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This study aimed to investigate the role of macrophage polarization in the treatment of liver fibrosis by Fuzheng Huayu Tablets(FZHY) through single-cell, transcriptome sequencing and in vitro and in vivo experiments. Liver fibrosis-related datasets, transcriptomic datasets, and single-cell sequencing datasets were obtained from the Gene Expression Omnibus(GEO) database to screen differential genes. Liver fibrosis-related genes were obtained from GeneCards, DisGeNET, NCBI, PharmgKB, TTD and OMIM databases. Macrophage polarization-related genes were obtained from the GeneCards database. The above three gene sets were intersected to construct a protein-protein interaction(PPI) network. Cytoscape software was used to screen core proteins, and the expression pattern of core proteins was visualized by single-cell sequencing. A mouse model of liver fibrosis was constructed using carbon tetrachloride(CCl_4). Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of liver tissues. The expressions of α-smooth muscle actin(α-SMA) and transforming growth factor-ß1(TGF-ß1) were detected by immunohistochemistry. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by colorimetry. The le-vels of inflammatory factors in serum were detected by the enzyme-linked immunosorbent assay(ELISA). Furthermore, the expressions of α-SMA, TGF-ß1, cluster of differentiation 86(CD86) and thrombospondin 1(THBS1) in liver tissues were detected by Western blot(WB). Lipopolysaccharide(LPS) was used to stimulate RAW264.7 cells to construct the M1 macrophage polarization model. The cell counting kit-8(CCK-8) method was used to detect cell viability. WB was used to detect the protein expressions of CD86 and THBS1 in cells, and the messenger ribonucleic acid(mRNA) expression levels of tumor necrosis factor-α(TNF-α) and interleukin(IL)-1ß by real-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-qPCR). The results showed that a total of 26 potential genes related to the polarization of liver fibrosis macrophages were obtained, and 10 core proteins related to the polarization of liver fibrosis macrophages such as THBS1, lumican(LUM) and fibulin-5(FBLN5) were screened. Single-cell data analysis indicated that THBS1, ranking highest, may be expressed by M1 macrophages. Animal experiments demonstrated that FZHY reduced inflammatory cell infiltration and collagen deposition in CCl_4-induced mouse liver, relieved liver injury and inflammation levels, and inhibited the expressions of α-SMA, TGF-ß1, CD86, and THBS1 proteins. Cell experiments revealed that FZHY significantly reduced intracellular expression of CD86 and THBS1 proteins and mRNA levels of TNF-α and IL-1ß. In conclusion, FZHY may ameliorate liver fibrosis by inhibiting THBS1 protein expression, suppressing M1 macrophage polarization, and reducing inflammation.
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Medicamentos de Ervas Chinesas , Cirrose Hepática , Transcriptoma , Animais , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Transcriptoma/efeitos dos fármacos , Masculino , Análise de Célula Única , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Single nucleotide polymorphisms (SNPs) play a fundamental role in human genetic variation and are used in medical diagnostics, phylogeny construction, and drug design. They provide the highest-resolution genetic fingerprint for identifying disease associations and human features. Haplotypes are regions of linked genetic variants that are closely spaced on the genome and tend to be inherited together. Genetics research has revealed SNPs within certain haplotype blocks that introduce few distinct common haplotypes into most of the population. Haplotype block structures are used in association-based methods to map disease genes. In this paper, we propose an efficient algorithm for identifying haplotype blocks in the genome. In chromosomal haplotype data retrieved from the HapMap project website, the proposed algorithm identified longer haplotype blocks than an existing algorithm. To enhance its performance, we extended the proposed algorithm into a parallel algorithm that copies data in parallel via the Hadoop MapReduce framework. The proposed MapReduce-paralleled combinatorial algorithm performed well on real-world data obtained from the HapMap dataset; the improvement in computational efficiency was proportional to the number of processors used.
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Algoritmos , Biologia Computacional , Genoma Humano , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Endosymbiosis with chemosynthetic Gammaproteobacteria is widely recognized as an adaptive mechanism of siboglinid tubeworms, yet evolution of these endosymbionts and their driving forces remain elusive. Here, we report a finished endosymbiont genome (HMS1) of the cold-seep tubeworm Sclerolinum annulatum. The HMS1 genome is small in size, with abundant prophages and transposable elements but lacking gene sets coding for denitrification, hydrogen oxidization, oxidative phosphorylation, vitamin biosynthesis, cell pH and/or sodium homeostasis, environmental sensing, and motility, indicative of early genome erosion and adaptive evolution toward obligate endosymbiosis. Unexpectedly, a prophage embedded in the HMS1 genome undergoes lytic cycle. Highly expressed ROS scavenger and LexA repressor genes indicate that the tubeworm host likely activates the lysogenic phage into lytic cycle through the SOS response to regulate endosymbiont population and harvest nutrients. Our findings indicate progressive evolution of Sclerolinum endosymbionts toward obligate endosymbiosis and expand the knowledge about phage-symbiont-host interaction in deep-sea tubeworms.
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Sponges are widely distributed in the global ocean and harbor diverse symbiotic microbes with mutualistic relationships. However, sponge symbionts in the deep sea remain poorly studied at the genome level. Here, we report a new glass sponge species of the genus Bathydorus and provide a genome-centric view of its microbiome. We obtained 14 high-quality prokaryotic metagenome-assembled genomes (MAGs) affiliated with the phyla Nitrososphaerota, Pseudomonadota, Nitrospirota, Bdellovibrionota, SAR324, Bacteroidota, and Patescibacteria. In total, 13 of these MAGs probably represent new species, suggesting the high novelty of the deep-sea glass sponge microbiome. An ammonia-oxidizing Nitrososphaerota MAG B01, which accounted for up to 70% of the metagenome reads, dominated the sponge microbiomes. The B01 genome had a highly complex CRISPR array, which likely represents an advantageous evolution toward a symbiotic lifestyle and forceful ability to defend against phages. A sulfur-oxidizing Gammaproteobacteria species was the second most dominant symbiont, and a nitrite-oxidizing Nitrospirota species could also be detected, but with lower relative abundance. Bdellovibrio species represented by two MAGs, B11 and B12, were first reported as potential predatory symbionts in deep-sea glass sponges and have undergone dramatic genome reduction. Comprehensive functional analysis indicated that most of the sponge symbionts encoded CRISPR-Cas systems and eukaryotic-like proteins for symbiotic interactions with the host. Metabolic reconstruction further illustrated their essential roles in carbon, nitrogen, and sulfur cycles. In addition, diverse putative phages were identified from the sponge metagenomes. Our study expands the knowledge of microbial diversity, evolutionary adaption, and metabolic complementarity in deep-sea glass sponges.
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The deep-sea hydrothermal vents (DSHVs) in the Southwest Indian Ridge (SWIR) are formed by specific geological settings. However, the community structure and ecological function of the microbial inhabitants on the sulfide chimneys of active hydrothermal vents remain largely unknown. In this study, our analyses of 16S rRNA gene amplicons and 16S rRNA metagenomic reads showed the dominance of sulfur-oxidizing Ectothiorhodospiraceae, Thiomicrorhabdus, Sulfurimonas, and Sulfurovum on the wall of two active hydrothermal chimneys. Compared with the inactive hydrothermal sediments of SWIR, the active hydrothermal chimneys lacked sulfur-reducing bacteria. The metabolic potentials of the retrieved 82 metagenome-assembled genomes (MAGs) suggest that sulfur oxidation might be conducted by Thiohalomonadales (classified as Ectothiorhodospiraceae based on 16S rRNA gene amplicons), Sulfurovaceae, Hyphomicrobiaceae, Thiotrichaceae, Thiomicrospiraceae, and Rhodobacteraceae. For CO2 fixation, the Calvin-Benson-Bassham and reductive TCA pathways were employed by these bacteria. In Thiohalomonadales MAGs, we revealed putative phytochrome, carotenoid precursor, and squalene synthesis pathways, indicating a possible capacity of Thiohalomonadales in adaptation to dynamics redox conditions and the utilization of red light from the hot hydrothermal chimneys for photolithotrophic growth. This study, therefore, reveals unique microbiomes and their genomic features in the active hydrothermal chimneys of SWIR, which casts light on ecosystem establishment and development in hydrothermal fields and the deep biosphere.
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Objective To compare the clinical efficacy of anti-vascular endothelial growth factor(VEGF)combined with pars plana vitrectomy(PPV)treatment for patients with proliferative diabetic retinopathy(PDR)of different traditional Chinese medicine(TCM)syndrome types in the real world.Methods A prospective real-world study was performed in the 36 patients(involving 42 eyes)with PDR treated by anti-VEGF combined with PPV in the Department of Ophthalmology of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from March 2019 to December 2019.According to the TCM syndrome manifestations,the patients were differentiated as qi-yin deficiency complicated with blood stasis obstructing collaterals type(15 cases,involving 18 eyes;shorten as qi-yin deficiency type),liver-kidney deficiency and ocular collaterals failing in the nourishment type(14 cases,involving 17 eyes;shorten as liver-kidney deficiency type),and yin-yang deficiency complicated with blood stasis and phlegm coagulation type(7 cases,involving 7 eyes;shorten as yin-yang deficiency type).The patients were treated with anti-VEGF therapy first and then received PPV after 5-7 days.Aqueous humor was sampled during anti-VEGF therapy and PPV.After treatment,the efficacy of PDR patients with different TCM syndromes was compared.Moreover,the patients were observed in the best corrected visual acuity(BCVA)of the affected eyes before surgery and 3 months after surgery,levels of cytokines in the aqueous humor before and after anti-VEGF treatment,macular central retinal thickness(CRT),area of the foveal avascular zone(FAZ),the blood density of macular center,inner ring,outer ring and intact macula 3 months after surgery,and the postoperative complications.Results(1)The difference of the therapeutic efficacy of PDR patients with various TCM syndrome types was statistically significant(P<0.05).Among 3 syndrome types,the best efficacy was found in the qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type,with the total efficacy rate being 88.89%(16/18),52.94%(9/17),and 42.86%(3/7),respectively.(2)Three months after surgery,the logarithmic value of minimum angle of resolution(LogMAR)for BCVA of patients with qi-yin deficiency type was significantly superior to that of patients with yin-yang deficiency type,with the difference being statistically significant(P<0.05).After the anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients varied in the 3 syndrome types:vascular endothelial growth factor A(VEGF-A)level in the patients with the 3 syndrome types was significantly lower,placental growth factor(PLGF)and angiopoietin-like protein 4(ANGPTL4)levels in the patients with qi-yin deficiency type were higher,and interleukin 8(IL-8)level in the patients with liver-kidney deficiency type was higher than those before treatment,and the differences were statistically significant(P<0.05 or P<0.01).The blood density of macular outer ring and intact macula in the patients with qi-yin deficiency type and liver-kidney deficiency type was larger than that in the patients with yin-yang deficiency type,and the differences were statistically significant(P<0.05).However,the differences of CRT,FAZ area,and blood density of macular center and inner ring among the 3 syndrome types were not statistically significant(P>0.05).(3)The incidence of postoperative complications in the patients with yin-yang deficiency type was relatively high,but the difference among the 3 syndrome types was not statistically significant(P>0.05).Conclusion In the real world,the best efficacy of anti-VEGF combined with PPV treatment in PDR patients with different TCM syndrome types can be achieved in the patients differentiated as qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type.After anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients vary in the 3 syndrome types.Three months after the operation,the patients with qi-yin deficiency type and liver-kidney deficiency type have larger blood density of macular outer ring and intact macula,and exert good prognosis.
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Objective:To survey and analyze the current status and needs of health management for hypertension in empty-nest elderly.Methods:In this cross-sectional study, 677 cases of empty-nest elderly with hypertension who underwent health checkups at the Health Management Center of Sichuan Provincial People′s Hospital from March 1st to June 30th, 2022 were selected consecutively by convenience sampling method to conduct a questionnaire survey. The questionnaires included general demographic information, and the current status and needs of health management for hypertension. A total of 677 questionnaires were distributed, and all the questionnaires were recalled, of which 675 (99.7%) were valid. According to the Classification and Definition of Blood Pressure Levels in the Guidelines for Primary Care of Hypertension (2019) the elderly with mean systolic blood pressure controlled between 90 and 139 mmHg (1 mmHg=0.133 kPa) and mean diastolic blood pressure controlled between 60 and 89 mmHg were set as normal blood pressure group (257 cases), and the ones with mean systolic blood pressure ≥140 mmHg and/or mean diastolic blood pressure ≥90 mmHg were set as abnormal blood pressure group (418 cases). The current management status and needs of hypertension between the two groups was compared, and the χ2 test and multi-factor logistic regression were used to analyze the factors influencing the health management level of hypertension among empty-nest elderly. Results:Most of the empty-nest elderly had their blood pressure monitored once a week (40.30%), most of them had their blood pressure reviewed in outpatient setting for no more than one time per year (40.89%), their blood pressure was mainly controlled by medication (48.30%), more than half of them took medication very regularly (51.84%), and the proportion of the elderly with abnormal blood pressure was much higher than that of those with normal blood pressure (61.93% vs 38.07%). Compared with living with or nearby their children, empty-nest elderly preferred to live alone or with their spouses (63.11% vs 15.85% and 21.04%), and the proportion of those who wanted to be taken care of by their children was much lower than those who wanted to be taken care of by the community and mutual care among the elderly (7.70% vs 58.07% and 34.22%); and the people they wanted to talk to were mainly their children (53.19%). In terms of community services, the needs for medical services in empty-nest elderly was higher than the needs for old-age security and cultural entertainment (43.11% vs 36.15% and 20.74%), and the needs for community medical services was focused on blood pressure measurement (89.04%). The proportions of education level of college and above, high household income, regular medication taking, daily blood pressure monitoring, and desire for frequent child care were significantly lower in the abnormal blood pressure group than those in the normal blood pressure group (34.91% vs 58.35%, 5.17% vs 24.16%, 34.89% vs 63.72%, 28.47% vs 44.75%, and 3.35% vs 10.12%), and the proportion without medical insurance was significantly higher than that in the normotensive group (8.13% vs 3.11%) (all P<0.05). The presence of medical insurance (employee medical insurance, OR=1.986, 95% CI: 1.130-3.492; resident medical insurance, OR=1.291, 95% CI: 1.044-1.598) was positively associated with the health management level of hypertension among empty-nest elderly, while low frequency of blood pressure monitoring (once a week, OR=0.243, 95% CI: 0.101-0.583;≤once a month, OR=0.210, 95% CI: 0.067-0.661) and irregular medication taking (occasionally forget, OR=0.430, 95% CI: 0.186-0.996; often forget, OR=0.361, 95% CI: 0.147-0.886) were negatively associated with the health management level of hypertension among empty-nest elderly (all P<0.05). Conclusions:The health management level of hypertension in empty-nest elderly needs to be improved. Community care, medical services and communication with children are the main needs in the empty-nest elderly. The type of medical insurance, frequency of blood pressure monitoring and medication-taking status are correlated with the hypertension management level in empty-nest elderly.
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AIM AND OBJECTIVE: In the past decade, the drug design technologies have been improved enormously. The computer-aided drug design (CADD) has played an important role in analysis and prediction in drug development, which makes the procedure more economical and efficient. However, computation with big data, such as ZINC containing more than 60 million compounds data and GDB-13 with more than 930 million small molecules, is a noticeable issue of time-consuming problem. Therefore, we propose a novel heterogeneous high performance computing method, named as Hadoop-MCC, integrating Hadoop and GPU, to copy with big chemical structure data efficiently. MATERIALS AND METHODS: Hadoop-MCC gains the high availability and fault tolerance from Hadoop, as Hadoop is used to scatter input data to GPU devices and gather the results from GPU devices. Hadoop framework adopts mapper/reducer computation model. In the proposed method, mappers response for fetching SMILES data segments and perform LINGO method on GPU, then reducers collect all comparison results produced by mappers. Due to the high availability of Hadoop, all of LINGO computational jobs on mappers can be completed, even if some of the mappers encounter problems. RESULTS: A comparison of LINGO is performed on each the GPU device in parallel. According to the experimental results, the proposed method on multiple GPU devices can achieve better computational performance than the CUDA-MCC on a single GPU device. CONCLUSION: Hadoop-MCC is able to achieve scalability, high availability, and fault tolerance granted by Hadoop, and high performance as well by integrating computational power of both of Hadoop and GPU. It has been shown that using the heterogeneous architecture as Hadoop-MCC effectively can enhance better computational performance than on a single GPU device.
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Algoritmos , Desenho Assistido por Computador , Metodologias Computacionais , Desenho de Fármacos , Big Data , Estrutura Molecular , Relação Quantitativa Estrutura-AtividadeRESUMO
Objective: To understand the epidemiological characteristics of tick-borne infectious diseases (TBID) and the risk factors of severe illness and death in Hubei Province from 2016 to 2021. Methods: Based on the incidence data of fever with thrombocytopenia syndrome (SFTS), tsutsugamushi disease, typhus and other TBID reported during 2016-2021, the epidemiological analysis was conducted. Field investigation results of TBID in areas with high incidence in 2021, logistic regression analysis of population characteristics, epidemiological history and other factors were used to explore the risk factors of severe and fatal cases. In the field vector investigation, free ticks and surface ticks of the host animals in the cases' home and surrounding grassland were monitored and detected. Results: A total of 3 826 TBID cases were reported in Hubei from 2016 to 2021, of which 71.30% (2 728/3 826) were SFTS, 13.04% (499/3 826) were tsutsugamushi disease and 15.66% (599/3 826) were typhus. A total of 44 cases died in 6 years; the fatality rate was 1.15% (44/3 826). In the peak seasons of incidence from May to July, the cases in people engaged in agriculture related work accounted for 84.61% (3 237/3 826). The incidence rate in women was higher than that in men, and the cases aged ≥50 years accounted for 81.02% of the total (3 100/3 826), and the incidence rate increased with age (P<0.001). The TBID cases were distributed in 86 counties and districts in 16 prefectures (municipality). The incidence rates of different areas had significant differences (P<0.05), and there was a certain spatial-temporal clustering and expasion. Bovis microplus and Haemaphysalis longicornis were captured in the field, and the positive rates in host animals and grassland ticks were 10.94% (7/64) and 40.00% (2/5), respectively. Univariate logistic regression analysis results showed that age ≥50 years and leukocyte <2.0×109/L were risk factors for severe illness and death. Conclusions: The TBID reported in Hubei were mainly SFTS, tsutsugamushi disease and typhus. In order to reduce the incidence of TBID, it is necessary to strengthen the prevention and control in women aged ≥50 years and reduce field exposure and tick bites during the epidemic period.
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Animais , Feminino , Tifo Epidêmico Transmitido por Piolhos , Tifo por Ácaros/epidemiologia , Febre Grave com Síndrome de Trombocitopenia , Carrapatos , Doenças Transmissíveis , Phlebovirus , China/epidemiologia , Doenças Transmitidas por Carrapatos/epidemiologiaRESUMO
AIM: To optimize the technique of intravenous injection of Evans blue and retinal preparations in mice, improving the accuracy and repeatability of staining experiment of retinal preparations.METHODS: C57BL/6 male mice were intravenous injected with 10g/L(1%)Evans Blue 0.3mL and circulated in vivo for 10 or 20min, and the eyes were removed after sacrificed and fixed in 4% paraformaldehyde for 20, 40 or 60min. When failure of intravenous injection, the experiment was remediated by intraperitoneal injection of 1% Evans Blue 0.3mL, circulated in vivo for 3h and fixed for 60min to observe morphology, distribution and leakage of the retinal vessels. Besides, we compared the morphology, distribution and leakage of the retinal vessels after intravenous injection with those after intraperitoneal injection to determine the optimal conditions for in vivo circulation time and retinal preparations.RESULTS: After intravenous injection, compared to the retinal vascular condition under 20min in vivo circulation time of Evans blue and 20 or 40min of fixation, with 10min of in vivo Evans blue circulation and 60min of fixation, the morphology of retinal vascular was more intact with less retinal vascular leakage, and the vascular branches are clear. When intravenous injection failed, remediated results from intraperitoneal injection showed that the morphology and distribution of retinal vessels were intact. There was no significant difference in morphology, distribution and leakage of the retinal vessels after 3h of intraperitoneal Evans blue circulation compared to 10min intravenous Evans blue circulation.CONCLUSION: This experiment optimizes the protocol, improves the accuracy and reproducibility of retinal preparations, and provides a reference for the study of related retinal vascular diseases.
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Objective@#To explore the effect of C1q / tumor necrosis factor-related protein 9 ( CTRP9 ) on the expression of genes and proteins related to lipid metabolism of brown adipose tissue (BAT) in mice after cold stimulation.@*Methods @#C57BL /6J male mice were injected with adenovirus Ad-GFP (control group) or Ad-CTRP9 ( experience group) into the scapular region and kept for 7 days.After cold stimulation at 4 ℃ for 10 hours,the expression levels of BAT marker genes and proteins were detected by real time PCR and Western blot. @*Results@#Overexpression of CTRP9 induced by cold stimulation significantly increased the mRNA level of iodothyronine deiodinase 2 (Dio2) in BAT (P<0. 01) .Additionally,there was no significant difference in the expression of BAT marker genes ( UCP-1,PGC-1 α , PRDM16 and ARβ3) ,and liposynthesis and lipolysis related genes (PPARγ , HSL and ATGL) .Uncoupling protein 1 (UCP-1) protein expression was upregualted in Ad-CTRP9 compared to the Ad-GFP control group ,while the expression of lipolysis related protein adipose triglyceride lipase ( ATGL) decreased significantly (P<0. 05) .@*Conclusion@#In cold environment,overexpression of CTRP9 promotes the accumulation of UCP-1 protein in BAT,upregulates the expression of thyroid hormone signal related gene Dio2,and inhibits triglyceride hydrolysis to maintain a constant body temperature.
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Objective:To systematically evaluate the psychological experience of unmarried women after artificial abortion by Meta integration method.Methods:A literature search was conducted from PubMed, Web of Science, EMbase, Medline, CNKI, WanFang, VIP, CBM databases with the combination of subject words and free words. The Chinese and English search terms included “unmarried women” “abortion” “pregnancy termination” “perception” “qualitative research”, etc; the researched time was from the establishment of the database to April 26, 2022. The literature was evaluated according to the quality evaluation standard of JBI Evidence-based Health Care Center, and then the results where integrated.Results:A total of 8 articles were included, including two Chinese articles and the six English articles, all of which were classified as B grade, with 28 complete results extracted, and the similar results were integrated into 8 categories, finally 4 synthesis results were synthesized: (1) lack of relevant knowledge; (2) be overburdened; (3) a desire to be supported and cared; (4) seek relevant knowledge, organization help and active response.Conclusion:The general psychological experience of unmarried women after artificial abortion is poor, lack of relevant knowledge, heavy psychological burden, longing for family and social care and seeking different coping strategies are the main manifestations of the feelings.
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A phylogenetic tree is a visual diagram of the relationship between a set of biological species. The scientists usually use it to analyze many characteristics of the species. The distance-matrix methods, such as Unweighted Pair Group Method with Arithmetic Mean and Neighbor Joining, construct a phylogenetic tree by calculating pairwise genetic distances between taxa. These methods have the computational performance issue. Although several new methods with high-performance hardware and frameworks have been proposed, the issue still exists. In this work, a novel parallel Unweighted Pair Group Method with Arithmetic Mean approach on multiple Graphics Processing Units is proposed to construct a phylogenetic tree from extremely large set of sequences. The experimental results present that the proposed approach on a DGX-1 server with 8 NVIDIA P100 graphic cards achieves approximately 3-fold to 7-fold speedup over the implementation of Unweighted Pair Group Method with Arithmetic Mean on a modern CPU and a single GPU, respectively.
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Objective:To investigate the regulating molecules and acting mechanism of TAB182 in HR pathway.Methods:TAB182 in human breast cancer MCF-7 cells was knocked down by shRNA strategy, the TAB182 knockdown MCF-7 as the TAB182 knockdown group, and the MCF-7 cell using the shRNA negative control as the TAB182 negative control group. RNA sequencing and qRT-PCR were performed to screen and verify the differentially expressed genes of HR pathway related to TAB182 depression. Western blot was used to detect protein expression. Immunofluorescence staining of nuclear RAD51 and BrdU was used to check the 3′ ssDNA formation by the end resection. The cell cycle arrest and apoptosis were measured by flow cytometry. Cloning formation assay was used to evaluate the sensitivity TAB182-knockdown cells to radiation.Results:Both quantitative RNA sequencing and qRT-PCR assays showed that TAB182-knockdown significantly decreased the mRNA expression of RPA2( t=17.97, P<0.05). Compared with the TAB182 negative control group, the protein level of RPA2, the number of RAD51 foci, and the 3′ ssDNA-binding nuclear protein marker BrdU in TAB182-knockdown cells were significantly reduced. At 4, 8, and 12 h after actinomycin D treatment, the attenuation of RPA2 mRNA in the TAB182-knockdown cells was accelerated ( t=5.37, 3.79, 3.69, P<0.05). Compared with the TAB182 negative control group, the radiosensitivity and radiation-induced apoptosis in the TAB182-knockdown group were increased ( t=3.48, 11.05, P<0.05), and at 24 h after irradiation, the cell cycle block time was prolonged ( t=8.40, P<0.01). Conclusions:TAB182 plays a role in maintaining RPA2 mRNA stability, thereby promoting HR repair. TAB182 knockdown cells are highly sensitive to ionizing radiation.
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OBJECTIVE@#To compare the clinical efficacy between acupuncture combined with western medication and simple western medication for ocular myasthenia gravis (OMG), and to explore its possible mechanism.@*METHODS@#A total of 60 patients of ocular myasthenia gravis were randomized into an acupuncture combined with western medication group (30 cases, 1 case dropped off) and a western medication group (30 cases, 2 cases dropped off). Oral pyridostigmine bromide tablet and prednisone acetate tablet were given in the western medication group. On the basis of the treatment in the western medication group, Tongdu Tiaoqi acupuncture (acupuncture for unblocking the governor vessel and regulating qi ) was applied at Baihui (GV 20), Fengfu (GV 16), Hegu (LI 4), Zusanli (ST 36), etc. in the acupuncture combined with western medication group, once a day, 6 days a week. The treatment was given 8 weeks in both groups. Before and after treatment, the OMG clinical absolute score was observed, electrophysiological indexes of orbicularis oculi (value of mean jitter, percentage of jitter >55 μs and percentage of blocks) were measured by single-fiber electromyography (SFEMG), serum levels of acetylcholine receptor antibody (AChR-Ab), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were detected by ELISA method.@*RESULTS@#After treatment, the OMG clinical absolute scores, values of mean jitter, percentages of jitter >55 μs, percentages of blocks and serum levels of AChR-Ab, IFN-γ and IL-4 were decreased compared before treatment in both groups (P<0.05), and those in the acupuncture combined with western medication group were lower than the western medication group (P<0.05).@*CONCLUSION@#Acupuncture combined with western medication can effectively improve ptosis, palpebra superior fatigability, eye movement disorder and neuromuscular junction dysfunction in patients with ocular myasthenia gravis, the therapeutic effect is superior to simple western medication. Its mechanism may be related to down-regulating serum levels of AChR-Ab, IFN-γ and IL-4 and promoting the recovery of orbicularis oculi function.
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Humanos , Terapia por Acupuntura , Músculos Faciais , Interferon gama , Interleucina-4 , Miastenia Gravis/tratamento farmacológicoRESUMO
ObjectiveTo explore the structural characteristics and functional differences of intestinal flora in patients with type 2 diabetes mellitus (T2DM) of dampness heat trapping spleen(DHTS) syndrome and Qi-Yin deficiency(QYD) syndrome. MethodFrom June 2018 to January 2020,62 T2DM patients with DHTS syndrome and 60 with QYD syndrome were selected from Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Serum and fecal samples were collected to compare body mass index(BMI),glucose and lipid metabolism,fasting insulin (FINS) and fasting C-peptide (FCP) levels,and homeostasis model assessment of insulin resistance(HOMA-IR) of the two syndrome types. Fecal samples were extracted for DNA database construction,and 16S rDNA high-throughput sequencing was used to analyze and compare the intestinal flora and metabolic pathways. Result① The BMI,fasting plasma glucose(FPG),2-hour postprandial blood glucose (2 h PBG),total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),FINS,FCP,and HOMA-IR were higher in patients with DHTS syndrome than in patients with QYD syndrome,and the high density lipoprotein(HDL) of the former was lower than that of the latter,(P<0.05,P<0.01). ② In terms of species composition and differences,Bacteroidetes, Clostridia and Gammaproteobacteria were dominant at the class level,and the relative abundance of Clostridia,Mollicutes and Verrucomicrobiae in QYD syndrome group was higher than that in DHTS syndrome group. At the order level,Bacteroidales,Clostridiales and Enterobacteriales were mainly found. The relative abundance of Clostridiales,Erysipelotrichales and Verrucomicrobiales in QYD syndrome group was obviously higher than that in DHTS syndrome group,while Aeromonadales in the former was lower than that in the latter (P<0.05). At the family level,Bacteroidaceae,Prevotellaceae and Ruminococcaceae were predominant. The relative abundance of Ruminococcaceae,Porphyromonadaceae and Erysipelotrichaceae in QYD syndrome group was higher than that in DHTS syndrome group(P<0.05). At the genus level,Bacteroides,Prevotella and Parabacteroides were mainly found. The relative abundance of Parabacteroides,Butyrivibrio and Ruminiclostridium in QYD syndrome group was higher than that in DHTS syndrome group,while that of Klebsiella and Megasphaera in DHTS syndrome group was higher than that in QYD syndrome group(P<0.05). ③ Through Venn analysis of operational taxonomic units(OTU),it was found that there were 49 OTUs in patients with DHTS syndrome patients and 47 OTUs in QYD syndrome patients. ④ The results of OTU β diversity and α analysis showed that Shannon and Simpson indexes had statistical differences,while Ace and Chao indexes had no statistical differences. The intestinal microbial diversity of patients with QYD syndrome was higher than that of patients with DHTS syndrome(P<0.05). The analysis of similarities (ANOSIM) showed that the difference of β diversity between the two groups was significant(P<0.05). ⑤ Linear discriminant analysis Effect Size(LEfSe) results demonstrated that Klebsiella,Megasphaera and Aeromonadales could be selected as the key biomarkers for DHTS syndrome; 14 bacteria such as Ruminiclostridium,Burkholderiaceae,Lautropia,Butyrivibrio,Erysipelotrichales can be selected as the key biomarkers for QYD syndrome. ⑥Functional annotation and analysis showed that the DHTS syndrome involved 9 metabolic pathways,including arginine and proline metabolism,lipopolysaccharide biosynthesis,nicotinic acid and nicotinamide metabolism,while the QYD syndrome involved 10 metabolic pathways,including acarbose and valinomycin biosynthesis,glucagon signaling pathway and NOD-like receptor signaling pathway. ConclusionThere are obvious differences in intestinal flora and functions in T2DM patients of DHTS syndrome and QYD syndrome,which can be used as reference for traditional Chinese medicine (TCM) syndrome differentiation and the target of TCM treatment.
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Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO2) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO2 at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery . Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.
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Animais , Cães , Septo Interatrial/cirurgia , Cateterismo Cardíaco/métodos , Hipertensão Pulmonar Primária Familiar , Comunicação Interatrial/cirurgia , Hipertensão Pulmonar , Hipertensão Arterial PulmonarRESUMO
【Objective】 To generate secreted frizzled-related protein 4 (SFRP4) transgenic mice and analyze their biological properties. 【Methods】 We generated SFRP4 transgenic mice by DNA microinjection and detected the expression of SFRP4 by qRT-PCR and Western blotting. 【Results】 SFRP4 transgenic mice were successfully generated by DNA microinjection. The expression of SFRP4 was dramatically increased in transgenic mice liver compared with that of wide type. 【Conclusion】 The transgenic mice model of SFRP4 was successfully established by DNA microinjection. It provides a good model for studying the function of SFRP4 and the mechanism of participating in metabolic diseases.
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Objective: To explore the impact of transcatheter aortic valve replacement (TAVR) on renal function in patients with severe aortic stenosis. Methods: This is a single-center retrospective study. Consecutive patients with severe aortic valve stenosis and received TAVR in Zhongshan Hospital from December 2014 to December 2019 were included. The patients were divided into four groups according to the estimate glomerular filtration rate (eGFR) measured at one day before TAVR, namely eGFR>90 ml·min-1·1.73m-2 group, 60<eGFR≤90 ml·min-1·1.73m-2 group, 30<eGFR≤60 ml·min-1·1.73m-2 group and eGFR≤30 ml·min-1·1.73m-2 group. The patients were also divided into acute renal function recovery (AKR) group, acute kidney injury (AKI) group and no change in renal function group according to renal function changes at 72 hours after TAVR. AKR was defined as eGFR increased by more than 25% of the baseline value at 72 hours after TAVR, and AKI was defined as eGFR decreased more than 25% of the baseline value at 72 hours after TAVR. The clinical data of each group were compared, and multivariate logistic regression analysis was performed to analyze the determinants responsible for renal function changes after TAVR. Results: A total of 217 patients were enrolled in this study. The age was (76.7±7.4) years and there were 86 females. The Society of Thoracic Surgeons score was (9.5±5.8). The proportions achieved AKR after TAVR were 0, 30.2% (35/116), 58.6% (41/70) and 75.0% (9/12) respectively in eGFR>90 ml·min-1·1.73m-2 group, 60<eGFR≤90 ml·min-1·1.73m-2 group, 30<eGFR≤60 ml·min-1·1.73m-2 group and eGFR≤30 ml·min-1·1.73m-2 group. A total of 3 patients (1.4%) suffered AKI, including 2 patients in 30<eGFR≤60 ml·min-1·1.73m-2 group and 1 patient in 60<eGFR≤90 ml·min-1·1.73m-2 group. The incidence of AKI in eGFR<60 ml·min-1·1.73m-2 group was 2.4% (2/82). Among the 217 patients, AKR occurred in 85(39.2%) patients, 3(1.4%) experienced AKI and renal function remained unchanged in 129 (59.4%) patients post TAVR. Body mass index (BMI), left ventricular end diastolic dimension (LVEDD) and preoperative eGFR were statistically different between the 3 groups (P<0.05). Multivariate logistic regression analysis showed that BMI (OR=5.54, 95%CI 1.04-29.58, P=0.045), preoperative LVEDD (OR=1.22, 95%CI 1.09-1.38, P=0.001) and preoperative eGFR (OR=2.23, 95%CI 2.04-2.55, P=0.004) were associated with non-AKR post TAVR. Conclusions: After TAVR, most patients show no change or improvement of renal function. BMI, preoperative LVEDD and eGFR are related to renal function change after TAVR.
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With the rapid growth of next generation sequencing technologies, such as Slex, more and more data have been discovered and published. To analyze such huge data the computational performance is an important issue. Recently, many tools, such as SOAP, have been implemented on Hadoop and GPU parallel computing architectures. BLASTP is an important tool, implemented on GPU architectures, for biologists to compare protein sequences. To deal with the big biology data, it is hard to rely on single GPU. Therefore, we implement a distributed BLASTP by combining Hadoop and multi-GPUs. The experimental results present that the proposed method can improve the performance of BLASTP on single GPU, and also it can achieve high availability and fault tolerance.