.Conclusion With the storage time prolonged to 7 days, bacterial colonies on the outer surface of sharps containers didn't increase significantly, HIV, HBV and HCV were not detected. It is suggested that service time of sharps containers with small production of contents should not be set compulsorily at 48 hours (even if the contents in sharps container is less than 3/4 of storage capacity after 48 hours of use).

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests

OBJECTIVETo study the methylation status of p73 gene promoter in patients with myelodysplastic syndrome (MDS) and explore its significance with clinical prognosis.

METHODSMethylation of p73 promoter was detected in bone marrow cells from 135 MDS patients and 13 healthy controls by methylation-specific PCR (MSP). The results of MSP were confirmed by bisulfite sequencing. The expression of p73 mRNA was detected by real-time quantitative PCR. Primary bone marrow cells from MDS patients were treated with decitabine, the changes of p73 methylation status and p73 mRNA expression were measured. The role of p73 methylation in the prognosis of MDS and the correlated clinical data were explored.

RESULTSp73 hypermethylation was present in 37.04% of MDS cases and patients with high risk MDS (RAEB-1 and RAEB-2) exhibited a significantly higher frequency of p73 methylation than that of low risk MDS (58.8% vs 29.7%, P = 0.002). The expression of p73 mRNA in the methylated group was decreased compared to that of the unmethylated group (P = 0.032). Decitabine treatment decreased the level of p73 methylation and increased the level of p73 transcripts. Patients with p73 methylation progressed rapidly to AML (P < 0.001) and had shorter survival (P = 0.002) than those who did not have p73 methylation. In the multivariate Cox regression model, BM blast and p73 methylation status emerged as independent prognostic factor for overall survival and leukemia free survival.

CONCLUSIONp73 gene methylation is common in patients with MDS and may indicate poor prognosis. p73 may be a therapeutic target in MDS.

Aged ; Case-Control Studies ; DNA Methylation ; DNA-Binding Proteins ; genetics ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; Nuclear Proteins ; genetics ; Prognosis ; Promoter Regions, Genetic ; Tumor Protein p73 ; Tumor Suppressor Proteins ; genetics

OBJECTIVETo examine the changes in the expression of pro-inflammatory and anti-inflammatory cytokines in the peripheral blood mononuclear cells (PBMCs) and elucidate the inflammatory status of apparently healthy subjects.

METHODSPeripheral blood samples (5 ml) were collected after fasting for more than 8 h from 14 healthy control subjects and 14 apparently healthy subjects with elevated serum high-sensitivity CRP (hsCRP) level (≥ 2.0 mg/L). PBMCs were separated by Ficoll density gradient centrifugation and the total RNA was extracted for real-time quantitative PCR analysis of the inflammatory cytokines, and plasma was separated for ELISA analysis of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expressions.

RESULTSThe gene expressions of TNF-α and MCPIP were significantly increased in PBMCs of apparently healthy subjects, while IL-6 and MCP-1 only showed slight elevations; IL-10 expression in PBMCs decreased significantly in apparently healthy subjects as compared to that in the control group. The results of ELISA showed significantly elevated TNF-α level without significant changes of plasma IL-6 level in apparently healthy subjects.

CONCLUSIONIn apparently healthy subjects with normal lipid levels, chronic low-grade inflammation has occurred shown by elevated expressions of the pro-inflammatory cytokines and lowered expressions of the anti-inflammatory cytokines.

Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Healthy Volunteers ; Humans ; Inflammation ; immunology ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Leukocytes, Mononuclear ; immunology ; Tumor Necrosis Factor-alpha ; blood

This study was purposed to explore the expression of p57kip2 in the bone marrow of patients with de novo myelodysplastic syndrome (MDS) and its role in MDS pathogenesis, as well as the relationship between the expression of p57kip2 and SDF-1/CXCR4 signal. The expression of p57kip2 and CXCR4 in 67 de novo MDS patients was measured by real-time quantitative PCR. The percentage of CD34(+) cells in the bone marrow from MDS patients was measured by flow cytometry. 18 healthy volunteers were recruited for control. The effect of SDF-1 on p57kip2 expression in bone marrow mononuclear cell (BMMNC) from MDS or normal controls was investigated in vitro, and difference between them was compared. The results showed that low-risk MDS and high-risk MDS displayed a significant reduction of p57kip2 mRNA expression in BMMNC compared with that in control group (P < 0.001) and there was a negative correlation between p57kip2 expression and percentage of CD34(+) (r = -0.458, P < 0.001); the patients with abnormal karyotype showed lower expression of p57kip2 gene, compared to patients with normal karyotype (P = 0.045). Although the expression of CXCR4 had no difference between MDS patients and normal controls, a positive correlation between p57kip2 and CXCR4 in MDS patients was still found (r = 0.609, P < 0.001). Moreover, SDF-1 increased p57kip2 expression in normal BMMNC in dose-dependent manner, but BMMNC from MDS patients showed no response to SDF-1. SDF-1-induced p57 expression was blocked by AMD3100. It is concluded that the low expression of p57 gene in MDS may play a role in the pathogenesis of MDS. Furthermore, SDF-1-induced p57kip2 expression in BMMNC, and the decreasing response of BMMNC to SDF-1 may contribute to the low expression of p57kip2 in MDS patients.
Case-Control Studies ; Chemokine CXCL12 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p57 ; genetics ; metabolism ; Flow Cytometry ; Humans ; Myelodysplastic Syndromes ; genetics ; metabolism ; Receptors, CXCR4 ; metabolism

Objective To explore the relationship between -262C/T and -21A/T polymorphisms of catalase(CAT) gene and coal-burning borne fluorosis. Methods In 2007, 150 villagers were taken as a nonintervention group in Bijie city from the village of coal-burning borne fluorosis areas with unchanged cooking stoves;150 villagers were taken as the intervention group from the town of Changchun county where cooking stoves changed; 150 villagers were taken as control from non-endemic fluorosis areas in Baiyun town of Changshun county.PCR-restriction fragment length polymorphism were employed to detect genotypes of CAT-262C/T and CAT-21A/T polymorphism of CAT gene. Results The genotypic frequencies of CAT-262C/T and CAT-21A/T in nonintervention group,intervention group and control group were in line with Hardy-Weinberg equilibrium law (P＞ 0.05 ).The genotypes of CC and CT were detected while no TT were detected for CAT-262C/T polymorphism; the genotypes of AA, AT and TT were detected for CAT-21A/T. The genotype frequencies of CAT-262 CC, CT in control group, intervention group and non-intervention group were (89.33%(134/150), 10.67%(16/150); 88.67%(133/150), 11.33% (17/150),93.33% (140/150),6.67% (10/150), respectively. The gene frequency of C in control group, intervention group and non-intervention group were (94.67% (284/300), 94.33% (283/300),96.67%(290/300), respectively. The gene frequency of T in control group, intervention group and non-intervention group were 5.33%(16/300), 5.67%(17/300), 3.33%(10/300), respectively. The genotype frequencies of CAT-21 AA,AT and TT in control group, intervention group and non-intervention group were 48.67%(73/150),46.00%(69/150),5.33%(8/150) ,52.67%(79/150) ,38.00%(57/150) ,9.33% (14/150) ,51.33%(77/150) ,38.00%(57/150), 10.67%(16/150), respectively. The gene frequency of A in control group, intervention group and non-intervention group were 71.67%(215/300),71.67%(215/300),70.33%(211/300), respectively. The gene frequency of T in control group, intervention group and non-intervention group were 28.33% (85/300),28.33% (85/300),29.67% (89/300),respectively. CAT-262C/T and CAT-21A/T genotype and allele frequencies in the control group, the intervention group and non-intervention group showed no significant differences in the distribution(x2= 0.331,0.336, all P ＞0.05 ). Conclusion CAT-262C/T and CAT-21A/T polymorphism is not associated with coal-burning borne fluorosis.