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RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
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Animals , Mice , 3' Untranslated Regions/genetics , Cell Cycle Proteins/metabolism , Gametogenesis/genetics , Meiosis/genetics , Nuclear Proteins/genetics , RNA-Binding Proteins/geneticsABSTRACT
Objective To investigate the indoor air quality in urban and rural areas in Xi'an, to analyze the relationship between indoor pollutants and living habits, and to study the impact of pollutants on health, so as to provide reference for improving indoor environment. Methods Through random cluster sampling, 29 families from rural areas and 53 families from urban areas were selected from Xi'an. Data was collected by questionnaire survey and on-site environmental sampling. Non-parametric test and Chi-square test were used for statistical analysis. Results Overall, the values of CO, NO2, toluene and xylene in Xi'an were far lower than the national standards. The medians of CO2, PM2.5, PM10, and formaldehyde were 0.1%, 44.5 μg/m3, 51.5 μg/m3, and 34.5 μg/m3, respectively. The differences in the values of CO, NO2, formaldehyde, toluene and xylene in urban and rural areas were statistically significant (P2 were higher in families with humidifiers and potted plants (P2 were higher in families with pets (P10, CO, and NO2 were significantly correlated with children's sleep duration and colds (P<0.05). Conclusion The indoor air pollution in urban areas is higher than that in rural areas in Xi'an. It is suggested that residents should be cautious about the use of humidifiers, planting potted plants, and keeping pets, to reduce indoor air pollution and improve their health.
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Objective To investigate the effects of a novel enhancer of Zeste homolog 2 (EZH2) inhibitor GSK126 in vitro on the cell proliferation and apoptosis in acute leukemia and lymphoma cells. Methods CCKˉ8 assay was used to measure the effects of GSK126 with different concentrations and time on the cell proliferation in human Tˉcell acute lymphoblastic leukemia (TˉALL) CEM cell line, acute monocytic leukemia U937 cell line and Burkitt lymphoma Raji cell line. Annexin V/PI double staining method was used to determine the effects of GSK126 on the cell apoptosis. The effect of GSK126 on the mRNA levels of EZH2, bclˉ2 and bclˉxL were measured by using quantitative polymerase chain reaction (qPCR). Results After the function for 24 h, 48 h and 72 h, compared to the negative control group (0 μmol/L), 5, 10, 15, 20, 25 μmol/L GSK126 treatment showed a significant doseˉand timeˉdependent cell proliferation suppression in CEM cells; 5, 10, 15, 20 μmol/L GSK126 treatment showed a significant doseˉand timeˉdependent cell proliferation suppression in U937 cells; 5, 10, 15, 20, 25, 30 μmol/L GSK126 treatment showed a significant timeˉdependent suppression in Raji cells (all P< 0.05). The 48 h 50% inhibitory concentration ( IC 50) of GSK126 on CEM, U937, Raji cells was (13.46 ±0.83), (11.65 ±1.02), (15.00 ±0.19) μmol/L, respectively. GSK126 treatment with the doses of 8, 12 and 16 μmol/L promoted the apoptosis of CEM and U937 cells compared with the negative control group (0 μmol/L), and there were statistical differences in the apoptosis rate (F＝ 167.995, P< 0.01; F＝ 158.400, P< 0.01). In Raji cells, only 16 μmol/L GSK126 treatment had a higher cell apoptosis rate compared with the control group (t＝ 47.998, P< 0.05). Furthermore, 8, 12 and 16 μmol/L GSK126 treatment suppressed the expressions of EZH2 mRNA in CEM, U937 and Raji cells compared with the control group (F＝82.035, P<0.01; F＝ 252.712, P< 0.01; F＝ 690.536, P< 0.01), and the expressions of bclˉ2 and bclˉxL mRNA (bclˉ2: F＝ 1 900.525, P< 0.01; F＝ 431.324, P< 0.01; F＝216.184, P<0.01; bclˉxL: F＝256.751, P<0.01; F＝147.019, P<0.01; F＝209.325, P<0.01). Conclusion EZH2 plays an important role in the occurrence and development of acute leukemia and lymphoma. GSK126 as a high selective inhibitor of EZH2 might be a potential new drug in treatment of hematological malignancies.
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Objective To study the treatment of femoral intertrochanteric fractures by reduction without a traction table in a special position and fixation with proximal femoral nail antirotation (PFNA).Methods From May 2016 to May 2017,34 patients with femoral intertrochanteric fracture were treated with PFNA.They were 20 men and 14 women,from 36 to 89 years of age (average,69.9 years).The left side was affected in 15 cases and the right side in 19.By AO classification,there were 10 cases of type AO 31-A1,13 ones of type 31-A2,and 11 ones of type 3 l-A3.Two cases were complicated with other fractures,and 5 with internal system disease,3 of whom had more than 2 concomitant diseases.Preoperative deep venous thrombosis was found in 2 cases.Surgery was performed for them between 2 and 8 days after injury (average,3.7 days).Reduction was performed in a special position without a traction table.The duration of anesthesia,operation time,intraoperative hemorrhage,postoperative complications and hip function by Harris scores were recorded.Results For the 34 patients,the anesthesia time ranged from 57 to 85 min (average,67.5 min),the operation time ranged from 28 to 65 min (average,40.9 min),and the intraoperative hemorrhage from 80 to 150 mL (average,110.6 mL).They received effective follow-up for 6 to 12 months (average,8.4 months).All the fractures healed after 6 to 12 months(average,7.2 months).No failure of internal fixation was observed during follow-ups.By the Harris scores at the final follow-up,the function of the affected hip was rated as excellent in 9 cases,as good in 21 and as fair in 4,giving an excellent to good rate of 88.2％.Conclusion In the treatment of femoral intertrochanteric fractures,reduction without a traction table in a special position and PFNA fixation may reduce anesthesia time,leading to satisfactory clinical outcomes.
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Objective To summarize and explore the morphological characteristics,genetic alterations,immunophenotype and characteristics of molecular marker of acute eosinophilic leukemia (AEL),and improve the awareness for AEL.Methods A case of refractory hematopoietic dysplasia (MDS-RCMD) transformed to AEL in our hospital was retrospectively reviewed.Results The MDS-RC-MD patient transformed to AEL in 12 months after diagnosis.In his special bone marrow 10.4％ was blasts,while 70.8％ of bone marrow cells were eosinophils including 69.3％ of promyelocyte,myelocyte and metamyelocyte.Eosinophils accounted for 13.5％ in his peripheral blood.The blasts in bone marrow expressed CD34,CD117,HLA-DR,CD33,CD38 and CD13,and accompanied by complex chromosomal abnormalities.FI1L1/PDGFRα and ETV6/PDGFRβ fusion gene were negative.The patient died two months later following treating with AML regimen.Conclusion The AEL patient with negative FI1L1/PDGFRα and ETV6/PDGFRβ gene rearrangement,imatinib treatment is ineffectual.
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Objective To observe the clinical efficacy of umbilical compress with anti-cancer Xiaogu formula in managing malignant ascites. Methods A total of 56 patients with malignant ascites who met the inclusion criteria were randomized into 28 patients in the treatment group and 28 patients in the control group. The control group was treated with one type of diuretic, and the treatment group was given umbilical compress using Anti-Cancer Xiaogu formula and diuretics. Both groups were treated for 14 days. The changes of abdominal girth, 24 h urine volume, ascites efficacy, TCM syndrome scores, quality of life and adverse reactions were observed. Results The decrease in the maximum depth difference of the ascites in the treatment group was significantly greater than that of the control group (1.16 ± 1.29 vs. 0.00 ± 1.34, Z=-2.553). The difference was statistically significant (P<0.05). The decrease in abdominal girth in the treatment group was significantly larger than that in the control group (0.57 ± 0.55 vs. 2.61 ± 0.28, Z=-2.264). The difference was statistically significant (P<0.05). The in 24-hour urine volume in the treatment group after intervention (-800.18 ± 64.12 vs.-683.57 ± 55.38, Z=-1.770) was no statistically significant (P>0.05). The response rate in the treatment group was 92.9％ (26/28), while that of the control group was 89.3％ (25/28).treatment group was 71.4％, while that of the control group was 35.7％. The difference was statistically significant (P<0.05). The increase in KPS in the treatment group was significantly higher than that of the control group. The difference was statistically significant (P<0.05). Conclusions Anti-cancer Xiaogu umbilical cord combined with diuretic can reduce the degree of malignant ascites, alleviate clinical symptoms, improve quality of life and decrease the occurrence of adverse reactions when used concomitantly with diuretics in the management of malignant ascites.
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BACKGROUND:Cervical Open-door laminoplasty with unilateral mass screw fixation and laminectomy with bilateral mass screw fixation are both procedures that treat cervical spondylotic myelopathy by expanding the space available for the spinal cord. Effectiveness and safety of two operative methods remain unclear. OBJECTIVE:To investigate the biocompatibility of implant and host between open-door laminoplasty with unilateral mass screw fixation and laminectomy with bilateral mass screw fixation to treat multi-segment cervical spondylotic myelopathy. METHODS: Data of 117 patients with multi-segment cervical spondylotic myelopathy (≥ 3 segments) were retrospectively analyzed. Sixty-five cases underwent open-door laminoplasty with unilateral mass screw fixation (laminoplasty group). Fifty-two cases underwent laminectomy with bilateral mass screw fixation (laminectomy group). Clinical outcomes were evaluated by the Japanese Orthopaedic Association scoring system and by recovery rate. Cervical curvature index and cervical range of motion were assessed by X-ray films in both groups. RESULTS AND CONCLUSION:The average folow-up time was 28 months (range 12-59 months) in both groups. No C5 nerve root palsy occurred in the two groups. Japanese Orthopaedic Association scores were greater during final folow-up than pre-fixation in both groups (P 0.05). Cervical range of motion was lower during final folow-up than pre-fixation in both groups (P < 0.01). Results confirmed that open-door laminoplasty with unilateral mass screw fixation and laminectomy with bilateral mass screw fixation have similar effectiveness in the improvement of neurological function, relieving pain and reducing complications, but wil greatly reduce the cervical range of motion.
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@#The aim of this study was to conduct the preparation and pharmaceutical characterization of a new type of terbinafine hydrochloride bioadhesive film-forming gel. The viscosity of the gel of(13 299±51)mPa ·s, pH of 3. 50±0. 50, and the shearing viscosity of(196±4)g/cm2 was found. This new gel turned out to be a layer of solid film on the application site in a very short time. The remaining solid ratio of the resulting film was estimated to be(50. 74±2. 81)%; the tensile strength was(1. 17±0. 21)MPa; and the breaking elongation was(21. 42±3. 24)%. In vitro release behavior of terbinafine hydrochloride from the film was investigated according to the paddle over disk method in ChP2010. Terbinafine hydrochloride released continuously for 10 h from the film. Improved Franz type diffusion cells were used in vitro transdermal studies by the application of excised minipigs skins. No penetration of drug into the receptor medium across the skin existed and so it could imply the safety for local application. It was found that(93. 05±5. 66)% of drug stayed on the skin surface while(1. 15±0. 85)% entered into the skin, which was beneficial for the treatment of superficial skin fungal infection.
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The dialysis for three species of poplar stems apoplast was obtained by microdialysis method, and then the concentration of Na+, K+, Ca2+ in the dialysis sample was directly measured by graphite furnace atomic absorption spectrometry ( GF-AAS) . The flow rate of perfusate was 1μL/min and the cut-off molecular weight of probe was 30 kDa. The real-time and non-destructive test technique established for the detection of ion concentration could be applied in research of poplar biochemical physiology. The recovery of the proposed method was 95. 8%-103. 1%. The contents of sodium ion in Populus wutunensis, Populus simonii and Salix matsudana were 1034-1156 μg/L, 1493-1611 μg/L and 1586-1703 μg/L; potassium ion were 1012-1237 μg/L, 941-964 μg/L and 1095-1201 μg/L; calcium ion were 4976-5237 μg/L, 4786-5042 μg/L and 5893-6142 μg/L. The method could provide reliable data for the study of ion concentration changes of plant response to adapt to all kinds of external environment.
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AIM: To study the expression and the role of ERK1/2 and JNK1/2 of MAPKs pathways in the development of neural tube defects induced by hyperthermia. METHODS: The animal models of golden hamster were produced by hyperthermia. The expression of ERK1/2 and JNK1/2, and levels of their phosphorylation were measured by Western blotting in control group and hyperthermia group. RESULTS: p-ERK1/2 steadily expressed in each control group, and the expression of p-ERK1/2 significantly decreased, which was different from that in the corresponding control group (P<0.05). The activity of p-JNK1/2 increased in hyperthermia group and the amount of p-JNK1/2 increased as compared to control group. The peak appeared at 16 h after exposed to hyperthermia (P<0.05). CONCLUSION: Hyperthermia, which induces a decrease in p-ERK1/2 expression and increases the expression of p-JNK1/2 of MAPKs pathway, results in the unbalance of cell proliferation and apoptosis, and induces neural tube defects.