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Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
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Humains , Apolipoprotéine E4/génétique , Cytosine , Mutation , Blastocyste , Hétérozygote , Édition de gène , Systèmes CRISPR-CasRésumé
Objective:To analyze the effects of stratified follow-up intervention combined with LEARNS model on self-management, glucose metabolism, compliance and satisfaction in patients with type 2 diabetes mellitus (T2DM).Methods:This study was a quasi-experimental study. A total of 212 patients with T2DM who visited the DM nursing clinic of Beijing Tiantan Hospital, Capital Medical University from June 2020 to May 2021 were selected and divided into control group (102 cases) and intervention group (110 cases) according to the treatment time. All the patients received the conventional medical treatment and health education guidance for 6 months, at the same time, the intervention group received management of the triangle stratified model combined with LEARNS mode. The glucose metabolism, self-management behavior, satisfaction and compliance were compared before and after the intervention.Results:Before the intervention, the baseline data of the 2 groups had no significant difference(all P>0.05) and were comparable. Three and six months after the intervention, the HbA1c values of the intervention group were (6.18 ± 0.57)% and (6.40 ± 0.47)%, which were significant better than those in the control group, (6.74 ± 0.90)% and (6.99 ± 0.91)%, the differences were significant ( t=8.05 and 9.12, both P<0.01). Three and six months after the intervention, the SDASC values in the intervention group were (46.51 ± 5.80) and (44.41 ± 5.61), which were higher than those in the control group, (43.45 ± 4.20) and (42.08 ± 3.67), the difference were significant ( t=6.56 and 5.32, both P<0.01). Three and six months after the intervention, the compliance and patient satisfaction of intervention group were better than those in the control group ( χ2=5.52 and 7.26, t=7.02 and 15.75, all P<0.05). Conclusions:Triangle hierarchical management combined with LEARNS model can effectively improve the blood glucose levels of T2DM patients as well as their self-management levels, satisfaction and compliance, which can help nurses reasonably allocate follow-up time.
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OBJECTIVES@#To identify whether the relationship between Zhang A, Zhang B, Zhang C and Zhang X is the half-sibling relationship whose mother is sister (hereinafter referred to as the special half-sibling relationship) or the common first cousin relationship and discuss the application of ITO method in discriminating the special kinship.@*METHODS@#DNA was extracted from blood stain of four identified individuals, PowerPlex® 21 System and AGCU 21+1 STR kit were used to detect autosomal STR genetic markers. Investigator® Argus X-12 QS kit was used to detect the X chromosome STR genetic markers, the special half-sibling index (SHSI) and first cousin index (FCI) and their likelihood ratio (LR) were calculated by ITO method.@*RESULTS@#The LR results of SHSI to FCI, which were calculated based on autosomal STR genotyping and the analysis of X-STR genotyping results suggested that the relationship between Zhang A, Zhang B, Zhang C and Zhang X was inclined to be a special half-sibling relationship.@*CONCLUSIONS@#For the identification of special kinship, it is necessary to comprehensively apply various genetic markers according to the case. After the conclusion that shared alleles cannot be excluded from the analysis, ITO method can be further used to establish discriminant assumptions according to the specific case to obtain objective and reliable identification opinions.
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Humains , Allèles , Profilage d'ADN , Famille , Marqueurs génétiques , Génotype , Répétitions microsatellites , FratrieRésumé
Objective@#To investigate the contamination, antimicrobial resistance and virulence genes of S. aureus from toilets of primary schools in Guangzhou.@*Methods@#The surface samples of toilets were collected from eight primary schools in Guangzhou from May to July 2016. The standard microbiological assays, disk diffusion methods and PCR technique were used for the isolation and identification, antimicrobial resistance and virulence genes of S. aureus .@*Results@#The contamination rate of S. aureus and MRSA was 6.25% and 3.13%, respectively. There was significant difference in the contamination rate of S. aureus among different sampling sites ( χ 2=15.15, P <0.01) and the highest contamination rate was on the ground (15.00%).The most predominant antibiotic for S. aureus was penicillin (100.00%) and the proportions of resistant to teicoplanin, erythromycin,rifampicin, clindamycin and linezolid were more than 75.00%.The multidrug resistant rate of S. aureus was 85.00%.The detection rate of virulence genes of S. aureus was sea (50.00%), tst (30.00%), etb (15.00%), eta (10.00%), seb (10.00%) and pvl (5.00%), respectively.@*Conclusion@#The contamination rate of S. aureus from toilets of primary schools in Guangzhou is in a lower level among similar researches. However, the contamination of MRSA is serious, which accounts for half of S. aureus . In addition, S. aureus isolates show high multi-drug resistant rate and high detection rate of virulence genes.
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OBJECTIVE: To collect relevant data on the development of clinical pharmaceutical services in secondary hospitals in China and analyze the existing problems of clinical pharmaceutical services and provide relevant policy suggestions. METHODS: A face-to-face interview survey was conducted to collect data on the secondary hospital clinical pharmacists′ perception of their own work, physicians′ knowledge of clinical pharmacists′ work and patient′s attitude toward clinical pharmacists′ work, et al which was analyzed with descriptive statistics tools. RESULTS: Among the clinical pharmacists, physicians, and patients surveyed, 52.8% of clinical pharmacists think that the clinical pharmacists in the hospital work smoothly, but 35.8% of clinical pharmacists think the configuration of clinical pharmacists in the hospital is unreasonable; 42.0% of the doctors had a basic understanding of the work of clinical pharmacists; the attitude of the clinical pharmacists on medication recommendations or dosing regimens was mainly partly adopted (82.5%). Most of the patients did not understand but had heard of clinical pharmacy services (39.7%).CONCLUSION: The work and assignment of clinical pharmacists, understandings between clinical pharmacists and physician, patients of secondary hospitals in China require further improvement.
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Objective To investigate hand hygiene(HH) status among health care workers(HCWs) in municipal hospitals in Chongqing City, and provide the basis for making effective HH management strategies.Methods In April-June 2016, HH status among 111 HCWs in 24 municipal hospitals of this city were investigated through questionnaire survey, on-site observation, and hand surface sampling.Results All surveyed departments are installed special hand washing facilities, all surveyed HCWs were performed HH through hand-washing by running water.The proportion of HCWs' hand-washing by disinfectant was higher than six-step hand washing (73.87% [n=82] vs 37.84%[n=42], χ2=29.23, P<0.01);the implementation rate of HH before touching patient was higher than that after touching patients (99.10%[n=110] vs 89.19%[n=99], χ2=9.88, P<0.01).During the process of diagnosis and treatment activities, the maximal total number of bacteria on the surface of hand before and after HH were 475 CFU/cm2 and 85 CFU/cm2 respectively, hand surface colony count after HH was higher than before HH(P<0.01).Age, gender, department, and occupation are important factors influencing HH.The total number of bacteria on hand surface of nurses was higher than non-nurse HCWs, the total number of bacteria on hand surface of female, nurses, and HCWs in class I environment were all higher than male, non-nurse HCWs and HCWs in other types of environment, there were significant difference among the groups (all P<0.05).Qualified rates of HH of each group improved after hand washing, the total number of bacterial colony on hands of HCWs all decreased.Conclusion Hand washing facilities and HH efficacy are good in Chongqing municipal hospitals, however,HH compliance needs to be improved among HCWs aged≥35 years,male HCWs, HCWs in class III and IV environmental departments, as well as non-nurse HCWs.
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Objective:To determine the optimal molding technology of Forsythia Suspense leaves healthy instant tea. Methods:The effects of the ratio of different excipients to dry extract powder and the concentration of wetting agent on the indices including dis-solubility, appearance and formability were investigated by single factor tests. The drying time was determined with moisture as the in-dex, and the final forming process was optimized. Results:The optimal molding progress was as follows:the ratio of dry extract powder to lactose was 1 :1. 5, and after mixed completely, 80% ethanol was used as the wetting agent to prepare wet granules, finally dried at 60℃ for 1. 5 h. Conclusion:The molding technology of Forsythia suspense leaves healthy instant tea is feasible, which can provide ref-erence for the comprehensive development and utilization of Forsythia Suspense leaves.
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Objective:To determine the optimal molding technology of Forsythia Suspense leaves healthy instant tea. Methods:The effects of the ratio of different excipients to dry extract powder and the concentration of wetting agent on the indices including dis-solubility, appearance and formability were investigated by single factor tests. The drying time was determined with moisture as the in-dex, and the final forming process was optimized. Results:The optimal molding progress was as follows:the ratio of dry extract powder to lactose was 1 :1. 5, and after mixed completely, 80% ethanol was used as the wetting agent to prepare wet granules, finally dried at 60℃ for 1. 5 h. Conclusion:The molding technology of Forsythia suspense leaves healthy instant tea is feasible, which can provide ref-erence for the comprehensive development and utilization of Forsythia Suspense leaves.
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Objective To understand the status of mobile phone use and bacterial carriage on surface of mobile phones used by health care workers(HCWs) in municipal hospitals in a city,explore the influencing factors of mobile phone use behavior and bacterial carriage status.Methods In April-June,2016,111 HCWs in 24 hospitals in a city were performed questionnaire survey,on-site observation,and sampling of mobile phone surface.Results A total of 111 (100.00%) available questionnaires were distributed and returned.The average age of the respondents were (32.00 ± 9.03)years old,female and nurses were predominant.95.50% of respondents used touch screen mobile phones,24.32% used mobile phones during diagnosis and treatment,65.77% used mobile phone >2 hours every day,93.69% cleaned and disinfected mobile phones,98.20% thought that pathogenic microorganisms exited on the surface of mobile phones.A total of 111 mobile phone surface specimens were collected,the qualified rate was 80.18%,contamination rate was 95.50%,average colony number was 2.90 CFU/cm2,the maximum bacterial content was 111.60 CFU/cm2.Among 44 specimens of mobile phone surface,55 strains of 18 species of pathogenic bacteria or opportunistic pathogenic bacteria were detected.Age,gender,and occupation were the influencing factors of mobile phone use behavior and attitude;qualified rates were all significantly different among mobile phones used by HCWs of different gender,occupation,and duration of mobile phone use (all P<0.05);bacterial contamination on the surface of mobile phones used by HCWs of different age,gender,occupation,duration of mobile phone use,and whether to use the phone shell/set were significantly different respectively(all P<0.05).Conclusion Potential pathogens on the surface of mobile phones may cause healthcare-associated infection through the use of mobile phones by HCWs during the process of medical diagnosis and treatment.
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Objective To investigate the immunization knowledge ,attitudes ,practice and requirements of the custodians of left‐behind/non‐left‐behind children in rural areas of Chongqing and to explore intervening measures .Methods Totally 1 441 com‐plete questionnaires were obtained by surveying the custodians of 1 year old left‐behind/non left‐behind children in 3 counties .Im‐munization records were checked to acquire vaccination information .Results Custodians of left‐behind children had poorer educa‐tion ,immunization knowledge and less comply with immunization behaviors than custodians of non‐left‐behind children .Village doc‐tors were essential to immunization work in rural areas .Conclusion We suggest pulling peer education in publicity and education for families with left‐behind children .It is important to mobilize the enthusiasm of village doctors ,and pay more attentions to the immunization work of left‐behind children .
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Objective To evaluate the expression of CD47 and calreticulin and their relationships with clini-copathologic features,prognosis in infiltrating ductal breast carcinomas.Methods The expression of CD47 and calret-iculin was evaluated in 128 cases with infiltrating ductal breast carcinomas by means of immunohistochemistry,and the relationship between CD47 and other clinicopathologic factors as well as prognosis were analyzed.Results The expression level of CD47 in cancer nest was 81/128,which was lower than 106/128 in its adjacent normal epithelium (χ2 =12.400,P<0.05),but calreticulin expression was 50/128 and was higher in cancer nest(χ2 =21.510,P<0.05 ).In addition,the expression level of calreticulin had certain difference in different molecular subtype (χ2 =21.510,P<0.05),and an increased expression in Basal-like and Her-(2 +)/ER(-)subtypes.The expression level of CD47 was associated with tumor sizes,histological tumor grade and lymph node involvement(χ2 =11.400, 4.732,5.432,all P<0.05),and the expression level of calreticulin was associated with histological tumor grade and distant metastasis(χ2 =10.810,6.770,all P<0.05).The 5 -year survival rate of patients performed following-up was 68.37%.Univariate analysis indicated the survival rate in 5 years of high level CD47,calreticulin expression was higher than that of low level CD47,calreticulin expression(χ2 =5.231,13.069,all P<0.05).Conclusion The expression of CD47,calreticulin is associated with index of dysprognosis and survival rate in 5 years,so combined CD47 and calreticulin detect may be of prognostic value in patients with breast caner.
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Objective To investigate the influence of in vitro artificial CO 2 cavity on matrix metallopro-teinase 2(MMP-2), adhesion molecule vascular cell adhesion molecule 1(VCAM-1), and intercellular adhesion molecule 1(ICAM-1)expression in MDA-MB-231 cell.Methods An in vitro artificial CO2 cavity model was es-tablished.MDA-MB-231 cells were exposed to CO2 under the pressure of 7 mmHg for 1, 2 and 4 hours, respective-ly.MMP-2 concentration was measured by enzyme linked immunosorbent assay (ELISA).VCAM-1 and ICAM-1 ex-pression were measured by flow cytometry 0, 24, 48 and 72 hours after CO2-insufflation.Hypoxia group was ex-posed to 0 mmHg helium for 1 h, and the control group was exposed to 37℃incubator only .Results Compared with that in the control group , MMP-2 expression in the 1, 2 and 4 hours treatment group was significantly elevat-ed at 0 hour(F=15.045, P<0.05), and the MMP-2 expression in the 2 hours CO2 treatment group was signifi-cantly elevated after 24 hours compared with that in the control group and 1, and 4 hours CO2 treatment group (F=5.976, P<0.05).The VCAM-1 expression was significantly elevated at 0 hour and after 24 hours in the 1, 2 and 4 hours CO2 treatment group compared with that in the control group ( F1 =18.321, F2 =20.443, P<0.05), and significantly declined after 72 hours in the 4 hours CO2 treatment group compared with that in 1, and 2 hours CO2 treatment group(F=15.045,P<0.05).ICAM-1 expression was significantly elevated at 0 hour in hypoxia group and 1, 2, 4 hours CO2 treatment group compared with that in the control group , Meanwhile it was higher in 2 hours CO2 treatment group than in 1 hours and 4 hours CO2 treatment group(F=73.765, P<0.05). ICAM-1 expression was significantly elevated after 24 hours in 2 and 4 hours CO2 treatment group compared with that in the control group and 1 hour CO2 treatment group(F=46.322, P<0.05), and it was significantly elevat-ed after 48 hours in 2 hours CO2 treatment group compared with that in the control group and 1, and 4 hours CO2 treatment group(F=22.315, P<0.05).Conclusion The expression of MMP-2, adhesion molecule VCAM-1, and ICAM-1 in MDA-MB-231 cells is elevated after exposure to artificial 7 mmHg CO2 cavity, and CO2 cavity of mastoscopy may modulate the metastasis capacity of breast tumor cells .
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BACKGROUND:The metastatic potential of hepatocelular carcinoma cels is key factor influencing patient’s prognosis. To observe the effect of human bone marrow mesenchymal stem cels on metastasis of hepatocelular carcinoma is of great significance for improving the lifetime of hepatocelular carcinoma patients. OBJECTIVE:To explore the biological effect of human bone marrow mesenchymal stem cels on hepatocelular carcinoma cels with different metastatic potentials. METHODS:Human bone marrow mesenchymal stem cels and hepatocelular carcinoma cel suspension with high and low metastatic potentials were respectively injected into the Transwel chamber, and after 36 hours of co-culture, ELISA method was used to detect the absorbance value as wel as cel counting method was used to observe the changes in the invasion ability of hepatocelular carcinoma cels. The effects of human bone marrow mesenchymal stem cels on the proliferation of hepatocelular carcinoma cel suspension with high and low metastatic potentials were determined using cel counting kit-8. PCR method was adopted to measure the expression of osteopontin, bone specific sialoproteins, integration (alpha V), transforming growth factor beta 1 and programmed cel death protein 5. RESULTS AND CONCLUSION:(1) The number of migrated hepatocelular carcinoma cels was significantly lower in the co-culture group than the single culture group, and based on the semi-quantitative detection of invasion ability, the absorbance value of the co-culture group was significantly lower than that in the single culture group (P 0.05). In the co-culture group with low metastatic potential, the expression of osteopontin, bone specific sialoproteins, and integration (alpha V) were declined remarkably (P 0.05). However, in the co-culture group with low metastatic potential, the expression of transforming growth factor beta 1 and programmed cel death protein 5 was both increased dramaticaly (P < 0.05). These findings suggest that the human bone marrow mesenchymal stem cels reduce the invasion ability of hepatocelular carcinoma cels, and enhance their ability of proliferation.
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BACKGROUND:The production and release of a large amount of inflammatory factors caused by immune system inflammatory response mainly contributes to secondary spinal cord injury. OBJECTIVE:To investigate the effects of umbilical cord Wharton’s jely mesenchymal stem cel transplantation on repair of injured neurological function and expression of inflammatory factors monocyte chemoattractant protein 1 and interleukin 10 in rats with acute spinal cord injury. METHODS: Eighty-one healthy adult male Sprague-Dawley rats were randomly and equaly divided into sham operation, model and cel transplantation groups, with 27 rats per group. Rats in the latter two groups were subjected to hemisection of the spinal cord to establish acute spinal cord injury models. Rat models in the cel transplantation group received umbilical cord Wharton’s jely mesenchymal stem cel injection (1×106)via the tail vein. Rat neurological function was evaluated using the BBB score at different time points after spinal cord injury. The expression of monocyte chemoattractant protein 1 and interleukin 10 in injured spinal cord tissue was detected using ELISA assay at different time points after spinal cord injury. Migration and neuronal differentiation of umbilical cord Wharton’s jely mesenchymal stem cels in the injured spinal cord tissue were determined using immunohistochemical staining method. RESULTS AND CONCLUSION:Compared with the sham operation and model groups, rat neurological function was significantly recovered in the cel transplantation group (P < 0.05). Compared to the model group, monocyte chemoattractant protein 1 level in the serum and monocyte chemoattractant protein 1 mRNA and protein expression in the injured spinal cord tissue were significantly lower (P < 0.05), but interleukin 10 mRNA and protein expression in the injured spinal cord tissue was significantly higher (P < 0.05), in the cel transplantation group. In the cel transplantation group, umbilical cord Wharton’s jely mesenchymal stem cels could migrate to the injured region and express glial fibrilary acidic protein. These findings suggest that umbilical cord Wharton’s jely mesenchymal stem cels promote rat neurological function recovery by regulating the inflammatory response in the injured spinal cord tissue, which is likely to be one of mechanisms by which transplantation of umbilical cord Wharton’s jely mesenchymal stem cels treats spinal cord injury.
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Objective To investigate the damage of mice liver and kidney with the compatibility application of Paeoniae radix rubra and Veratrum nigrum, and explore its mechanism. Methods We examined the alanine aminotransferase, aspartate aminotransferase (AST), lactic dehydrogenase, creatinine and urea nitrogen from serum, and glutathion peroxidase (GSH-Px) and malondialdehyde (MDA) from liver and kidney tissue after intragastric administration of different ratio (4∶1, 2∶1, 1∶1, 1∶2, 1∶4) of Paeoniae radix rubra and Veratrum nigrum in mice for 22 d. Results Paeoniae radix rubra used with Veratrum nigrum did not induce the obvious damage to liver with AST increase, but induced the obvious damage to kidney. At the same time, the depressed GSH-Px activity and the increased MDA content were observed in kidney tissue. When Paeoniae radix rubra and Veratrum nigrum is on a ratio of 2∶1, the kidney injury was the most obvious. Conclusion Paeoniae radix rubra used with Veratrum nigrum in varying proportions could induce the kidney injury in mice which is related to the oxidation-antioxidation balance disturbance.
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Objective To investigate the anti-HBV mechanism of oxymatrine in vitro.Methods The antiviral mechanism of oxymatrine was analyzed through detecting the expression and function of TLR9 signal pathway and the secretion of antiviral cytokines from PBMCs treated by oxymatrine in vitro.Results Oxymatrine could not only induce IFN-α and IFN-γ secretions from PBMCs directly, but also effectively augmented the expressions of TLR9, MyD88 and TRAF6 at mRNA level, and activated the TLR9 signal transduction pathway. TLR9 ligand could induce IFN-α, IFN-γ and TNF-α secretion a lot from PBMCs pretreated by oxymatrine.Conclusion Oxymatrine possesses an anti-HBV activity via activation of TLR9 signal pathway and secretion of antiviral cytokines.
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Objective To investigate the risks of HBV infection among the spouses of HBV surface antigen (HBsAg)carriers and to find out effective control strategies on hepatitis B control and prevention .Methods To use case-control study(1∶2) including spouses of HBsAg carriers aged 18 -59 years-old from the nationwide sero-epidemiological survey for Hepatitis B in Chonqing province in 2005 ,and the spouses of the healthy(HBsAg negative persons)as the control groups ,adopt euzymelinked immunosor-bent assay(ELISA) to carry out the sero-epidemiological testing (HBsAg ,anti-HBc ,anti-HBs) for Hepatitis B .Results The posi-tive rate of HBsAgamong the spouses of HBsAg carriers (14 .8% ) was higher than the rate of spouse among the healthy (7 .5% ) , with difference statistically significant (P<0 .01) ,the positive rate of HBsAg in female spouse was uptrend as the marriage age grown ,multiple factor analysis found that the risks of HBV infection among the spouses were their spouse with HBsAg and without condom when the sexual behavior .Conclusion The spouses of HBsAg carriers have high risks of HBV .Premarital examinations , safety sexual behaviors with condom ,timely hepatitis B vaccination etc .are helpful for the spouses of HBsAg carriers free of hepati-tis B virus ,especially female spouses should insist on using condom when the sexual behavior because of them easier to be infected by the hepatitis B virus .
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<p><b>OBJECTIVE</b>To explore the proliferation and invasive effects of inhibitors of kinase 4(INK4)(P15(ink4b) and P16(ink4a)/CDKN2) gene protein activation on RKO human colorectal cell in vivo and in vitro.</p><p><b>METHODS</b>RKO human colorectal cell line was exposed to the specific DNA methyltransferase inhibitor 5-Aza-CdR and INK4(P15(ink4b) and P16(ink4a)/CDKN2) protein expression was detected by Western blotting. Soft agar cloning experiment and Transwell chamber assay were used to detect the proliferative and invasive ability in vitro. Tumorigenicity in nude mice was analyzed in vivo.</p><p><b>RESULTS</b>INK4(P15(ink4b) and P16(ink4a)/CDKN2) protein expression of RKO human colorectal cells after exposure to 1×10(-7), 5×10(-7) and 1×10(-6) mol/L 5-Aza-CdR concentrations(A, B, C groups) were 1.13, 1.38, 1.92 folds and 1.11, 1.45, 2.14 folds compared to positive control group respectively. Soft agar cloning experiment showed the number of cell colony significantly decreased from 36.8±5.1(positive control group) to 32.4±7.2, 21.3±5.4 and 19.5±6.4 (3 experiment groups, all P<0.05) respectively. Transwell chamber assay showed that migrated cell number in positive control group(67.4±7.2) was significantly higher than those of 3 experimental groups(35.3±4.6, 29.5±7.3 and 25.3±6.2, respectively). The tumor volume of metastasis model in nude mice was inhibited in experimental groups, but not significantly lower compared to control group (P>0.05). There were significant differences of tumor weight and inhibition rate between control group and 3 experimental groups in nude mice respectively(all P<0.01).</p><p><b>CONCLUSION</b>INK4(P15(ink4b) and P16(ink4a)/CDKN2) protein activation can inhibit tumor proliferation, migration and suppress the tumor formation ability.</p>
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Animaux , Humains , Souris , Lignée cellulaire tumorale , Prolifération cellulaire , Tumeurs colorectales , Métabolisme , Anatomopathologie , Inhibiteur p15 de kinase cycline-dépendante , Génétique , Métabolisme , Inhibiteur p16 de kinase cycline-dépendante , Génétique , Métabolisme , Souris de lignée BALB C , Métastase tumorale , Transplantation tumorale , Activation de la transcriptionRésumé
Objective To explore the efficacy and safety of anxiety, depression, insomnia and other psychological and physical symptoms after trazodone treated in patients with alcohol dependence. Methods 100 patients whose met the inclusion and exclusion criteria were divided into trazodone group and the placebo group with a randomized, double-blind, placebo-controlled method. Each of the patients was oral trazodone, or placebo 3 times a day, each time a course of treatment was 8 weeks. Hamilton Anxiety Scale ( HAM A) , Hamilton Depression Rating Scale(HAMD) , Pittsburgh Sleep Quality Index(PSQI) , side effects scale (TESS) score and the necessary examinations were used to assess. Survey the re-drink situation after 1 year. Results 81 patients completed treatment, 19 patients were discharged or lost due to early treatment failure loss. In Trazodone group (41 cases) , the HAMA, HAMD and PSQI score before treatment and after treatment, total scores decreased gradually after 2 weeks of the three score and comfort dose group (40 cases) were the difference was statistically significant (P 0. 05 ). Conclusion Improve trazodone treat alcohol dependence withdrawal anxiety, depression and insomnia effectively. Found no adverse drug reactions and the safety is high. Reduce the recovery drink.
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<p><b>BACKGROUND</b>Increasing evidence suggests that, by the production of indoleamine 2,3-dioxygenase (IDO), dendritic cells (DC) may reduce the activity of T lymphocytes and inhibit T lymphocyte proliferation-induced immune tolerance. One promising way is inspired by increasing IDO expression in DC cells for immune tolerance after transplantation. The aim of this work was to examine the effect of interferon-γ (IFN-γ) on the expression of IDO by DC.</p><p><b>METHODS</b>Spleen-derived rat DCs were cultured and induced by cytokines, and the expression of OX62 and surface molecules CD80 and CD86 were measured with flow cytometry. After the DCs were induced by IFN-γ at different concentrations (0, 100, 300, 500 U/ml), the expression levels of IDO mRNA were measured with real-time PCR, and the expression levels of IDO protein in DCs were measured with Western blotting. The allogeneic mixed lymphocyte reaction (MLR) was used to test the effects of DCs incubated with different concentrations of IFN-γ on allogeneic T lymphocyte proliferation.</p><p><b>RESULTS</b>Under the microscope, the DCs induced by IFN-γ showed a typical dendritic morphology. The expression rate of OX62 was above 80% and the positive expression rates of CD80 and CD86 were both about 80%. The expressions of IDO mRNA and IDO protein increased gradually with the increase of IFN-γ concentration, showing statistical significance in the differences between the groups (P < 0.05). Compared with the control DC, the DC incubated with IFN-γ had a notable decrease in allostimulatory activity (P < 0.05). With the increasing IFN-γ concentration, the T lymphocyte proliferation decreased, and the difference between the groups was also statistically significant (P < 0.05).</p><p><b>CONCLUSIONS</b>The highly purified spleen derived rat DCs can be successfully acquired through the improved adhesion in-vitro method. IFN-γ can induce increased expression of IDO in spleen-derived rat DCs and reduce the spleen DCs' capacity to stimulate the proliferation of allogeneic T cells.</p>