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ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L-1）， Coptidis Rhizoma group（B group， 38.4 g·L-1）， processed Euodiae Fructus group（C group， 5.88 g·L-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（Cmax） of Ber， Pal， Evo， and Rut were the highest and time to peak（tmax） were the lowest in the liver of A group. In plasma， the AUC0-t and Cmax of Evo and Rut were increased in A group compared with C group， tmax of Pea was elevated and its Cmax was decreased in A group compared with D group. In the liver， compared with B-D groups， Cmax values of 5 representative components except Pae were elevated， AUC0-t of Pae was decreased and AUC0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t1/2） of each representative components in A group was elevated and tmax was decreased， and Cmax of each representative ingredient except Pal was decreased， AUC0-t values of Ber and Pal were increased， whereas the AUC0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.
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ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.
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Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.
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Germline cell gene editing is a potentially revolutionary technology that can be used to treat and prevent many genetic diseases, such as cystic fibrosis and hemophilia. Although this technology has aroused widespread discussion in the medical community and the public, its legal regulatory approach has not yet been fully determined. By summarizing and studying the experience of relevant foreign laws and regulations, this paper analyzed and summarized the current legal situation in China, and explored three ethical topics of social equality, individual subjectivity, and intergenerational rights. Combining the existing legal norms and relevant ethical considerations, the legal regulatory approach for germline cell gene editing was proposed in view of the weak operability of the law, the blurred boundaries of the legislation, and the insufficiently perfect ethical review mechanism. To better ensure that the technology can benefit mankind on the premise of eliminating risks, the following suggestions were put forward: a specialized law should be formulated based on clear legislative principles to adjust and guide the improvement of the ethical review mechanism of germline cell gene editing. It is hoped that promoting the progress of germline cell gene editing technology through in-depth research, and providing useful reference for the formulation of relevant laws and ethical policies.
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Acute myeloid leukemia (AML) is a malignant clonal proliferative disease of immature myeloid cells in hematopoietic system. Although chemotherapy and hematopoietic stem cell transplantation could improve the survival of AML patients, their prognoses are still poor. Previous studies have shown that the abnormal regulation of bone marrow microenvironment (BMM) on leukemia stem cells is one of the important factors that make AML difficult to completely cure and easy to relapse. Studies on AML molecular biology and BMM are increasing. In-depth investigation on the changes of acute leukemia microenvironment and targeted intervention of abnormal BMM are expected to make new breakthroughs in the targeted therapy of AML and to improve the prognosis of patients. This review reviews the progress of BMM and targeted microenvironment therapy in AML.
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Breast cancer， as a kind of malignant tumor with high incidence rate in female population， poses a great threat to people's health. At present， chemotherapy is the main treatment for breast cancer besides surgery and radiotherapy. However， chemotherapy is often accompanied by multidrug resistance （MDR）， which results in a series of severe consequences such as low efficacy， relapse of cancer after drug withdrawal， increased consumption of medical resources， and increased burden of medical system. Previous studies showed that the mechanism of MDR in breast cancer was quite complex， involving drug efflux， deoxyribonucleic acid （DNA） damage repair， tumor microenvironment， autophagy， epigenetic regulation， tumor stem cells， lipid metabolism， and so on. In addition， there were extensive connections among the mechanisms of MDR. Therefore， it is necessary to reveal the mechanism of MDR and develop corresponding drugs to reverse MDR， thus improving the effect of chemotherapy on treating breast cancer. Chinese medicine has the advantages of high efficiency， low toxicity， multi targets， and overall regulation. Various studies found that Chinese medicine monomer， single drug， and compound were able to reverse MDR in breast cancer by regulating the expression of drug efflux protein， promoting apoptosis， and regulating autophagy， showing the potential of anti-MDR in breast cancer. This paper summarized the research progress of the mechanism of MDR in breast cancer and the strategies of Chinese medicine in coping with MDR in breas cancer in recent years， and provided references for further research.
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Objective:To investigate the significance of Th1/Th2 cytokines in prognostic stratification of acute myeloid leukemia (AML).Methods:A total of 83 patients with newly diagnosed AML from June 2017 to April 2019 in the First People's Hospital of Yunnan Province were collected. According to the Chinese guidelines for diagnosis and treatment of adult acute myeloid leukemia (non-acute promyelocytic leukemia) (2017 edition), AML patients were divided into poor prognosis group (45 cases), moderate prognosis group (19 cases), and good prognosis group (19 cases); moderate prognosis plus poor prognosis was treated as the not good prognosis. Mann-Whitney U test and Kruskal-Wallis H test were used to compare the expression differences of Th1/Th2 cytokines in peripheral blood of different prognosis groups; cytokines with statistical differences among different prognosis groups were selected, and the cut-off value of AML patients with different prognostic stratification distinguished by cytokines was determined by using receiver operating characteristic (ROC) curve. Finally, patients were divided into ≥ cut-off value group and <cut-off value group according to the cut-off value, and then the association of both groups with the prognostic stratification in guideline was also analyzed. Results:The median expression level of tumor necrosis factor (TNF)-β of patients in moderate prognosis group [3.80 pg/ml (2.75 pg/ml, 15.32 pg/ml)] was higher than that of patients in poor prognosis group [2.78 pg/ml (1.28 pg/ml, 3.36 pg/ml)] and good prognosis group [1.61 pg/ml (0.83 pg/ml, 3.04 pg/ml)] ( U=216, P=0.02; U = 312, P < 0.05); the median expression level of TNF-β in good prognosis group was lower than that in poor prognosis group ( U = 562, P = 0.048). There were no statistically significant differences in the expression levels of Th1/Th2 cytokines of AML patients with different prognostic stratification (all P>0.05).The cut-off value of TNF-β was 3.23 pg/ml in good prognosis group and moderate prognosis group, the area under the ROC curve was 0.866 (95% CI 0.753-0.978, P < 0.05); among 26 patients with TNF-β≥ 3.23 pg/ml, 25 (96.2%) patients had not good prognosis. The cut-off value was 3.62 pg/ml for distinguishing between moderate prognosis group and poor prognosis group, the area under the ROC curve was 0.747 (95% CI 0.610-0.884, P = 0.02); 18 (100%) patients with TNF-β≥ 3.62 pg/ml had not good prognosis. The cut-off value was 2.19 pg/ml for distinguishing between good prognosis group and not good prognosis group, the area under the ROC curve was 0.719 (95% CI 0.595-0.842, P = 0.04); among 53 patients with TNF-β≥2.19 pg/ml, 46 (86.8%) patients had not good prognosis. Conclusions:The high expression of TNF-β may indicate that the prognosis of AML patients is not good. When the level of TNF-β was equal or greater than 3.62 pg/ml, it may contribute to the prognostic stratification of AML patients.
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Objective:To study the clinical prognosis and related factors affecting optimal medical therapy (OMT) compliance of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).Methods:A prospective study was conducted to select 3 818 patients who were diagnosed with CAD and successfully underwent PCI in TEDA International Cardiovascular Hospital from October 2016 to September 2017. The clinical information and application of OMT during hospitalization and 1 year later were collected for research.The patients were divided into OMT group and non OMT group according to whether they adhered to OMT during follow-up one year after discharge. After comparing the imbalance baseline data of hypertension,diabetes and hyperlipidemia with propensity score,demographic characteristics, coronary revascularization history, CAD, laboratory related laboratory examinations,and the use of OMT drugs were compared between the two groups. Cox regression model was used to analyze the relationship between long-term OMT and clinical prognosis in patients with CAD.Multivariate binary logistic regression was used to analyze the related factors affecting long-term OMT compliance.Results:A total of 3 818 cases of CAD patients were matched by propensity score and 2 596 patients were included in the study. There were 1 609 males and 987 females. The age was (62.51±9.56) years old.One year later,1298 patients (50%) insisted on OMT,including dual antiplatelet therapy(DAPT), statins, β-blockers and ACEI/ARB were 97.0% (2 517/2 596),94.5%(2 454/2 596),69.6% (1 806/2 596) and 64.2% (1 666/2 596), especially angiotensin converting enzyme inhibitors / angiotensin receptor blockers and β Receptor blockers decreased the most.Cox regression analysis showed that after adjusting for other factors, compared with non-adherence to OMT group,OMT after PCI was associated with better prognosis ( HR=0.416,95% CI 0.270-0.641, P<0.001). The prognosis of CAD patients with history of old myocardial infarction ( HR=1.804,95% CI 1.070-3.041, P=0.027),cardiac insufficiency ( HR=2.074,95% CI 1.161-3.702, P=0.014),multivessel coronary disease ( HR=2.211,95% CI 1.228-3.983, P=0.008) and BMI>24 ( HR=1.570,95% CI 1.037-2.377, P=0.033) were related to worse clinical outcomes. Multi-factor binary Logistic regression showed that OMT at hospitalization was a strong influencing factor of long-term adherence to OMT ( OR=41.278,95% CI 29.961-56.871, P<0.001). Patients with higher education,employee medical insurance and with history of PCI tend to persist in OMT. Conclusion:The medication compliance of patients with long-term OMT after PCI is still poor,while the high compliance of OMT is related to the lower incidence of adverse cardiovascular events,including death, nonfatal myocardial infarction and stroke. If there is no obvious contraindication,all patients after PCI should adhere to OMT.
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Objective:To explore the molecular mechanism of carbapenem antibiotic resistance in burns patients infected with Klebsiella pneumoniae.Methods:The patients who were diagnosed with Klebsiella pneumoniae in the burns department of Taizhou Central Hospital (Affiliated Hospital of Taizhou University) from May 2018 to October 2019 were enrolled.Ten carbapenem-resistant Klebsiella pneumoniae (CR-KP) bacterium were isolated, then the degree of resistance of CR-KP bacteria was analyzed.The common resistance genes was detected by polymerase chain reaction (PCR), the existence of resistance genes was verified through plasmid conjugation tests, and the expression of OmpK36 protein in the membrane pores was analyzed.Results:The 10 strains in this study all showed different degrees of drug resistance. The results of PCR showed that all drug resistant bacteria carried the NDM gene, and 4 strains carried the KPC gene. In addition, only a small number of resistant bacteria carried extended-spectrum β-lactamase (ESBLs) genes and AmpC genes. Plasmid conjugation experiments showed that most of the Zygomycetes were resistant to carbapenem antibiotics, and the Western blot results indicated that the protein expression of OMPK36 in the membrane pore of Zygomycetes was decreased.Conclusions:The resistance of CR-KP bacteria in burns patients was mainly caused by plasmid-mediated NDM gene insertion and reduced expression of OMPK36 protein in the membrane pore.
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Based on the rDNA sequence of Pichia pastoris, a multi-copy gene expression vector of transglutaminase (pPICZα-rDNA-mtg) was constructed and transformed to the host strain (pGAP9-pro/GS115) expressing pro peptide, to obtain the co-expression strain pro/rDNA-mtg (GS115). Real-time fluorescence quantitative PCR (qPCR) was used to analyze transglutaminase gene copy number in the 4 positive strains. We further studied the effect of gene copy on the enzyme production of recombinant Pichia pastoris as well as high-density fermentation of higher expression strain in a 3-L fermenter. The mtg copy numbers of the 4 positive strains were 2.21, 3.36, 5.72 and 7.62 (mtg-2c, mtg-3c, mtg-6c and mtg-8c), respectively, and the enzyme production capacity and protein expression level were mtg-3c>mtg-2c>mtg-6c>mtg-8c. Mtg-3c and mtg-6c of high-density fermentation had the highest enzymatic activity and enzymatic activity per unit wet weight in the supernatant of 3.12 U/mL, 52.1 U/g (wet weight) and 2.07 U/mL and 36.5 U/g (wet weight), respectively. In terms of enzyme activity per unit wet weight, mtg-3c is 1.4 times higher than that of mtg-6c. The activity of purified enzyme (mtg-3c) was up to 7.21 U/mL and the protein concentration was 437.2 μg/mL. By analyzing the effect of mtg copy number on the enzyme production of recombinant strains, mtg-3c is suitable for the co-expression of two genes (pro and mtg) in pro/rDNA-mtg, and its enzyme activity is related to higher protein secretion of the strain.
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OBJECTIVE：To analyze th e general characteristics and application of the models used in the pharmacoeconomic evaluation of type 2 diabetes mellitus （T2DM）therapy during the past 5 years，and to provide reference for the selection and improvement of T 2DM pharmacoeconomic model. METHODS ：Retrieved from PubMed ，Embase，CNKI，Wanfang database and VIP during Jan. 1st，2015 to Dec. 31st，2019，pharmacoeconomic evaluation literatures about T 2DM therapy were collected ；the included model was analyzed in respects of general structure ，therapy plan establishment ， short-term therapeutic efficacy ， complication simulation ，model effectiveness validation ，application frequency. RESULTS ：A total of 81 literatures were included ， involving 14 models，such as CORE model ，Cardiff model ，ECHO model ，etc. Mostly ，Markov or micro Markov simulation method were adopted to measure the patient ’s lifetime health outcome and cost mostly from the point of view of third-party payer. Seven models could simulate 2-4 therapy plans ；short-term efficacy mainly included risk factors of diabetic complications （such as glycosylated hemoglobin level and body mass ）and adverse drug reactions. Most models used intermediate indexes to simulate the occurrence of complications ，and the number of complications ranged from 3 to 15；the validity of model effectiveness included surface validity ，internal validity and external validity ，etc. Among 14 models，the most frequently used models in the past 5 years were long-term models that had been validated ，among which CORE model had the most application times （38/81，46.91％）， followed by Cardiff model （12/81，14.81％）. CONCLUSIONS ：The 14 models have similar structure. The differences of the models are mainly reflected in 3 aspects as therapy plan setting， considered short-term efficacy ， the number of model are ideally choose based on available evidences.
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Objective:To investigate the expression of epigenetic inhibitor polycomb group proteins such as enhancer of zeste homolog 1/2 (EZH1/EZH2), embryonic ectoderm development protein (EED) and suppressor of zeste 12 (SUZ12) in common cutaneous T-cell lymphomas and lymphoproliferative disorders (CTCL/LPD) .Methods:Totally, 93 paraffin-embedded skin samples of CTCL/LPD and 8 of lichen planus were collected from Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College between 2012 and 2019, and subjected to immunohistochemical staining to determine the protein expression of EZH2, EED, SUZ12 and EZH1. Statistical analysis was carried out with SPSS 25.0 software by using chi-square test and Spearman correlation analysis.Results:The 93 cases of CTCL/LPD included 44 cases of mycosis fungoides (MF), 17 natural killer/T cell lymphoma (NK/TCL), 8 primary cutaneous anaplastic large cell lymphoma (PC-ALCL), 8 lymphomatoid papulosis (LyP), 8 hydroa vacciniforme-like lymphoproliferative disorder (HV-like LPD) and 8 cases of subcutaneous panniculitis-like T cell lymphoma (SPTCL). Among the 93 CTCL/LPD cases, 83 (89.2%) were positive for EZH2, 81 (87.1%) for EED, 78 (83.9%) for SUZ12 and 37 (39.8%) for EZH1; among the 8 cases of lichen planus, 1 was positive for EZH2, all were positive for EZH1, and all were negative for EED and SUZ12. The expression of EZH2, EED, SUZ12 and EZH1 in lichen planus samples significantly differed from all the CTCL/LPD samples ( χ2 = 41.75, 39.74, 39.36, 32.83, respectively, all P < 0.001), and from MF, NK/TCL, PC-ALCL, LyP, HV-like LPD and SPTCL samples separately (α = 0.008 3, all P < 0.001). Meanwhile, the score of EZH2 expression was negatively correlated with that of EZH1 expression in the MF, NK/TCL, PC-ALCL, LyP, HV-like LPD and SPTCL tissues ( rs = -0.60, -0.68, -0.89, -0.74, -0.93, -0.80, respectively, all P < 0.05) . Conclusion:Polycomb group proteins EZH2, EED, SUZ12 and EZH1 are abnormally expressed in CTCL/LPD lesions.
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Objective:To verify the ability of the newly developed ultra-high resolution CT (U-HRCT) for displaying the fine bony anatomy of temporal bone.Methods:The cone-beam CT architecture was used on U-HRCT. The focus size of X-ray generator was 0.27 mm × 0.29 mm, the rated tube voltage was 60-100 kV, and the unit size of flat panel detector was 0.074 8 mm×0.074 8 mm. From October to December 2019, 16 adult head specimens (32 temporal bones, provided by Huanghe University of Science and Technology) were imaged using U-HRCT. The scanning mode was small-field-of-view and high-resolution scanning for unilateral temporal bone. The scanning parameters were: voltage 100 kV, current 3.5 mA, rotation time 40 s, reconstructed field of view 65 mm×65 mm, voxel size 0.1 mm×0.1 mm×0.1 mm, layer number 370, slice thickness 0.1 mm, and slice interval 0.1 mm. The ultimate spatial resolution of the system was detected using a phantom with line pair card, after the scanning with the same parameters. Through multi-planar reconstruction and minimum intensity projection method, a total of 6 anatomical positions of 4 structures (stapes footplate, cochlear axis bottom, vestibular aqueduct internal orifice and isthmus, cochlear aqueduct internal orifice and auditory sac segment) were scored with 1-3 points. The Wilcoxon test was used to compare the difference of bilateral scores of each structure.Results:The phantom test results showed that the ultimate spatial resolution of the system was ≥4.0 lp/mm. The scores of stapes footplate, cochlear axis bottom and vestibular aqueduct internal orifice were ≥2 points, with a display rate of 100%. The display rates of vestibular aqueduct isthmus, cochlear aqueduct internal orifice and auditory sac segment were 87.5% (28/32), 71.9% (23/32) and 53.1% (17/32), respectively. There were no significant differences in left and right scores of all anatomical structures ( P>0.05). Conclusion:The newly developed U-HRCT has good display ability for fine bony anatomy of temporal bone and has great clinical application potential.
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Objective:To investigate the levels of trace elements(iron, zinc, magnesium and copper) in 0~9 years old children in Shenyang, and to explore the relationship between trace elements and humoral immunity(IgA, IgG and IgM).Methods:From September 2018 to October 2019, retrospective analysis was performed in children aged 0-9 who admitted to the Fourth Hospital Affiliated to China Medical University and underwent trace elements and humoral immunity(IgA, IgG and IgM).Results:A total of 422 children met the criteria, including 228 boys and 194 girls.The rates of iron deficiency in children aged 0-3, 4-6 and 7-9 were 17.5%, 18.2% and 14.0%, respectively, and zinc deficiency rates were 10.0%, 9.0% and 10.5%, respectively.There were no statistically significant differences in the rates of iron deficiency and zinc deficiency in each age group(χ 2=0.520, P>0.05; χ 2=0.135, P>0.05). Magnesium and copper levels in all children were in the normal range.The levels of IgA and IgG [(1.24±0.77)g/L, (9.07±3.04)g/L] in the zinc deficiency group were significantly lower than those in the normal group [(0.94±0.55)g/L, (8.18±2.11)g/L], the differences were statistically significant( t=-2.858, -2.440, all P<0.05), while there was no statistically significant difference in IgM level between the two groups( t=-0.870, P>0.05). There were no statistically significant differences in IgA, IgG and IgM levels between the iron deficiency group and the iron normal group( t=-1.346, -0.960, 0.029, all P>0.05). There was a significant positive correlation between zinc level and IgA, IgG levels( r=0.184, 0.142, all P<0.05), but there was no significant correlation with IgM( r=0.08, P>0.05). Iron, copper and magnesium levels were not significantly correlated with IgA, IgG and IgM levels( P>0.05). Conclusion:Deficiency of zinc can cause reduction of IgA and IgG, which may be related to repeated infection in children.
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Triple negative breast cancer (TNBC) is associated with a high risk of recurrence and generally a poor prognosis. Median survival time of metastatic triple negative breast cancer (mTNBC) is about one year. Currently, the mainstay of treatment for mTNBC remains cytotoxic chemotherapy. In recent years, the drugs involved in the clinical researches of mTNBC include poly-ADP-ribose polymerase inhibitors, phosphoinositide 3-kinase pathway inhibitors, antibody targeting epidermal growth factor receptor, antibody targeting trophoblast surface antigen-2, antibody targeting death receptor 5, endocrine therapy drugs for androgen receptor, and immune checkpoint inhibitors and so on. New drugs have gradually improved the survival of patients with mTNBC.
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The intestinal flora in patients with leukemia is significantly different from healthy people. Some studies have found that intestinal flora can participate in leukemia progression by regulating the body's immune system and hematopoietic system and affecting the metabolic function, but the underlying molecular mechanism is not clear. Maintaining the intestinal microecological balance and exploring intestinal microbes that can be used as therapeutic targets have a profound significance for prolonging the survival of leukemia patients.
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At present, the treatment methods of lymphoma mainly include the combined chemotherapy, hematopoietic stem cell transplantation, immunotherapy and new targeted therapies, but the treatment-related drug resistance, recurrence, extranodal and central nervous system infiltration, and leukemia transformation are still intractable problems that need to be solved in clinical practice. Studies have shown that cytokines are expressed to varying degrees in patients with lymphoma, which are significantly related to the progression of lymphoma, poor prognosis, chemotherapy response, and drug resistance. It has been confirmed that interleukin 6 (IL-6) and IL-10 are highly expressed in all types of lymphoma, and IL-10 is highly expressed in the cerebrospinal fluid of central nervous system lymphoma, all of which indicate a poor prognosis. This article reviews the role of cytokines in the development, treatment and prognosis of lymphoma.
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Objective@#To investigate the expression of LC3B, p-AMPKα and p27 in cortical tuberous sclerosis complex (TSC).@*Methods@#Nineteen specimens of surgically resected TSC cortical tubers were collected at Xuanwu Hospital, Capital Medical University, from 2014 to 2017. The expression of the three proteins in the lesions and the adjacent relatively normal regions was detected by immunohistochemical staining (EnVision two-step method).@*Results@#LC3B was mainly expressed in the dysmorphic neuron and giant cell in TSC cortical tubers and in the adjacent relatively normal neurons, and the expression was diffuse or perinuclear cytoplasmic. There was no significant difference in the average optical density between abnormal cells and neurons adjacent to the lesions (0.343±0.195 vs. 0.419±0.088, P>0.05). p-AMPKα was localized in the cytoplasm of dysmorphic neurons and giant cell in TSC cortical tubers. The average optical density of abnormal cells in the lesions was significantly higher than that of neurons adjacent to the lesions (0.306±0.123 vs. 0.233±0.654, P<0.05). P27 showed nuclear positivity, mainly expressed in the neurons and glial cells close to TSC cortical tubers, while the positive rate in the abnormal cells in TSC cortical tubers was low (15/19 vs. 7/19, P<0.05).@*Conclusion@#There is no significant decrease in the level of autophagy in dysmorphic neurons and giant cells in TSC cortical tubers, which may be related to the compensatory mechanism of AMPK signaling pathway, but without activation of downstream p27.
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Objective To study the detection rate of pathogens from sputum , blood, and bronchoalveolar lavage fluid ( BALF ) samples in acquired immunodeficiency syndrome ( AIDS ) patients complicated with pulmonary infection.Methods Seventy-three hospitalized AIDS patients complicated with pulmonary infection in Beijing Ditan Hospital , Capital Medical University were enrolled from February 2018 to September 2018.Blood, sputum and BALF samples were collected.Blood samples were cultured to detect anaerobic bacteria, aerobic bacteria, fungi and mycobacteria.Antigen agglutination method was applied in blood samples to detect cryptococcus neoformans.The sputum samples were tested for Mycobacterium tuberculosis by acid-fast staining and were cultured to detect bacteria and fungi.The sputum samples were observed under microscope for sporotrichosis and fungal spores.The BALF samples were cultured to detect bacteria and fungi. The BALF samples were tested for Mycobacterium tuberculosis by polymerase chain reaction amplification and acid-fast staining.Pneumocystis were detected in BALF samples by methenamine silver staining method .The BALF samples were observed under a microscope for sporotrichosis and fungal spores .The detection rate of pathogens from blood, sputum and BALF samples were compared.Chi-square test was conducted for statistical analysis.Results In 73 AIDS patients complicated with pulmonary infection , the pathogen detection rates in blood, sputum and BALF samples were 8 (11.0%), 23 ( 31.5%) and 48 (65.8%), respectively.The difference was statistically significant ( F ＝48.513, P ＜0.01 ).The detection rate in BALF samples was significantly higher than that in blood or sputum samples ( χ2 ＝43.349 and 17.136, respectively, both P＜0.01).The detection rate in sputum samples was significantly higher than that in blood (χ2 ＝9.215, P＜0.05). The highest detection rates of pathogens in blood , sputum and BALF samples were Talaromyces marneffei 4.1%(3), viridans group streptococci 16.4%(12) and 35.6%(26), respectively.Conclusions The detection rate of pathogens in BALF samples from AIDS patients complicated with pulmonary infection is the highest , followed by sputum and blood samples.
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Objective: To investigate the application of single-molecule PCR (SM-PCR) in the detection of plasma ctDNA for the treat-ment of patients with advanced lung adenocarcinoma. Methods: In total, 30 patients diagnosed with advanced lung adenocarcinoma were enrolled between June 2017 and May 2018. ctDNA fragments of the target genes (EGFR, KRAS, BRAF, ALK, HER2, and TP53) from the blood samples were enriched by SM-PCR, and DNA libraries were prepared. Finally, a high-throughput sequencing was performed. The EGFR detection of tumor tissue samples was performed using real-time fluorescence PCR based on the amplification refractory mutation system (ARMS) and consistency in the results of EGFR mutation detection in the plasma and tissue was compared. Results:The results of both the methods were consistent (Kappa=0.867, P<0.001). The McNemar's test also indicated that the results are not statistically different (P=0.500). Conclusions: SM-PCR can be used for the detection of plasma EGFR mutations. The target detection sites are more comprehensive and multiple mutations can be detected at the same time. Results of the analysis are more precise and can be absolutely quantified.