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ObjectiveThis research focused on examining the distinctive characteristics of nutrient intake and dietary patterns among long-lived elderly individuals. Additionally， the study was aimed to explore the specific dietary components that may impact the skeletal muscle mass in this particular group. MethodsThis study was conducted in the Chongming area of Shanghai， China. A total of 206 long-lived elderly individuals aged 90 or above were recruited. The 3-day 24-hour dietary recall method was used to collect dietary information and general demographic data through face-to-face interviews with professional nutritionists. The skeletal muscle mass index（SMI） was measured by bioelectrical impedance analysis（BIA）， and low skeletal muscle mass was diagnosed based on the 2019 Asian Working Group for Sarcopenia criteria. T-test analysis， chi-square test， and logistic regression were used to analyze the relationship between dietary nutrient intake and skeletal muscle mass. ResultsIn terms of food intake categories， compared with the long-lived elderly people with normal muscle mass， the intake of cereals containing miscellaneous beans and vegetables in the long-lived elderly people with low muscle mass was significantly lower（P<0.05）. In terms of the nutrient intake， compared with the long-lived elderly people with normal muscle mass， the intake of total energy， carbohydrate， dietary fiber， vitamin D， folic acid， phosphorus， potassium， magnesium， iron， and manganese in the long-lived elderly people with low muscle mass was significantly lower（P<0.05）. After continuous adjustment for the covariates， multivariate logistic regression analysis found that the intake levels of folic acid and dietary fiber were important factors influencing skeletal muscle mass， Individuals with lower intake levels of folic acid and dietary fiber are at a higher risk of low muscle mass in long-lived elderly individuals ［ORfolic acid T1， dietary fiber T1 （95%CI）： 2.90 （1.11‒7.61）； 4.09 （1.53‒10.91）］. ConclusionThe consumption of cereals that include a variety of beans and vegetables was noticeably lower in the long-lived elderly individuals with lower muscle mass when compared to those with normal muscle mass. Furthermore， low levels of folic acid and dietary fiber intake are associated with an increased risk of low skeletal muscle mass.
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Objective To investigate the application value of single nucleotide polymorphism(SNP)linkage analysis based on next-generation sequencing(NGS)technology in preimplantation genetic testing(PGT)of families with autosomal recessive polycystic kidney disease(ARPKD).Methods A family with ARPKD was selected,where the female member had a pregnancy ultrasound revealing polycystic kidney in the fetus.Genetic testing showed compound heterozygous mutations of the polycystic kidney/polycystic liver disease 1 gene(PKHD1),c.10444C>T(paternal)and c.4303del(maternal),with the c.4303del mutation being reported for the first time.Targeting the coding region of the PKHD1 gene,335 high-density tightly linked SNP sites were selected in the upstream and downstream 2M regions using multiplex polymerase chain reaction(PCR)and NGS.The couple′s SNP risk haplotypes carrying gene mutations were constructed.After in vitro fertilization,blastocyst culture was performed.Trophoblastic cells obtained from the biopsy were subjected to whole-genome amplification,and NGS was used for linkage analysis and low-depth chromosomal aneuploidy screening of the embryos.Sanger sequencing was used to verify the results of embryo linkage analysis.Results Among the 6 biopsied embryos,4 were mutation-free and euploid,1 exhibited heterozygous for the mutation and mosaic while another unstable sequencing data,making it impossible to judge.One of the mutation-free and developmentally healthy euploid embryos was implanted into the maternal uterus,resulting in the full-term delivery of a healthy baby.Conclusion Application of NGS-based SNP linkage analysis in PGT can effectively blocking the vertical transmission of ARPKD within families,while avoiding abortion issues caused by aneuploid embryos.This study is also the first PGT report target-ing the PKHD1 gene c.4303del mutation.
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Objective @#To analyze the pregnancy outcome of preimplantation genetic testing for aneuploidy (PGT-A) in cycles with different indications．@*Methods @#The clinical information of 549 couples who underwent PGT-A were retrospectively analyzed．The cycles were divided into 6 groups according to the indication for PGT-A，namely : recurrent pregnancy loss group(n = 304) ，repeated implantation failure group(n = 57) ，advanced age group( ≥38 years old，n = 80) ，history of adverse pregnancy group(chorionic trisomy or adverse pregnancy，n = 24) ，male factor infertility group (n = 67) ，and abnormal sex chromosome number group (n = 17) ．The basic information，the number of retrieved oocytes，embryo biopsy result and pregnancy outcome were compared among different indication groups. @*Results@#The average age and days of gonadotropin ( Gn) used among the six groups were statistically different (P＜0. 001) ．The average number of retrieved oocytes，the rate of good-quality embryos，mosaic embryos， abnormal embryos and normal embryos，the average ovarian sensitivity index ( OSI) among the six groups were statistically different (P = 0. 03，P ＜0. 001，P = 0. 03，P ＜0. 001，P ＜0. 001，P ＜0. 001 ) ．Advanced age group had the highest rate of abnormal embryos，the least average number of retrieved oocytes，the lowest OSI and the lowest rate of normal embryos．There were statistical differences in clinical pregnancy rate，ongoing pregnancy rate and cumulative pregnancy rate per oocyte retrieved cycle (P＜0. 001) among the six groups，but there were no statistical differences in clinical pregnancy rate，ongoing pregnancy rate per transfer cycle and cumulative pregnancy rate among the five groups except for the male factor infertility group．@*Conclusion@#PGT-A can detect euploid embryo to transfer thereby improving pregnancy efficiency．The advanced age women have normal embryo to transfer and can obtain a better pregnancy rate，which may shorten their time of“take- baby -home ”．At the same time， PGT-A can significantly improve the pregnancy outcome of those with male factor infertility.
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【Objective】 To explore the pathogenesis of fetal edema caused by CD36 antibody in fetal/neonatal alloimmune thrombocytopenia (FNAIT), and to provide reference for clinical prevention and treatment. 【Methods】 The established CD36 monoclonal antibody was incubated with human peripheral blood mononuclear cells (PBMC), and the concentrations of cytokines (TNF-α and IL-1β) in the supernatant of cell culture were detected by ELISA. The permeability of endothelial cells were investigated by detecting the fluorescence intensity of FITC-albumin by incubating cytokine-rich cell supernatant with human umbilical vein endothelial cells (HUVEC). 【Results】 Flow cytometry showed that CD36 monoclonal antibody could bind to human monocytes. Compared with isotype IgG control, increased cytokine TNF-α (pg/mL) (407.73±20.40 vs 29.38 ±4.72, P<0.05) and IL-1β (pg/mL) (247.14±83.59 vs 53.68±26.96, P<0.05) were detected in the supernatant of cell culture after incubation of CD36 monoclonal antibody with human PBMC. Detection of fluorescence intensity of FITC-albumin in transwell cultured HUVEC showed that cytokine-rich cell supernatant derived from CD36 monoclonal antibody incubated with human PBMC can increase the permeability of endothelial cells significantly (CD36 antibody vs isotype IgG, MFI value: 492±16 vs 320±11, P<0.05). 【Conclusion】 The effect of CD36 monoclonal antibody on PBMC can increase HUVEC permeability, which may be one of the pathogenesis of fetal edema with FNAIT.
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Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi, of which cycloastragenol-type glycosides are the most typical and major bioactive compounds. This kind of compounds exhibit various biological functions including cardiovascular protective, neuroprotective, etc. Owing to the limitations of natural sources and the difficulties encountered in chemical synthesis, re-engineering of biosynthetic machinery will offer an alternative and promising approach to producing astragalosides. However, the biosynthetic pathway for astragalosides remains elusive due to their complex structures and numerous reaction types and steps. Herein, guided by transcriptome and phylogenetic analyses, a cycloartenol synthase and four glycosyltransferases catalyzing the committed steps in the biosynthesis of such bioactive astragalosides were functionally characterized from Astragalus membranaceus. AmCAS1, the first reported cycloartenol synthase from Astragalus genus, is capable of catalyzing the formation of cycloartenol; AmUGT15, AmUGT14, AmUGT13, and AmUGT7 are four glycosyltransferases biochemically characterized to catalyze 3-O-xylosylation, 3-O-glucosylation, 25-O-glucosylation/O-xylosylation and 2'-O-glucosylation of cycloastragenol glycosides, respectively. These findings not only clarified the crucial enzymes for the biosynthesis and the molecular basis for the structural diversity of astragalosides in Astragalus plants, also paved the way for further completely deciphering the biosynthetic pathway and constructing an artificial pathway for their efficient production.
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Objective:To explore the effects of miR-451 on glycolysis and apoptosis of breast cancer cells by regulating the Rho/ROCK1 pathway.Methods:Breast cancer MCF7 cells were divided into breast cancer cells (BC) group, breast cancer cells + miR-451-NC (MN) group, breast cancer cells + miR-451 inhibitor (MI) group, breast cancer cells + miR-451 mimic (MM) group, breast cancer cells + lysophosphatidic acid (BL) group, breast cancer cells + fasudil (BF) group, and breast cancer cells + miR-451 mimic + fasudil (MF) group. Glucose uptake detection kit and lactate detection kit were used to detect cell glycolysis, DAPI staining was used to detect cell apoptosis, Western blotting was used to detect Rho/ROCK1 pathway protein expression, and double luciferase reporting assay was used to confirm the interaction between miR-451 and Rho/ROCK1.Results:The glucose intake of cells in the BC group, MN group, MI group and MM group were (14.22±2.36) ×10 5 mg/h, (14.20±2.37) ×10 5 mg/h, (21.55±2.43) ×10 5 mg/h, (6.19±1.34) ×10 5 mg/h ( F=5.30, P<0.001), respectively, and lactic acid production were (1.52±0.21) ×10 5 μg/h, (1.53±0.22) ×10 5 μg/h, (2.05±0.32) ×10 5 μg/h, (0.54±0.12) ×10 5 μg/h ( F=3.28, P=0.008), respectively. The apoptosis rates were (10.13±1.35) %, (10.16±1.37) %, (5.36±1.24) %, (28.47±2.56) % ( F=6.36, P<0.001), respectively. The expressions of Rho protein were 2.31±0.46, 2.32±0.41, 2.95±0.35, 1.05±0.25 ( F=2.86, P=0.017), respectively. The expressions of ROCK1 protein were 2.51±0.41, 2.52±0.42, 3.05±0.33, 1.15±0.13 ( F=2.43, P=0.035), and there were statistically significant differences between the MN and MI groups, MN and MM groups, MI and MM groups (all P<0.05). The glucose intake in the BC group, BL group and BF group were (14.22±2.36) ×10 5 mg/h, (21.54±2.40) ×10 5 mg/h, (6.20±1.35) ×10 5 mg/h ( F=5.33, P<0.001), respectively. Lactic acid production were (1.52±0.21) ×10 5 μg/h, (2.01±0.30) ×10 5 μg/h, (0.55±0.12) ×10 5 μg/h ( F=3.28, P=0.008), respectively. The apoptosis rates were (10.13±1.35) %, (5.34±1.22) %, (28.44±2.54) % ( F=6.45, P<0.001). The expressions of Rho protein were 2.31±0.46, 2.94±0.45, 1.01±0.24 ( F=2.40, P=0.037), respectively, and the expressions of ROCK1 protein were 2.51±0.41, 3.08±0.42 and 1.13±0.12, respectively ( F=2.38, P=0.039). The pairwise comparisons among the three groups were statistically significant (all P<0.05). In the MF group, glucose intake was (3.21±0.89) ×10 5 mg/h, lactic acid production was (0.33±0.04) ×10 5 μg/h, apoptosis rate was (38.01±2.87) %, Rho protein expression was 0.55±0.14, and ROCK1 protein expression was 0.51±0.10. There were statistically significant differences among the MM group, BF group and MF group ( F=4.53, P=0.001; F=4.26, P=0.002; F=6.12, P<0.001; F=4.06, P=0.002; F=9.72, P<0.001), and there were statistically significant differences between the MF group and BF group (all P<0.05). Dual luciferase report showed that miR-451 transfection significantly decreased the luciferase activity of ROCK1-3'-UTR-WT (0.59±0.03 vs. 1.01±0.05, t=17.64, P<0.001), but had no significant effect on mutated genes (1.01±0.07 vs. 1.02±0.04, t=0.30, P=0.767) . Conclusion:Overexpression of miR-451 can significantly inhibit glycolysis of breast cancer cells and promote apoptosis of breast cancer cells, the mechanism of which may be related to inhibition of Rho/ROCK1 pathway.
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Objective:To investigate the driving effect of prostate cancer associated transcript 4 (PCAT4) on the up-regulation of upregulator of cell proliferation (URGCP) expression in breast cancer progression through sponging miR-508-5p.Methods:The microarray data of lncRNA and miRNA with differential expression in breast cancer tissue were analyzed by Cancer Genome Atlas. The expression of PCAT4 in breast cancer was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was measured by MTT and colony formation, cell apoptosis was analyzed by TUNEL, and cell migration and invasion were analyzed by Transwell. The correlation between PCAT4 and miR-508-5p, and miR-508-5p and URGCP was analyzed by RNA pull-down and double luciferase assay. Tumor xenograft studies were performed to analyze the correlation between PCAT4/miR-508-5p/URGCP axis and breast cancer cell growth in vivo. Measurement data were expressed as mean ± standard deviation ( ± s). T-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups. The correlation between PCAT4 and URGCP and miR-508-5p expression was evaluated by Pearson correlation analysis. Results:The expression level of PCAT4 was up-regulated in breast cancer tissues and cells. Knockout of PCAT4 inhibited cell proliferation and metastasis and promoted cell apoptosis. miR-508-5p was the target of PCAT4 and was negatively correlated with PCAT4. Overexpression of miR-508-5p in breast cancer can inhibit cell growth, migration and invasion, and promote cell apoptosis. URGCP is the target of miR-508-5p and induces progression of breast cancer. Tumor xenograft studies showed that PCAT4 drives breast cancer progression by affecting miR-508-5p/URGCP.Conclusion:The expression of PCAT4 is up-regulated in breast cancer tissues and cells, and PCAT4 can act as a molecular sponge of miR-508-5p, and significantly promote breast cancer progression by activating URGCP protein expression.
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【Objective】 To investigate whether the blood donors' coagulation status may lead to apheresis platelet aggregation in vitro. 【Methods】 Thirty blood donors with aggregation in apheresis platelets collected by AMICUS blood cell separator no less than 3 times previously and occurred when the last time of apheresis donation were observed in aggregated group (referred to as the experimental group); Thirty donors without aggregation in apheresis platelets collected by AMICUS blood cell separator no less than 3 times were observed in the control group simultaneously. The basic platelet parameters in the two groups, including Plt, MPV, PDW, Pet, P-LCR were detected by automatic blood cell analyzer (BC-3000Plus), and thromboelastogram indexes including reaction time(R), kinetics time(K), kinetics of clot development(α), maximum amplitude (MA) and coagulation index(CI) were tested by Thrombosis elastography (TEG) before collection. With SPSS24.0 software, t test was used to compare the differences between the two groups. 【Results】 The CI value in experimental group was significantly different from that of the control group (0.48± 1.00 vs -0.99 ±1.96, P0.05 ) . 【Conclusion】 The coagulation status of blood donors may be an independent risk factor for the in vitro aggregation of apheresis platelets.
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Antibodies against human CD36 are responsible for several immune-mediated disorders. The detection of anti-CD36 antibodies using the standard monoclonal antibody (mAb) immobilization of platelet antigens (MAIPA) assay is hampered by a high frequency of false-negative results, most likely due to competitive inhibition of the mAb used as the capture antibody. We generated a panel of mouse mAbs against CD36 and seven hybridomas (GZ-3, GZ-13, GZ-70, GZ-143, GZ-413, GZ-507, and GZ-608), which were selected for MAIPA assays, as they reacted with mouse and human CD36. Fourteen anti-CD36 sera were assayed; all of which showed a positive reaction in a PakPlus (Immucor GTI Diagnostics, Inc., Waukesha, WI, USA) ELISA-based screening (optical density: 0.257–2.292). When the reference anti-CD36 mAb FA6-152 was used in the MAIPA assay, only 6/14 (42.9%) sera displayed a positive reaction. In contrast, anti-CD36 antibodies were detected in 13/14 (92.9%) sera when GZ-70 and GZ-608 mAbs were used. This significant improvement resulted in the identification of anti-CD36 antibodies by an antigen capture assay. Since patient’s platelets possibly carrying rare native antigens are used, this method will facilitate the identification of new platelet antibodies against CD36 that are involved in immune-mediated thrombocytopenia and other diseases, such as transfusion-related acute lung injury.
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Bibenzyls, a kind of important plant polyphenols, have attracted growing attention for their broad and remarkable pharmacological activities. However, due to the low abundance in nature, uncontrollable and environmentally unfriendly chemical synthesis processes, these compounds are not readily accessible. Herein, one high-yield bibenzyl backbone-producing Escherichia coli strain was constructed by using a highly active and substrate-promiscuous bibenzyl synthase identified from Dendrobium officinale in combination with starter and extender biosynthetic enzymes. Three types of efficiently post-modifying modular strains were engineered by employing methyltransferases, prenyltransferase, and glycosyltransferase with high activity and substrate tolerance together with their corresponding donor biosynthetic modules. Structurally different bibenzyl derivatives were tandemly and/or divergently synthesized by co-culture engineering in various combination modes. Especially, a prenylated bibenzyl derivative ( 12) was found to be an antioxidant that exhibited potent neuroprotective activity in the cellular and rat models of ischemia stroke. RNA-seq, quantitative RT-PCR, and Western-blot analysis demonstrated that 12 could up-regulate the expression level of an apoptosis-inducing factor, mitochondria associated 3 (Aifm3), suggesting that Aifm3 might be a new target in ischemic stroke therapy. This study provides a flexible plug-and-play strategy for the easy-to-implement synthesis of structurally diverse bibenzyls through a modular co-culture engineering pipeline for drug discovery.
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【Objective】 To search compatible and suitable platelets for platelet transfusion refractoriness (PTR) patient caused by compound antibodies against HLA and CD36. 【Methods】 ELISA method was used to detect the antibody against platelet antigens and the specificity of HLA-I antibody in PTR patients. The specificity of HLA-I antibody and corresponding epitopes of patients were analyzed using MATCH IT! and HLA Matchmaker software. The HLA genotype of both donor and patient was obtained by HLA-SSO method. Compatible or suitable donor platelets for PTR patients were searched through cross-reactive group (CREG) of HLA-I and HLA epitope-matched approach (Eplet). The matching degree was identified using monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and the platelet suspension immunofluores-cence test (PIFT). Finally, the transfusion effect was evaluated according to the corrected count increment (CCI). 【Results】 Compound antibodies against both CD36 and HLA-I antigens were detected in two PTR patients, and their phenotype of CD36 was conformed to be type I deficient. Through LSA testing, high-frequency of HLA -I antibodies was found in these two patients, and the panel reactive antibody in patients 1 and 2 was 56% (54/96) and 53% (51/96), respectively. According to HLA-CREG and Eplet matching strategies, one donor of grade C-matching with patient 1 and one donor of grade D-matching with patient 2 were screened from the CD36 deficiency donor bank, respectively. And the selected donors avoided the antigen of HLA-I antibody epitope. These results of MAIPA and PIFT also confirmed that no immune response was detected between the patient and the donor. And a CCI of >4.5 within 24 hour of transfusion of compatible platelets was obtained in patient 2. 【Conclusion】 For PTR patients caused by HLA and CD36 compound antibodies, a combination strategy including serological cross-matching, HLA-CREG and Eplet approach should be used to select the CD36 deficient donor platelets which evaded the antigen corresponding to HLA-I antibodies and had the compatible HLA epitopes.
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Objective To detect the radiation of 131I in treatment site of a grade A tertiary hospital. Methods A total of 25 patients with thyroid cancer were administrated 131I at a total dose of 82880 MBq. After administration, the ambient dose equivalent rate of the ward was detected with X- and γ-ray detectors. After patient discharge, surface contamination of the ward was detected with α/β surface contamination meter. During patient hospitalization and on the day of discharge, air samples were collected from 131I treatment site and office area. The air samples were measured using a HPGe γ-ray spectrometer and the concentration of 131I in air was calculated. Results The ambient dose equivalent rate in the ward ranged from 0.15 to 0.46 μSv/h. Before ward cleaning, surface contamination ranged from 0.53 to 40.1 Bq/cm2 and the highest value was recorded on the toilet. Within 4 h after administration, the concentrations of 131I in air in treatment site and the corridor of the office area were 1.74 Bq/m3 and 0.66 Bq/m3, respectively. The ventilation air flow rate in the treatment site was 0.50 m/s. Ventilation decreased the concentration of 131I in air by 29.7%, 79.7%, and 53.3% compared with the previous day during hospitalization and on the day of discharge. Conclusion The radiation of external exposure of 131I in the treatment site is low and the shielding is effective. Before ward cleaning, the surface contamination is lower than the required limits except for the toilet. Ventilation is the primary way to reduce the concentration of 131I in air.
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【Objective】 To establish an experimental method for detecting phagocytosis of sensitized red blood cells in vitro by flow cytometry. 【Methods】 Mononuclear cells were isolated from the peripheral blood of blood donors and cultured in a cell incubator for 1 hour, and then adherent monocytes were isolated and obtained. Dib-positive red blood cells (RBCs) were labeled with PKH26 and then sensitized with IgG anti-Dib. The sensitized RBCs were added to monocytes for in vitro phagocytosis assay. Monocytes were labeled with FITC anti-human CD14, then phagocytosis was measured by flow cytometry, and the phagocytic efficiency was calculated. The method was used to detect the phagocytic efficiency of monocytes on human IgG anti-D sensitized RBCs with different titers. 【Results】 The phagocytic efficiency of monocytes was averaged at 5% (1.2%~7.6%, SD 3.30) versus 81% (71.4%~92.7%, SD 8.65) in the negative versus positive control group, respectively. Phagocytic activity of monocytes mediated by anti-D was correlated with the antibody titer. The phagocytosis efficiency was within 10% when the antibody titer was lower than 32 and increased sharply when the titer was between 32 to 128, it entered a plateau and stabilized at 80% at the titer above 256. 【Conclusion】 A detection platform for detecting phagocytosis-sensitized RBCs in vitro by flow cytometry has been successfully established. It can be used to assess the clinical significance of red blood cell allotype or autologous IgG antibodies.
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Lipid microspheres (LM) have recently been used as intravenous (i.v.) carriers for drugs, which are sufficiently soluble in oil. However, in the case of norcantharidin (NCTD), which is poorly soluble in both the water and oil phases, this approach is not feasible. In this study, NCTD-loaded LM was prepared by transferring the drug to the interfacial surface of the oil and aqueous phases to produce a less irritating i.v. formulation of NCTD. A probe type sonicator was used to disperse NCTD into the oil phase together with lecithin and Tween 80. A high-pressure homogenization process was used to prepare the lipid microspheres and localize the drug at the surfactant layer. The LM loaded with NCTD consisted of 0.02% drug. Characterization of LMs and short-term stability was performed by photon correlation spectroscopy (PCS) and a centrifugation test was also carried out. The results showed that NCTD-loaded LM (2 mg/ml) with over 80% NCTD loaded in the interfacial surface were stable for a period of 2 months, and were suitable for i.v. injection in terms of size and stability, whether be diluted or not. Such formulations produced less pain and irritation in animal studies.
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Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Química Farmacéutica/métodos , Lípidos/química , Microesferas , Animales , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacocinética , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacocinética , Glicerol/química , Concentración de Iones de Hidrógeno , Infusiones Intravenosas , Inyecciones Intramusculares , Estructura Molecular , Ácido Oléico/química , Tamaño de la Partícula , Fosfatidilcolinas/química , Polisorbatos/química , Conejos , Ratas , Ratas Wistar , Solventes/química , alfa-Tocoferol/químicaRESUMEN
In recent years, immunotherapy has become the hottest topic in the field of oncology. Both the Keynote189 study and the Keynote407 study have confirmed that progression-free survival is significantly prolonged in patients who have been benefited from immune checkpoint blockades in lung cancer. In an article published in The New England Journal of Medicine in 2012, a case report of radiation abscopal effects caused by immunization combined with conventional radiotherapy has attracted great attention in the field of oncology. The Pacific study, published in 2017, expanded the indications for immunotherapy from advanced to locally-advanced non-small cell lung cancer. The second analysis of Keynote001, published in the Lancet Oncology in the same year, suggested that radiation therapy may mediate the immune memory effects, whereas the mechanism and time window are still unclear. With the publication of PEMBRO-RT study and several pieces of work by our team in recent years, various details of radiotherapy combined with immunotherapy (iRT) have become more mature. In clinical practice, iRT is involved in the full treatment of lung cancer. However, iRT is not a hodgepodge or stew that needs further refinement and sorting. In this article, the principles, efficacy in clinical practice, and exploration of the details of iRT were discussed.
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Objective:To explore the value of matrix metalloproteinase (MMP) in differential diagnosis of brucellosis spondylitis (BS) and tuberculous spondylitis (TS).Methods:Retrospective analysis was used to collect the data of patients with BS and TS diagnosed in the First Affiliated Hospital of Xinjiang Medical University from January 2016 to December 2018. Magnetic resonance imaging (MRI), laboratory data, and the expression levels of MMP-2 and MMP-9 were analyzed.Results:There existed significant differences in imaging findings like the infection levels, the number of infected vertebrae and the paravertebral soft tissue lesions between BS and TS patients ( n=26, 27, P < 0.05). Basophils in BS patients were significantly higher than those in TS patients [(0.022±0.019) × 10 9 number/L vs (0.017±0.007) × 10 9 number/L, t=2.19, P < 0.05]; but the C-reactive protein of BS patients was significantly lower than that of TS patients [(16.12±14.16) mg/L vs (33.78±24.05) mg/L, t=2.45, P < 0.05]. The expression of MMP-9 in BS patients was significantly lower than that in TS patients [76.92% (20/26) vs 96.30% (26/27), χ 2=4.34, P < 0.05], but there was no significant difference in the expression of MMP-2 ( P > 0.05). Conclusion:MMP-9 may be a new biomarker in differential diagnosis of BS and TS, which can be helpful for the differential diagnosis of BS and TS by combining MRI findings with laboratory findings.
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Objective:To study the variation in activity in patient′s body with differentiated thyroid cancer (DTC) treated with 131I and external dose level, analyze the relationship between the both, and estimate the correction factor for the dose equivalent rate for the patients with residual activity of 400 MBq. Methods:A total of 43 DTC patients who received 131I therapy for the first time after total thyroidectomy were studied. The dose was 1 850-3 700 MBq and average dose was (2 405±777) MBq. The measurements of residual activity in patient′s body and of dose equivalent rate at 0.3, 1 and 3 m in front of the patients were performed at 2, 6, 20, 22, 24, 27, 30, 44, 46, 48, 54, 68 and 72 h after administration of 131I. Results:The residual activity in patient′s body after 131I therapy varied with time as a function of A= A0 (1.033 16e -0.062 4t+ 0.017 17). It can be estimated that the effective half-life of DTC patients treated with thyroid remnant 131I ablation therapy is 12.19 h. It needs only 26.4-38.9 h to reduce the internal activity to the 400 MBq. The functions of variation with time of normalized dose equivalent rate at 0.3, 1, and 3 m away from patients were: H· 0.3=127.220 7e -0.054 8t+ 3.765 71; H· 1=30.225 8e -0.064 4t+ 0.824 67; and H· 3=4.161 9e -0.061 5t+ 0.167 97, respectively. There was a positive correlation between residual activity and dose equivalent rate at 1 m ( r=0.982, P<0.05), and the function is H· 1=0.025 A+ 1.245. When residual activities in DTC patient′s body were 1 000, 700 and 400 MBq, the corresponding dose equivalent rates at 1 m from patients were 26.2, 18.7 and 11.2 μSv/h, respectively. The correction factors for dose equivalent rate at 0.3, 1 and 3 m from patients with 400 MBq were 0.25, 0.49 and 0.70, respectively. Conclusions:DTC patients with administration of 131I activity below 3 700 MBq need only to be hospitalized for two days to reach the discharge standards. When the residual activity in DTC patient′s body drops to 400 MBq, the dose equivalent rate at 1 m is far less than 25 μSv/h. Simply using the point source formula to estimate the dose equivalent rate around the patient will result in overestimation. Therefore, the correction factor used in the estimation of radiation doses to patients by using the formula needs to be further studied so as to make the model-based estimated result more consistent with the actual situation.
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Background@#Blackened intestines in slaughtered pigs have been commonly observed in China in recent years. However, no cause has been reported. @*Objectives@#We attempted to determine whether the blackening of the pig intestine was related to an excess of copper (Cu) in their feed. @*Methods@#In this study, we observed and collected porcine intestines in small- and large-scale pig slaughterhouses in Shandong province from May to October 2018. Twelve types of metal ions were detected in the black intestinal samples. @*Results@#The Cu level in the intestine samples was mostly higher than the Chinese national limit for food. Further study showed that Cu supplementation in most commercial porcine feed also exceeded the national standard. An animal model (mouse) that could mimic the intestinal blackening in pigs was established. Compared to control mice, Cu accumulated in the liver and intestines of mice fed an excessive Cu level, confirming the excessive Cu in the feed may be considered the major cause of blackened porcine intestines. Microscopic examination revealed that black intestines had many particles containing Cu in the lamina propria of the intestinal mucosa, and the intestinal mucosal epithelial cells showed degeneration and necrosis. @*Conclusions@#In conclusion, overuse of Cu in animal feed can lead to animal poisoning and Cu accumulation in animal products. Such overuse not only harms the health of livestock but can also affect public health.
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Background@#Blackened intestines in slaughtered pigs have been commonly observed in China in recent years. However, no cause has been reported. @*Objectives@#We attempted to determine whether the blackening of the pig intestine was related to an excess of copper (Cu) in their feed. @*Methods@#In this study, we observed and collected porcine intestines in small- and large-scale pig slaughterhouses in Shandong province from May to October 2018. Twelve types of metal ions were detected in the black intestinal samples. @*Results@#The Cu level in the intestine samples was mostly higher than the Chinese national limit for food. Further study showed that Cu supplementation in most commercial porcine feed also exceeded the national standard. An animal model (mouse) that could mimic the intestinal blackening in pigs was established. Compared to control mice, Cu accumulated in the liver and intestines of mice fed an excessive Cu level, confirming the excessive Cu in the feed may be considered the major cause of blackened porcine intestines. Microscopic examination revealed that black intestines had many particles containing Cu in the lamina propria of the intestinal mucosa, and the intestinal mucosal epithelial cells showed degeneration and necrosis. @*Conclusions@#In conclusion, overuse of Cu in animal feed can lead to animal poisoning and Cu accumulation in animal products. Such overuse not only harms the health of livestock but can also affect public health.
RESUMEN
【Objective】 To find the HLA-matched platelets from platelet donor registry and track the transfusion effect for aplastic anemia patients in pregnancy with platelet transfusion refractory (PTR) caused by anti-HLA, so as to support the childbirth and follow-up treatment of the patients. 【Methods】 Antibodies to HPA and HLA were detected by ELISA kit and Luminex, respectively. DNA of the patient and 523 platelet donors from the donor registry were extracted for high-resolution HLA genotyping. The Risk Factors Evaluation Software of PTR was used to select the ABO-compatible and HLA-matched donors, without HLA Eplets specific to the patient. After MASPAT cross matching, the patient was transfused with 1 U of platelets, and the 24h post-transfusion effect was recorded. 【Results】 Only anti-HLAⅠantibody was found in the patient serum, and the specificity Eplet was 65QIA, including HLA-B*27∶08, B*27∶05, B*07∶02, B*55∶01, B*67∶01 and B*54∶01; anti-HLA Ⅱ antibody was negative. The HLA genotypes of both the patient and donor were HLA-A*02∶07, A*11∶01, B*46∶01, B*46∶01, C*01∶02, 01∶03, DRB1*04∶05, DRB1*0901, DQB1*03∶03 and DQB1*04∶01. The results of MASPAT matching were negative. HLA-matched platelets transfusion provided a satisfactory posttransfusion platelet responses in patients(1 before vs 33 ×109/L after). A baby boy was delivered by cesarean section 4 weeks later, and the same donor was recruited due to the mother′s low Plt and bleeding trend. The 24h posttransfusion Plt (×109 / L) rose from 5 to 37 after the secondary transfusion of 1U platelet. The vital signs of the mother and her baby were normal during the two-day follow up. 【Conclusion】 The establishment of blood donor registry and screening of HLA-matched donors is an effective approach to treat PTR caused by HLA antibodies in pregnancy complicated with aplastic anemia.