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A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.
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Objective:To evaluate whether FOXO4-DRI could reverse radiation-induced pulmonary fibrosis (RIPF) and to explore the underlying mechanism.Methods:C57BL/6 mice were randomly divided into 4 groups: control, FOXO4-DRI, radiation, and radiation+ FOXO4-DRI. Mice in radiation or radiation+ FOXO4-DRI groups received 17 Gy X-ray radiation on the right side of the whole chest. Mice in FOXO4-DRI and radiation+ FOXO4-DRI groups were injected with FOXO4-DRI intraperitoneally at 16 and 20 weeks after irradiation, respectively. The right lungs were collected at 24 weeks after irradiation and subjected to HE staining and Masson trichrome staining to observe the morphological changes and collagen deposition. Immunohistochemistry was used to evaluate the expressions of col1α1 and α-SMA in lung tissues. β-gal staining was used to observe senescent cells. The level of reactive oxygen species in lung tissue was detected. The expressions of P21, P16 Ink4a and senescence-associated secretory phenotype (SASP) mRNA were detected by qRT-PCR, and the expression of related proteins were assessed by Western blot. Results:FOXO4-DRI reduced collagen deposition ( t=6.18, P<0.05), down-regulated the expression of col1α1 and α-SMA ( t=4.69, 3.20, P<0.05), and reduced the number of β-gal positive cells ( t=6.09, P<0.05) in the lung tissue of RIPF mice. FOXO4-DRI also down-regulated the gene and protein expressions of P21 and P16 Ink4a ( t=5.31, 3.32 and 4.77, 3.37, P<0.05) and inhibited the expressions of SASP genes IL-1α, IL-1β, TNF-α and MMP2 ( t=4.36, 4.84, 4.47, 3.82, P<0.05), reduced reactive oxygen species ( t=2.84, P<0.05), and promoted the activation of p-AKT and p-PI3K proteins ( t=-7.13, -12.61, P< 0.05) in the lung tissue of RIPF mice. Conclusions:FOXO4-DRI reverses RIPF by activating the PI3K/AKT signaling pathway, reducing oxidative stress and inhibiting cellular senescence.
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Objective:Bibliometric analysis of SCI papers in Shanghai tertiary obstetrics and gynecology specialized hospitals from 2017 to 2021 was conducted to provide reference for further improving management measures and optimizing the quality of SCI papers in specialized hospitals.Methods:The Web of Science database was used to retrieve SCI papers published by tertiary obstetrics and gynecology specialized hospitals in Shanghai from 2017 to 2021. Based on bibliometric methods VOSviwer 1.6.17 and Scimago Graphica 1.0.23 was adopted to analyze the number, journals, domestic and international cooperation, and hot research areas.Results:2 721 papers were published by Shanghai Tertiary A obstetrics and Gynecology hospitals from 2017 to 2021. These papers published in 765 journals. The number of papers published and publication journals increased year by year. The number of papers and journals with an impact factor of 3~5 is the largest, accounting for 37.96% and 35.95% of the total number of papers and journals respectively. However, papers and journals with more than 10 points accounted for only 7.98% and 10.20% respectively. Scientific Reports, a comprehensive journal, published the largest number of papers. International cooperation is concentrated in the United States. Domestic cooperation is concentrated in universities and research institutions in Jiangsu, Zhejiang and Shanghai. The hot research areas focused on Oncology, Obstetrics & Gynecology, Genetics, Reproductive Biology and other basic medical fields.Conclusions:The number of papers published by Shanghai's tertiary obstetrics and gynecology specialized hospitals has increased year by year, but there are fewer highly influential journals. Domestic and international scientific research cooperation is limited to several institutions. The achievements in the field of basic research are far more than those in clinical research.
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To address the problems existing in the ideological and political education in professional curriculum chain of obstetrics and gynecology at present, this paper suggests a design of curriculum chain which goes along the main line of ideological and political education. Surrounding the specific goal of education, this design advocates the guidance of thoughts and team building. By excavating the ideological and political elements in professional course chain, adopting the blended teaching method based on MOOC, strengthening the passing-on of value in the clinical practice of obstetrics and gynecology, this design finds out effective ways to integrate the curriculum chain of obstetrics and gynecology and ideological and political education naturally. The paper also proves the effectiveness of this model of curriculum design with a survey. This paper may provide some inspiration or reference to the future reform of ideological and political education in clinical medicine curriculum chain and the transformation of medical education model.
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Safflower(Carthamus tinctorius), a valuable traditional Chinese medicinal plant, has attracted much attention in recent years. This study established a stable tissue culture system of safflower and analyzed the chromatogram of its secondary metabolites, providing high-quality experimental materials for further research on natural products in safflower. The calluses were established from the safflower seeds germinated in a sterile environment, and then they were differentiated into the aseptic seedlings, or cultured to obtain suspension cells in liquid medium. The ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS), Progenesis QI, and principal component analysis(PCA) were used to detect and analyze the secondary metabolites in the suspension cells before and after induction with different elicitors(methyl jasmonate, silver nitrate, salicylic acid and yeast extract). A total of 23 secondary metabolites including flavonoids, phenylpropanoids, alkaloids, fatty acids and aromatic glycosides were detected in safflower suspension cells. In response to the four elicitors, 11 compounds showed increased or decreased relative content. The results indicate that different elicitors have various effects on the accumulation of secondary metabolites in safflower suspension cells, and yeast extract shows more obvious positive induction. Therefore, different elicitors may play a role in the expression of related genes in the biosynthetic pathway of specific secondary metabolites. The results facilitate the discovery of targeted elicitors and the large-scale production of valuable secondary metabolites in the future.
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Carthamus tinctorius , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Flavonoides , Glicósidos , Espectrometría de MasasRESUMEN
Recently, the hepatotoxicity issue regarding to Psoraleae Fructus (PF) has attracted remarkable concerns, which highlights the urgent need to explore the toxicity attenuation method for PF. In this study, we proposed an alcohol soaking and water rinsing method for pre-processing PF based on the record in the classics - "Lei Gong Pao Zhi Lun", aiming to attenuate the potential hepatotoxicity of PF. The optimal pre-processing methods and parameters were investigated by U*12(108) uniform design coupled with 3D-cultured human-derived liver organoids model and high-content imaging. The results showed that there were significant variations among the hepatotoxicity intensities of different pre-processed PF products. Four factors, including the concentration of alcohol, the ratio of material and alcohol in alcohol soaking, the time of alcohol soaking and the times of water rinsing, were found as independent significant factors (all P<0.01). The optimal pre-process parameters were further predicted and verified as follows: the alcohol concentration is 80%, the times of alcohol soaking is 3, the ratio of alcohol and material of alcohol soaking is 3, the time for alcohol soaking is 30 h, the ratio of water and material of water rinsing is 2, the times of water rinsing is 3, the time water rinsing is 12 h and the time of steaming is 5 h. This research demonstrated that the alcohol soaking and water rinsing method can effectively reduce the potential hepatotoxicity of PF. This method provides a reference for reducing the risk of PF liver injury from the perspective of Chinese medicinal materials pre-processing.
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Based on the theory of Q-marker, the hairy root of Salvia miltiorrhiza and S. miltiorrhiza in many provinces were studied. The relative expressions of SmCPS, SmKSL and CYP76AH1 genes in hairy roots were detected by real-time fluorescence quantitative PCR and the contents of tanshinoneⅡ_A, cryptotanshinone, tanshinoneⅠ, 1,2-dihydrotanshinone, ferruginol and miltiradiene were detected by UPLC and GC-MS, respectively. Statistical analysis shows as fllows: in the hairy root of S. miltiorrhiza, the content of miltiradiene and ferruginol is positively correlated with the content of tanshinone compounds in the downstream, and the relative expression of important genes in the biosynthetic pathway of tanshinone can reflect the content of tanshinone compounds to a certain extent; in many provinces of S. miltiorrhiza, the content of ferruginol and tanshinone compounds can also be found that there is a positive correlation between the contents. Based on the biosynthetic pathway of tanshinone compounds, which is a special index component in S. miltiorrhiza, this study focused on the important relationship between the upstream gene, the middle intermediate compound and the downstream tanshinone compound content of the biosynthetic pathway, and explored the possible research ideas of improving the quality marker system of S. miltiorrhiza, and then provided the possible research ideas for understanding and studying the quality marker of traditional Chinese medicine from the biosynthetic pathway.
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Abietanos , Vías Biosintéticas , Raíces de Plantas , Salvia miltiorrhizaRESUMEN
Objective:To examine the multiple mediating effects of cognitive fusion and network communication in the relationship between interpersonal relationship and mobile phone addiction tendency in college students.Methods:Questionnaire survey was conducted among 708 college students in a medical school using the mobile addiction tendency scale, E-communication inventory, Interpersonal relationship assessment scale and cognitive fusion questionnaire.SPSS 17.0 software was used for descriptive statistics and correlation analysis.Structural equation model was built with AMOS 21.0.The non parametric percentile bootstrap method with variance correction was used to test the significance of mediating effect.Results:(1) The sample mobile phone dependence detection rate was 13.56%.(2)There were statistical differences in conversation scores((3.49±1.85), (2.51±1.64)), making friends ((4.53±1.83), (3.21±1.72)), getting along with opposite gender((2.70±1.55), (2.01±1.60)), dealing with people disturbance(2.02(1.00, 3.00), 1.46(0.00, 2.00))between different mobile phone addiction tendency( t/ Z=2.752-5.072, P<0.05). There were statistical differences in cognitive fusion ((40.60±7.55), (33.91±7.95)) between different mobile phone addiction tendency( t/ Z=5.385, P<0.05). There were statistical differences in negative results of network communication((28.60±6.77), (23.31±7.03)), social perception of network communication((32.36±6.68), (29.17±7.82)), self exposure and emotional experience of network((23.36±6.61), (18.18±6.30)), cognition of network communication((28.19±6.85), (22.75±6.76)), entertainment of network ((6.74±1.81), (6.00±1.67)) between different mobile phone addiction tendency( t/ Z=2.647~5.195, P<0.05). (3) There was a statistically significant positive correlation between interpersonal relationship, mobile phone addiction tendency, cognitive fusion, and E-communication inventory scores ( r=0.226-0.423, P<0.01). (4) Multi-mediating model analysis showed that interpersonal relationship could affect mobile phone addiction tendency through cognitive fusion and network communication not only in a parallel way but also in a chain way.The direct effect from interpersonal relationship to mobile phone addiction tendency was 0.20, and the total indirect effect from interpersonal disturbance to mobile phone addiction tendency through cognitive fusion and network communication was 0.18.And the effects of cognitive fusion, network communication, and the chain mediating accounted for 50.0%, 33.3%, and 16.7% of the total indirect effect respectively.The 95% CI of the Bootstrap output were (0.04-0.19), (0.02-0.14)and(0.01-0.05). Conclusions:College students' interpersonal disturbances affect mobile phone addiction tendency through multiple mediations of cognitive fusion and online communication.
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Objective: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT) . Methods: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2) . Group 2 (n=96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2) . Results: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1-62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG) . The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%, the median time of neutrophil engraftment for group 1 and 2 was 16 (10-41) days vs 17 (11-33) days (P=0.705) . The ratio of platelet engraftment was 88.5% for group 1 and 87.5% for group 2, the median time of platelet engraftment was 35 (11-113) days vs 38.5 (13-96) days (P=0.317) . The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7% (95%CI 31.4%-45.9%) for group 1 and 50.0% (95%CI 39.6%-59.6%) for group 2 (P=0.075) , but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P=0.036) . Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2) : 17.7% (95%CI 11.7%-24.9%) vs 22.7% (95%CI 4.4%-32.2%) after 3 years (P=0.288) . The median follow-up time was 742 (335-2 512) days. The 3-year OS was 72.1% for group 1 and 60.5% for group 2 (P=0.079) . There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9% (95%CI 56.2%-72.3%) vs 55.4% (95%CI 44.4%-65.0%) (χ(2)=3.027, P=0.082) ]. Non-relapse mortality for group 1 was 12.1% (95%CI 7.7%-17.4%) and for group 2 was 16.7% (95%CI 10.0%-24.8%) (P=0.328) . Conclusion: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.
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Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto Joven , Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Antígenos HLA , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Recurrencia Local de Neoplasia , Receptores KIR , Estudios RetrospectivosRESUMEN
Objective To investigate whether cyclic GMP-AMP synthase ( cGAS ) , a cytosolic DNA sensor, could recognize the reverse transcription intermediate and induce the subsequent signaling path-way during the infection of human T cell leukemia virus type 1 ( HTLV-1 ) . Methods Biotin-labeled ssDNA90, a reverse transcription intermediate of HTLV-1, was transfected into HeLa cells and the interac-tion between it and cGAS was detected by co-immunoprecipitation experiments. HeLa cells were co-cultured with HTLV-1-positive MT2 cells and the interaction between cGAS and stimulator of interferon genes ( STING) was analyzed by co-immunoprecipitation experiments. The expression of STING in HeLa cells was silenced by siRNA. cGAS was transfected into the HeLa cells 24 h after the silencing and after 24 h, these cells were co-cultured with MT2 cells for another 24 h. Real-time PCR assay was used to measure the ex-pression of IFN-β, RANTES ( regulated upon activation, normal T-cell expressed, and secreted) , TNF-α, HTLV-1 protein Tax, p19 and HBZ. Immunoblot assay was performed to evaluate the phosphorylation of IRF3 and p65 in HeLa cells. Results cGAS interacted with ssDNA90. cGAS interacted with STING in the cytoplasm. In STING-silenced HeLa cells, cGAS transfection had no influence on the expression of IFN-β, RANTES , TNF-α, Tax , p19 or HBZ , nor did it affect the phosphorylation of IRF3 or p65 . Conclusions cGAS interacted with HTLV-1 RTI ssDNA90 and activated STING-dependent innate immune responses.
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OBJECTIVE@#To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT).@*METHODS@#Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen,and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD.@*RESULTS@#The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)>0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival.@*CONCLUSION@#UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.
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Humanos , Trasplante de Células Madre de Sangre del Cordón Umbilical , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Enfermedad Injerto contra Huésped , Leucemia Mieloide Aguda , Ácido Micofenólico , Proteínas de Fusión Oncogénica , Trasplante de Células Madre de Sangre Periférica , Proteína 1 Compañera de Translocación de RUNX1 , Acondicionamiento PretrasplanteRESUMEN
Objective To explore the effect of simvastatin combined with cyclosporin A treatment on the development of obliterative bronchiolitis in a murine heterotopic tracheal transplantation model .Methods Murine tracheals were heterotopically transplanted from BALB/c donors into C57BL/6 recipients .Transplanted animals received either control chow ,chow containing simvastatin ,chow containing cyclosporine A ,or chow containing simvastatin and cyclosporine A . beginning immediately after transplantation .Epithelial loss and luminal obstruction were analyzed by morphometry .Immunohistochemistry assay was used for quantifying inflammatory cell infiltration and expression of chemokine in tracheal allografts .collagen deposition was studied by picro sirius red staining .Group t test was used to calculate the difference between groups .Results simvastatin combined with cyclosporin A treatment reduced chemokine (MCP-1 , RANTES ) release , inhibited CD4+ and CD8+ T cells and macrophages accumulation in tracheal allografts ,resulting in limited bronchial inflammation and diminished epithelial loss .simvastatin plus cyclosporin A treatment also inhibited proliferation of myofibroblast cells ,reduced M M P-2 release and decreased the amounts of type I and III collagen deposition ,resulting in preserved luminal patency and inhibited development of OB compared with those of controls .Conclusions When simvastatin was used in combination with CsA ,the development of OB was significantly inhibited .
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Objective@#To explore the effect of simvastatin combined with cyclosporin A treatment on the development of obliterative bronchiolitis in a murine heterotopic tracheal transplantation model.@*Methods@#Murine tracheals were heterotopically transplanted from BALB/c donors into C57BL/6 recipients. Transplanted animals received either control chow, chow containing simvastatin, chow containing cyclosporine A, or chow containing simvastatin and cyclosporine A. beginning immediately after transplantation. Epithelial loss and luminal obstruction were analyzed by morphometry. Immunohistochemistry assay was used for quantifying inflammatory cell infiltration and expression of chemokine in tracheal allografts. collagen deposition was studied by picro sirius red staining.Group t test was used to calculate the difference between groups.@*Results@#simvastatin combined with cyclosporin A treatment reduced chemokine(MCP-1, RANTES)release, inhibited CD4+ and CD8+ T cells and macrophages accumulation in tracheal allografts, resulting in limited bronchial inflammation and diminished epithelial loss. simvastatin plus cyclosporin A treatment also inhibited proliferation of myofibroblast cells, reduced MMP-2 release and decreased the amounts of type I and III collagen deposition, resulting in preserved luminal patency and inhibited development of OB compared with those of controls.@*Conclusions@#When simvastatin was used in combination with CsA, the development of OB was significantly inhibited.
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Objective: To prepare nerve growth factor(NGF) temperature sensitive in situ gel and investigate its therapeutic effect on sciatic nerve injury of rats.Method: NGF thermosensitive gel was prepared and its prescription was optimized by central composite design-response surface methodology.Fifty rats were randomly divided into the normal group,model group,NGF injection group(10 mg·L-1),NGF low-dose(10 mg·L-1) and high-dose(20 mg·L-1) thermosensitive gel groups,and sciatic nerve injury model of rats was established.The effect of NGF thermosensitive gel on the injury of sciatic nerve were comprehensively examined by taking rat behavior,sciatic nerve function index(SFI),time of withdrawal reflex,wet weight ratio of gastrocnemius muscle,and histomorphological changes as indicators.Result: The gelation temperature of NGF thermosensitive gel was 35.2℃ after the formulation being optimized,which was in line with the standard for injection.Four-eight weeks after operation,the SFI and wet weight ratio of gastrocnemius muscle in rats of NGF high-dose thermosensitive gel group were significantly higher than those in the model group and NGF injection group,but its time of withdrawal reflex was significantly lower than those in the model group and NGF injection group,and the effect was in a dose-dependent manner.Arrangement of regenerated nerve fibers in sciatic nerve injury area of rats from NGF high-dose thermosensitive gel group was more tidy,dense and continuous than that of the model group.Conclusion: NGF thermosensitive gel can promote repair of sciatic nerve injury in rats.
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Objective: To compare the clinical efficacy of umbilical cord blood transplantation (UCBT) and hematopoietic stem cell transplantation from HLA-matched sibling donors (MSD-HSCT) in the treatment of myelodysplastic syndrome-EB (MDS-EB) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) . Methods: A cohort of 64 patients (including 38 cases of MDS-EB and 26 cases of AML-MRC) who received UCBT/MSD-HSCT from February 2011 to December 2017 were retrospectively analyzed. Results: ①Compared with MSD-HSCT group, UCBT group had a higher proportion of AML-MRC patients [52.8% (19/36) vs 25.0% (7/28) , P=0.025], and a lower median age [13 (1.5-52) years vs 32 (10-57) years, P=0.001]. ②The engraftment of neutrophils both in UCBT and MSD-HSCT groups on +42 d was 100%, and the median engraftment time was 17.5 (11-31) d and 11.5 (10-20) d, respectively. The engraftment of platelet at +100 d in UCBT group was 91.4%, the median engraftment time was 40 (15-96) d; The engraftment of platelet at +100 d in MSD-HSCT group was 100%, and the median engraftment time was 15 (11-43) d. ③There were no statistically significant differences in terms of the cumulative incidence of Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD of 100 d and transplant related mortality (TRM) of 180 d, relapse rate, overall survival (OS) , disease-free survival (DFS) between UCBT and MSD-HSCT groups (P>0.05) . ④The 3-year cumulative incidence of chronic GVHD (cGVHD) and severe chronic GVHD in UCBT group were lower than of MSD-HSCT group [28.3% (95%CI 13.4%-45.3%) vs 67.9% (95%CI 46.1%-82.4%) , P=0.002; 10.3% (95%CI 2.5%-24.8%) vs 50.0% (95%CI 30.0%-67.1%) , respectively, P<0.001]. The cumulative 3-year incidence of GVHD-free and relapse-free survival (GRFS) of UCBT group was significantly higher than of MSD-HSCT group [55.0% (95%CI 36.0%-70.6%) vs 28.6% (95%CI 13.5%-45.6%) , P=0.038]. Conclusion: UCBT could obtain better quality of life after transplantation than MSD-HSCT in treatment of MDS-EB/AML-MRC.
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Adolescente , Adulto , Humanos , Persona de Mediana Edad , Adulto Joven , Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/terapia , Calidad de Vida , Estudios Retrospectivos , HermanosRESUMEN
MCT is an important key enzyme in the terpenoid biosynthesis in MEP pathway. In this study, Gateway technology was used to construct RNAi vector of TwMCT, and a vector fragment with a size of 484 bp was obtained. The TwMCT RNAi vector was transferred into the suspension cells of Tripterygium wilfordii by gene gun. Accumulation of terpenoids was assayed by UPLC, and the result showed that the content of triptolide and celastrol in cells decreased by 23.4% and 42.8%, respectively, compared with the control group pK7GWIWG2D. Moreover, the gene expression of TwMCT and major genes in terpenoid biosynthesis pathway was detected by qRT-PCR, which demonstrated that the expression of TwMCT reduced by 29.2% relative to that of the control group pK7GWIWG2D, and the relative expression of TwDXR, TwGGPS, TwHMGR and TwHMGS diminished by 36.3%, 31.3%, 62.2%, and 29.1%, respectively, but the expression of TwDXS was up-regulated by 114.2%, and there was no significant change in TwFPS. Thus, it was verified in vivo that interference with TwMCT expression significantly inhibited the accumulation of triptolide and celastrol in Tripterygium wilfordii, laying a foundation for further exploring the regulation mechanism of MCT gene on the terpenoid biosynthesis in Tripterygium wilfordii.
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Objective To compare diagnostic accuracy of spiral CT with low dose scanning to normal dose scanning for chronic obstructive pulmonary disease(COPD)and to evaluate clinical application for COPD diagnosis.Methods A total of 120 patients were recruited with a primary diagnosis of COPD,and detailed symptoms and medical history were recorded when patients were hospitalized.These patients were then randomized into two groups and examined with low dose or normal dose CT scanning,respectively.Image quality and effective radiation dose of the two groups were measured and clinical diagnosis of COPD was used as gold standard to assess diagnostic accuracy of low dose scanning for COPD.Results No significant difference on imaging quality was detected between the two groups in our study.However,effective radiation dose in low dose group was only (1.24±0.18)mSv,much lower than that in normal dose group with an effective radiation dose of(3.31±0.52)mSv.The sensitivity of normal dose scan for COPD diagnosis was 87% and the specificity was 57%.Though there was no significant difference between the two groups in diagnostic accuracy,both the sensitivity (92%)and the specificity(80%)of low dose scanning for COPD showed slight inclination.Conclusion Spiral CT with low dose dynamic scanning presented equal diagnostic value,but lower radiation dose for COPD patients,compared to normal dose scanning,which is worth for clinical application.
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The purpose of this study was to investigate the effects of ubiquitin C-terminal hydrolase-L1 (UCHL1) on non-small cell lung cancer cell line A549. UCHL1 gene knockout A549 cell line was constructed by CRISPR-CAS9 gene editing technique. The mRNA and protein levels of UCHL1 were examined by RT-PCR and Western blot, respectively. Cell proliferation and cycles were analyzed by CCK-8 method and flow cytometry, respectively. The sensitivity of A549 cells to cisplatin was detected by CCK-8 method. Migration ability of A549 cells was detected by scratch assay and Transwell test, and p-Erk expression level was assessed by Western blot. The results showed that UCHL1 gene knockout A549 cells were successfully constructed by CRISPR-CAS9 gene editing technique. After UCHL1 gene knockout, there was no significant change in cell proliferation and cell cycle ratios in A549 cells. UCHL1 gene knockout A549 cells exhibited decreased sensitivity to cisplatin and migration activity, as well as increased p-Erk expression level. These results suggest that the loss of UCHL1 gene function may reduce the sensitivity and migration ability of A549 cells, and this effect may be related to the activation of Erk1/2 signaling pathway.
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Objective To investigate the role of cyclic GMP-AMP synthase (cGAS),a cytosolic DNA sensor,in regulating innate immune responses induced by reverse transcription intermediate of human T cell leukemia virus type 1 (HTLV-1). Methods (1)ssDNA90,the reverse transcription intermediate of HTLV-1,was transfected into HeLa cells to observe changes in the expression pattern of cGAS in transfected-HeLa cells with immunoblot assay. (2) HeLa cells were firstly transfected with cGAS-encoding plasmid and then ssDNA90 24 hours later. Real-time PCR was used to measure the expression of interferon ( IFN)-β, IFN-gamma-inducible protein 10 ( IP-10 ), regulated on activation, normal T cell expressed and secreted (RANTES) and tumor necrosis factor (TNF)-α. Immunoblot assay was performed to measure phosphorylated interferon regulatory factor 3 (IRF3) and p65. (3)cGAS expression was silenced by siRNA in HeLa and phorbol-12-myristate-13-acetate (PMA)-treated THP1 (PMA-THP1) cells and then ssDNA90 was transfect-ed into these cells 24 hours later. Real-time PCR was used to measure the expression of IFN-β,IP-10,RAN-TES and TNF-α. Immunoblot assay was performed to measure phosphorylated IRF3 and p65. Results Ex-pression of cGAS was increased in HeLa cells after ssDNA90 transfection. Compared with control cells, cGAS-transfected HeLa cells showed increased expression of IFN-β, IP-10, RANTES and TNF-α and en-hanced phosphorylation of IRF3 and p65 after ssDNA90 transfection. Compared with control cells,both HeLa and PMA-THP1 cells with silenced expression of cGAS showed impaired production of IFN-β,IP-10,RAN-TES and TNF-α after ssDNA90 transfection. Moreover,ssDNA90-induced phosphorylation of IRF3 and p65 were decreased after cGAS gene-knockdown. Conclusion cGAS might promote HTLV-1 RTI ssDNA90-in-duced innate immune responses.
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Objective: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of refractory and relapsed acute leukemia (AL) patients. Methods: The clinical data of 22 refractory and relapsed AL patients who were treated with UCBT as salvage therapy from November 2009 to May 2017 were retrospectively analyzed. All patients received a myeloablative conditioning regimen for prevention of graft-versus-host disease (GVHD) with cyclosporine A (CSA)/short course of mycophenolate mofetil (MMF). Results: ①Of 22 patients, 9 cases were male and 13 female. The median age was 23 (15-44) years and median weight of 52.5 (43-82) kg. All patients were transplanted with a median umbilical cord blood nucleated cells of 3.07 (1.71-5.30)×107/kg (by weight), the median CD34+ cells was 1.60 (0.63-3.04)×105/kg (by weight). ②The myeloid cumulative implantation rate was 95.5% (95%CI 45.2-99.7%) after transplantation of 42 d, with the median implantation time of 19 (13-27) d. The platelet cumulative implantation rate after transplantation of 120 d was 81.8% (95%CI 54.2-93.6%), the median implantation time of 42 (20-164) d. ③The incidence of Ⅱ-Ⅳ, Ⅲ-Ⅳ aGVHD and the 2 year cumulative incidence of cGVHD were 36.4%, 13.6% and 40.3% respectively. ④ The transplant related mortality (TRM) after transplantation of 180d was 22.7%, 2 year cumulative rate of relapse was 18.7% (95%CI 3.6-42.5%), 2 year disease-free survival rate (DFS) and overall survival rate (OS) were 53.7% and 58.1%, respectively. Conclusion: The preliminary results show that the use of UCBT is safe and effective for refractory and relapsed AL patients who fail to respond to conventional chemotherapy.