RESUMO
Incomplete lineage sorting (ILS) makes ancestral genetic polymorphisms persist during rapid speciation events, inducing incongruences between gene trees and species trees. ILS has complicated phylogenetic inference in many lineages, including hominids. However, we lack empirical evidence that ILS leads to incongruent phenotypic variation. Here, we performed phylogenomic analyses to show that the South American monito del monte is the sister lineage of all Australian marsupials, although over 31% of its genome is closer to the Diprotodontia than to other Australian groups due to ILS during ancient radiation. Pervasive conflicting phylogenetic signals across the whole genome are consistent with some of the morphological variation among extant marsupials. We detected hundreds of genes that experienced stochastic fixation during ILS, encoding the same amino acids in non-sister species. Using functional experiments, we confirm how ILS may have directly contributed to hemiplasy in morphological traits that were established during rapid marsupial speciation ca. 60 mya.
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Marsupiais , Animais , Austrália , Evolução Molecular , Especiação Genética , Genoma , Marsupiais/genética , Fenótipo , FilogeniaRESUMO
Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.
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Macaca fascicularis , Transcriptoma , Animais , Comunicação Celular , Macaca fascicularis/genética , Receptores Virais/genética , Transcriptoma/genética , Via de Sinalização WntRESUMO
The accurate and complete assembly of both haplotype sequences of a diploid organism is essential to understanding the role of variation in genome functions, phenotypes and diseases1. Here, using a trio-binning approach, we present a high-quality, diploid reference genome, with both haplotypes assembled independently at the chromosome level, for the common marmoset (Callithrix jacchus), an primate model system that is widely used in biomedical research2,3. The full spectrum of heterozygosity between the two haplotypes involves 1.36% of the genome-much higher than the 0.13% indicated by the standard estimation based on single-nucleotide heterozygosity alone. The de novo mutation rate is 0.43 × 10-8 per site per generation, and the paternal inherited genome acquired twice as many mutations as the maternal. Our diploid assembly enabled us to discover a recent expansion of the sex-differentiation region and unique evolutionary changes in the marmoset Y chromosome. In addition, we identified many genes with signatures of positive selection that might have contributed to the evolution of Callithrix biological features. Brain-related genes were highly conserved between marmosets and humans, although several genes experienced lineage-specific copy number variations or diversifying selection, with implications for the use of marmosets as a model system.
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Callithrix/genética , Diploide , Evolução Molecular , Genoma/genética , Genômica/normas , Animais , Pesquisa Biomédica , Variações do Número de Cópias de DNA , Feminino , Mutação em Linhagem Germinativa/genética , Haplótipos/genética , Heterozigoto , Humanos , Mutação INDEL/genética , Masculino , Padrões de Referência , Seleção Genética , Diferenciação Sexual/genética , Cromossomo Y/genéticaRESUMO
New genome assemblies have been arriving at a rapidly increasing pace, thanks to decreases in sequencing costs and improvements in third-generation sequencing technologies1-3. For example, the number of vertebrate genome assemblies currently in the NCBI (National Center for Biotechnology Information) database4 increased by more than 50% to 1,485 assemblies in the year from July 2018 to July 2019. In addition to this influx of assemblies from different species, new human de novo assemblies5 are being produced, which enable the analysis of not only small polymorphisms, but also complex, large-scale structural differences between human individuals and haplotypes. This coming era and its unprecedented amount of data offer the opportunity to uncover many insights into genome evolution but also present challenges in how to adapt current analysis methods to meet the increased scale. Cactus6, a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions of highly duplicated sequences. Here we describe progressive extensions to Cactus to create Progressive Cactus, which enables the reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality. We describe results from an alignment of more than 600 amniote genomes, which is to our knowledge the largest multiple vertebrate genome alignment created so far.
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Genoma/genética , Genômica/métodos , Alinhamento de Sequência/métodos , Software , Vertebrados/genética , Âmnio , Animais , Simulação por Computador , Genômica/normas , Haplótipos , Humanos , Controle de Qualidade , Alinhamento de Sequência/normas , Software/normasRESUMO
Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1-4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.
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Aves/classificação , Aves/genética , Genoma/genética , Genômica/métodos , Genômica/normas , Filogenia , Animais , Galinhas/genética , Conservação dos Recursos Naturais , Conjuntos de Dados como Assunto , Tentilhões/genética , Humanos , Seleção Genética/genética , Sintenia/genéticaRESUMO
OBJECTIVES: Due to the impact of COVID-19 epidemic, face-to-face follow-up treatments for patients with chronic pain and implanted spinal cord stimulation (SCS) devices are forced to be delayed or stopped. This has led to more follow ups being done remotely. Meanwhile, with the development of 4G/5G networks, smartphones, and novel devices, remote programming has become possible. Here, we investigated the demand and utility of remote follow-ups including remote programming for SCS for patients with chronic pain. MATERIALS AND METHODS: A questionnaire including questions on demographic characteristics, pain history, postimplantation life quality, standard follow-up experience, remote follow-up, and remote programming experience was sent to patients diagnosed as chronic intractable pain and treated with SCS during January 2019 to January 2020. RESULTS: A total of 64 participants completed the questionnaire. About 70% of participants expressed demands for remote follow-ups due to the inconvenience, high costs, and time consumption of traditional follow-up visits. Nearly 97% of participants have attempted remote follow-ups, and about 81% of participants have further tried remote programming. Approximately, 96% of them recognized the benefits. CONCLUSIONS: The remote programming was in high demand among participants. Most of the participants have tried remote follow-ups or even remote programming. The remote programming appeared to be more efficient, economic and were widely recognized among participants.
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COVID-19/prevenção & controle , Dor Crônica/terapia , Surtos de Doenças/prevenção & controle , Neuroestimuladores Implantáveis , Tecnologia de Sensoriamento Remoto/métodos , Estimulação da Medula Espinal/métodos , Adulto , COVID-19/epidemiologia , China/epidemiologia , Dor Crônica/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodosRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women. Multiple susceptible gene as well as environmental factors and their interaction each other are contributed to the PCOS risk. Several case-control studies have researched the associations of the vitamin D receptor gene (VDR) polymorphisms with PCOS susceptibility, but the jury is still out. Here, we carried out a meta-analysis to clarify polymorphisms between ApaI (C/A) (rs7975232), BsmI (G/A) (rs1544410), FokI (C/T) (rs10735810), TaqI (T/C) (rs731236) and Tru9I (G/A) (rs757343) in the VDR gene and PCOS susceptibility based on relative lager sample size. METHODS: English database of PubMed and Embase, and Chinese database of Wanfang and China National Knowledge Infrastructure (CNKI) databases were retrivaled for the relationship between VDR gene variates and PCOS susceptibility published before 31th, May 2018. Crude odds ratios (ORs) and its 95% confidence intervals (95% CIs) in different comparisons were used to detected the strength of the association. All the statistical analyses of the present meta-analysis were performed by STATA version 12.0 software. RESULTS: Totally, 3587 (PCOS group 1922; control group 1665) participants from 13 studies were included which met our inclusion criteria. A statistically significant association between VDR ApaI (rs7975232) polymorphism and PCOS susceptibility (C vs. A: OR = 1.19, 95%CI = 1.06~1.34, P = 0.004) was found in the overall population. After stratified by ethnicity, we showed that there is a significant association between VDR ApaI (rs7975232) polymorphism and susceptibility to PCOS in the Asian (C vs. A: OR = 1.21, 95%CI = 1.04~1.42, P = 0.016) population, but this association was not found in the Caucasian population. Additionally, a significant relationship between VDR BsmI (rs1544410) variates with PCOS susceptibility in the Asian (G vs. A: OR = 1.27, 95%CI = 1.06~1.53, P = 0.011) population, but this association was not found in the Caucasian population. We didn't find any association between VDR FokI (rs2228570), VDR TaqI (rs731236), VDR Tru9I (rs757343) and PCOS susceptibility in the overall and the subgroup populations. CONCLUSIONS: Our findings demonstrated that VDR ApaI (rs7975232) and VDR BsmI (rs1544410) polymorphisms are correlated with susceptibility to PCOS in the Asian population and VDR TaqI (rs731236), VDR FokI (rs2228570), VDR Tru9I (rs757343) did not reveal a relationship with the PCOS susceptibility.
Assuntos
Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Síndrome do Ovário Policístico/etnologia , População Branca/genéticaRESUMO
OBJECTIVE: The study aimed to investigate the impact of the peak E2 level during controlled ovarian hyperstimulation (COS) on the cumulative live birth rate (cLBR) in non-PCOS women with normal ovarian reserve. MATERIALS AND METHODS: Women between 20 and 39 years were included. Donor cycles and patients who never experienced embryo transfer were excluded. Multivariable regression and smooth curve fitting were applied for statistical analysis. RESULTS: A total of 1141 patients were included. The mean age, basal AFC, peak E2 level, and number of retrieved oocyte were 30.0 ± 3.7 years old, 16.8 ± 6.7, 3911.0 ± 1302.9 pg/ml, and 13.6 ± 5.5, respectively. In the overall population of the cohort, cLBR, miscarriage rate, and preterm birth rate were 66.9%, 7.4%, and 13.7%, respectively. The results of multivariable regression analysis failed to show the impact of peak E2 on the cLBR [OR (95%CI) 0.995 (0.982, 1.009), P = 0.486]. However, the result of smooth curve fitting indicated that when the peak E2 was lower than 2185 pg/ml, the cLBR increased about 12% with 100 pg/ml increasing of the peak E2. When the peak E2 was higher than 6136 pg/ml, the cLBR decreased about 10% with 100 pg/ml increasing of the peak E2. CONCLUSION: We concluded that the peak E2 level on hCG trigger day is associated with the cLBR in a segmental pattern. There should be an appropriate range of the peak E2 level during COS to achieve a relative best cLBR in non-PCOS patients using stimulating protocol mainly based on GnRH agonist; however, the cutoff value must vary in different centers.
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Estradiol/metabolismo , Síndrome de Hiperestimulação Ovariana/metabolismo , Aborto Espontâneo/metabolismo , Adulto , Coeficiente de Natalidade , Estudos de Coortes , Transferência Embrionária/métodos , Estrogênios/metabolismo , Feminino , Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Nascido Vivo , Recuperação de Oócitos/métodos , Reserva Ovariana/fisiologia , Indução da Ovulação/métodos , Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas/métodos , Adulto JovemRESUMO
Cancer is an evolutionary process shaped by selective pressure from the microenvironments. However, recent studies reveal that certain tumors undergo neutral evolution where there is no detectable fitness difference amongst the cells following malignant transformation. Here, through computational modeling, we demonstrate that negative frequency-dependent selection (or NFDS), where the immune response against cancer cells depends on the clonality of neoantigens, can lead to an immunogenic landscape that is highly similar to neutral evolution. Crucially, NFDS promotes high antigenic heterogeneity and early immune evasion in hypermutable tumors, leading to poor responses to immune checkpoint blockade (ICB) therapy. Our model also reveals that NFDS is characterized by a negative association between average clonality and total burden of neoantigens. Indeed, this unique feature of NFDS is common in the whole-exome sequencing (WES) datasets (357 tumor samples from 275 patients) from four melanoma cohorts with ICB therapy and a non-small cell lung cancer (NSCLC) WES dataset (327 tumor samples from 100 patients). Altogether, our study provides quantitative evidence supporting the theory of NFDS in cancer, explaining the high prevalence of neutral-looking tumors. These findings also highlight the critical role of frequency-dependent selection in devising more efficient and predictive immunotherapies.
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Antígenos de Neoplasias , Imunoterapia , Evasão Tumoral , Humanos , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/genética , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Melanoma/imunologia , Melanoma/terapia , Melanoma/genética , Melanoma/tratamento farmacológico , Microambiente Tumoral/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapiaRESUMO
BACKGROUND: Spinal cord stimulation (SCS) is a surgical technique used in patients with chronic intractable pain, and its effectiveness and safety have been validated by multiple studies. However, to maintain an optimal and steady long-term effect is still challenging. Here, we report a new management paradigm integrating smartphone application and remote programming. Chronic pain patients with SCS implants can monitor their pain status on the phone and change stimulation parameters accordingly. The PreMaSy study is a randomized controlled trial to evaluate the clinical effectiveness and safety of this precise management system. METHODS: Patients with chronic intractable pain will be screened for eligibility, and 82 participants are anticipated to be enrolled in this trial. After the electrode implantation, the stimulation effectiveness will be tested. Participants with a reduction of more than 50% in the visual analog scale (VAS) will receive implantation of an implantable pulse generator and randomized (1:1) into the experimental group or control group. All participants will be asked to take online follow-ups and complete assessments using a smartphone application. Daily pain characteristic assessments and monthly quality of life questionnaires are integrated into the App, and participants will be required to complete these assessments. The daily VAS for pain intensity will be monitored and a threshold will be set based on baseline VAS score. The interventional appointment will be scheduled once the threshold is reached. The primary outcome is the health condition and quality of life assessed by the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). Utility values of EQ-5D-5L will be assessed at baseline and 1, 3, and 6 months post-operative. DISCUSSION: The PreMaSy study aims to evaluate the effectiveness and safety of a novel App-based, patient-centered, self-assessment management system for chronic intractable pain. A randomized controlled trial is designed to test the non-inferiority of this precise management system compared to the monthly online follow-ups. It is also expected to yield valuable experiences regarding precision medicine. TRIAL REGISTRATION: ClinicalTrials.gov NCT05761392. Registered on March 07, 2023.
Assuntos
Dor Crônica , Dor Intratável , Estimulação da Medula Espinal , Humanos , Estimulação da Medula Espinal/efeitos adversos , Dor Crônica/diagnóstico , Dor Crônica/terapia , Qualidade de Vida , Próteses e Implantes , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Alleles that cause advantageous phenotypes with positive selection contribute to adaptive evolution. Investigations of positive selection in protein-coding genes rely on the accuracy of orthology, models, the quality of assemblies, and alignment. Here, based on the latest genome assemblies and gene annotations, we present a comparative analysis on positive selection in four great ape species and identify 211 high-confidence positively selected genes (PSGs). Even the differences in population size among these closely related great apes have resulted in differences in their ability to remove deleterious alleles and to adapt to changing environments, we found that they experienced comparable numbers of positive selection. We also uncovered that more than half of multigene families exhibited signals of positive selection, suggesting that imbalanced positive selection resulted in the functional divergence of duplicates. Moreover, at the expression level, although positive selection led to a more non-uniform pattern across tissues, the correlation between positive selection and expression patterns is diverse. Overall, this updated list of PSGs is of great significance for the further study of the phenotypic evolution in great apes.
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Objective: To compare the cumulative live birth rates (cLBRs) after the first assisted reproductive technology (ART) cycle using flexible gonadotropin releasing hormone (GnRH)-antagonist protocol vs. standard long GnRH agonist protocol for controlled ovarian stimulation (COS) in infertile women with different ages and ovarian reserve. Methods: Women who underwent ART treatment at our center between June 1st, 2015 and December 31st, 2018 were screened. Among them, only women who underwent their first COS cycle with flexible GnRH antagonist protocol or standard long GnRH agonist protocol were included in this study. The main outcome measurement was cLBR. Results: A total of 4,402 patients were eligible for the analysis, of whom, 2,762 patients used the GnRH agonist protocol and 1,640 patients used the GnRH antagonist protocol. The cLBRs of women in the antagonist protocol group and long agonist protocol group were 45.3 and 50.0%, respectively. Subgroup multivariable regression analysis showed that, in patients with low ovarian reserve (AFC ≤ 7), the cLBR was significantly lower in the antagonist group than in the long agonist protocol group [OR (95% CI) 0.62 (0.41, 0.94)], which effect was more robust in younger patients (<30 y) [OR (95% CI) 0.29 (0.11, 0.74)]. The analysis also revealed remarkably lower cLBR in patients above 40 years regardless of their AFC, although the difference was not statistically significant. However, in patients with high ovarian reserve (AFC >24), the cLBR was higher in cycles with antagonist protocol than with the long agonist protocol [OR (95% CI) 1.43 (0.96, 2.12)], and the effect was of statistical significance in younger patients (< 30 y) [OR (95% CI) 1.78 (1.07, 2.96)]. Conclusion: The present study suggests that the flexible GnRH antagonist protocol might not be suitable for patients with low ovarian reserve (AFC ≤ 7) or patients aged over 40 years. However, flexible GnRH antagonist protocol might be strongly recommended for patients under 30 years old and with high ovarian reserve (AFC > 24). For the rest groups of patients in the present cohort, antagonist protocol was slightly favored because it had lower OHSS in general and in patients with poly-cystic ovarian syndrome (PCOS) according to previous publications.
Assuntos
Coeficiente de Natalidade/tendências , Hormônio Liberador de Gonadotropina/administração & dosagem , Infertilidade Feminina/terapia , Nascido Vivo , Reserva Ovariana , Técnicas de Reprodução Assistida/estatística & dados numéricos , Adulto , Feminino , Seguimentos , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos , Indução da Ovulação , Gravidez , Taxa de Gravidez , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
As COVID-19 rampages throughout the world and has a major impact on the healthcare system, non-emergency medical procedures have nearly come to a halt due to appropriate resource reallocation. However, pain never stops, particularly for patients with chronic intractable pain and implanted spinal cord stimulation (SCS) devices. The isolation required to fight this pandemic makes it impossible for such patients to adjust the parameters or configuration of the device on site. Although telemedicine has shown a great effect in many healthcare scenarios, there have been fewer applications of such technology focusing on the interaction with implanted devices. Here, we introduce the first remote and wireless programming system that enables healthcare providers to perform video-based real-time programming and palliative medicine for pain patients with a SCS implant. During the COVID-19 pandemic from January 23, 2020, the date of lockdown of Wuhan, to April 30, 2020, 34 sessions of remote programming were conducted with 16 patients. Thirteen of the 16 patients required programming for parameter optimization. Improvement was achieved with programming adjustment in 12 of 13 (92.3%) cases. Eleven of the 16 (68.8%) patients reported that the system was user-friendly and met their needs. Five patients complained of an unstable connection resulting from the low network speed initially, and three of these patients solved this problem. In summary, we demonstrated that a remote wireless programming system can deliver safe and effective programming operations of implantable SCS device, thereby providing palliative care of value to the most vulnerable chronic pain patients during a pandemic. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, identifier NCT03858790.
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OBJECTIVE: To investigate the role of endometrial macrophages in embryo implantation and in regulating the expression of vascular endothelial growth factor A (VEGFA) in mouse endometrium during the peri-implantation period. METHOD: At D3.5 (D0.5 defined as the morning when a vaginal plug was observed), pregnant mice were divided randomly into experimental group, control group and blank group. In the experimental group, the mice were subjected to intrauterine injection of clodronate liposomes on the left side of uterus to eliminate the macrophages, and PBS liposomes on the right side. PBS liposomes and PBS were administered in the control and blank groups, respectively. The uterine tissues were collected on D5.5 and stained with trypan blue to show the implantation sites. Flow cytometry was performed to examine the percentage of F4/80(+) CD11b(+) macrophages macrophages in the uterus. F4/80(+) macrophage population within the endometrium and ovary and changes in VEGFA expression at the implantation and non-implantation sites were examined using immunohistochemistry. RESULTS: Endometrial F4/80(+) CD11b(+) macrophages macrophages were significantly reduced by 74% following intrauterine injection of clodronate liposomes (P<0.05). The number of macrophages in the ovaries showed no significant difference among the 3 groups. In the experimental group, the left side of the uterine showed imcomplete cavity closure with a lower number of implantation site than the right side (2.20∓1.81 vs 5.10∓1.91, P<0.05). VEGFA expression at the implantation site were significantly decreased in the endometrium on the left side with macrophage suppression as compared with that on the right side (P<0.05). CONCLUSION: Endometrial macrophages appear to modulate uterine receptivity by regulating the expression of VEGFA to affect embryo implantation, suggesting the important role of macrophages in embryo implantation.
Assuntos
Implantação do Embrião , Endométrio/fisiologia , Macrófagos/citologia , Útero/citologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Animais , Feminino , Imuno-Histoquímica , Camundongos , Ovário/citologia , Gravidez , Distribuição AleatóriaRESUMO
OBJECTIVE: To investigate the effect of prostaglandins E2 (PGE2) in enhancing vascular endothelial growth factor (VEGF) expression in a rat macrophage cell line and the effect of the media from PGE2-inuced rat macrophages on angiogenetic ability of human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: Western blotting and qPCR were employed to investigate the expressions of VEGF protein and mRNAs in rat macrophage cell line NR8383 stimulated by PGE2 in the presence or absence of EP2 receptor inhibitor (AH6809) and EP4 receptor inhibitor (AH23848). Conditioned supernatants were obtained from different NR8383 subsets to stimulate HUVECs, and the tube formation ability and migration of the HUVECs were assessed with Transwell assay. RESULTS: PGE2 stimulation significantly enhanced the expression of VEGF protein and mRNAs in NR8383 cells in a dose-dependent manner. The supernatants from NR8383 cells stimulated by PGE2 significantly enhanced tube formation ability of HUVECs (P<0.05) and promoted the cell migration. Such effects of PGE2 were blocked by the application of AH6809 and AH23848. CONCLUSION: PGE2 can dose-dependently increase VEGF expression in NR8383 cells, and the supernatants derived from PGE2-stimulated NR8383 cells can induce HUVEC migration and accelerate the growth of tube like structures. PGE2 are essential to corpus luteum formation by stimulating macrophages to induce angiogenesis through EP2/EP4.
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Meios de Cultivo Condicionados/farmacologia , Dinoprostona/farmacologia , Células Endoteliais da Veia Umbilical Humana/citologia , Macrófagos/química , Animais , Linhagem Celular , Movimento Celular , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Neovascularização Patológica , RNA Mensageiro , Ratos , Receptores de Prostaglandina E Subtipo EP2/metabolismo , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Fator A de Crescimento do Endotélio Vascular , Xantonas/farmacologiaRESUMO
BACKGROUND: The use of antibiotics is considered a major determinant of the development of resistance in organisms. This study assessed current patterns of antibiotic prescription and provides background for quality improvement in general hospitals in Hubei, China. METHODS: A point-prevalence study was performed in November 2008. All inpatients on the day of the survey were included in the analysis. RESULTS: On the day of the study, 6904 patients (56%) were receiving antibiotic therapy; the highest rate occurred in the ICU (90%), and the lowest occurred in the medical wards (39%). The most commonly used antibiotics were ß-lactam antibiotics, including cephalosporins (40%) and piperacillin (19%), followed by fluoroquinolones (14%). CONCLUSIONS: Our data indicated a high rate of antibiotic use in Chinese hospitals. These findings suggest important areas for intervention and the implementation of antibiotic stewardship policies in Chinese hospitals. A multi-faceted strategy should be implemented at the national level in China and should include education, regulation, and greater financial support from the government.
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Antibacterianos/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Adulto , China/epidemiologia , Resistência Microbiana a Medicamentos , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Melhoria de QualidadeRESUMO
OBJECTIVE: To evaluate the impact of spermatozoa from different sources on normal fertilization of oocytes, embryo quality and embryo developmental potential in intracytoplasmic sperm injection (ICSI) cycles. METHODS: A retrospective analysis was conducted among 197 patients undergoing ICSI cycles in our center. The patients were classified into 3 groups according to the sources of semen, namely ejaculated spermatozoa group (n=102), percutaneous epididymal sperm aspiration (PESA) group (n=68), and testicular sperm aspiration (TESA) group (n=27). The ejaculated spermatozoa group was further classified into oligoasthenoteratozoospermia (n=67) and cryptozoospermia (n=35) subgroups. The normal fertilization, high-quality embryo, implantation and clinical pregnancy rates were compared among the groups; the rate of high-quality blastocyst formation in in-vitro culture of non-top quality embryos was also observed. RESULTS: The patients with PESA showed significantly higher normal fertilization rate (75.6%) than those in oligoasthenoteratozoospermia (64.8%), cryptozoospermia (62.1%), and TESA (61.6%) groups (P<0.05). No significant differences were found in the high-quality embryo, implantation, and clinical pregnancy rates among the groups (P>0.05). The rate of high-quality blastocyst formation in the in-vitro culture of non-top quality embryos was also comparable among the groups (P>0.05). CONCLUSION: Although spermatozoa obtained with by PESA is associated with a higher normal fertilization rate, the sources of spermatozoa do not significantly affect the embryonic quality and developmental potential in ICSI cycles.
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Fertilização , Injeções de Esperma Intracitoplásmicas , Recuperação Espermática , Espermatozoides , Astenozoospermia , Implantação do Embrião , Desenvolvimento Embrionário , Feminino , Fertilização in vitro , Humanos , Masculino , Oligospermia , Oócitos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , SêmenRESUMO
The objective of this study is to examine the change in macrophage numbers, inducible form of NO synthase (iNOS), and vascular endothelial growth factor (VEGF) expression both before and after embryo implantation in the uterine tissue of mice. In order to explore the mechanism of macrophages in endometrial angiogenesis, 8-week-old female mice were divided into three groups: pregnant group, pseudopregnant group (mated to male mice that had been vasectomized), and estrous group (unmated). Individuals from these three groups were sacrificed at time intervals D1.5 to D6.5. Formalin-fixed paraffin-embedded tissue was used for immunocytochemical localization of Mφ, iNOS, and VEGF utilizing standard methodology. The proportion of macrophages in the peripheral blood was determined by flow cytometry, and the relationship between macrophage, iNOS, and VEGF expression was analyzed. The proportion of peripheral blood macrophages in the pregnancy group was significantly higher than that in the other groups. The results of immunohistochemistry determined that the macrophages exhibited changes in both numbers and distribution. The number of macrophages in the endometrium of the pregnancy and pseudopregnancy groups was significantly higher than that in the control (estrous) group. In the pregnancy group, macrophage numbers dramatically decreased and gradually transferred to the perimetrium on D4.5. Immunostaining revealed strong staining in the pregnancy group and weaker staining in the pseudopregnant and control groups for both iNOS and VEGF. There was strong, dense immunostaining at the implantation site for both iNOS and VEGF, whereas light immunostaining was seen in interimplantation tissues on D5.5 to D6.5. In the pregnant group, peripheral blood and uterine macrophage proportions were negatively correlated, whereas the amount of macrophages, iNOS, and VEGF expression in the endometrium were positively correlated. The expression of iNOS and VEGF in the endometrium also displayed a strong positive correlation. In conclusion, during embryo implantation, macrophages levels decreased in the uterus, whereas the number of peripheral macrophages increased, suggesting that macrophages may migrate into the peripheral blood and uterus to adapt for pregnancy. Additionally, an increase in the expression of iNOS and VEGF was observed during the implantation window, implying that iNOS and VEGF may play an important role in promoting embryo implantation. The positive correlation between macrophages, iNOS, and VEGF in the implanting uterus implied that macrophages might regulate iNOS and VEGF during the implantation process.
Assuntos
Implantação do Embrião/fisiologia , Macrófagos/fisiologia , Útero/irrigação sanguínea , Útero/citologia , Animais , Feminino , Citometria de Fluxo , Imuno-Histoquímica , Masculino , Camundongos , GravidezRESUMO
Successive point-prevalence surveys were conducted annually from 2007 to 2011 to monitor the prevalence of healthcare-associated infections (HAIs) in a university hospital in Hubei Province in China. The surveys used the case definition criteria established by the Ministry of Health of the People's Republic of China. In the 5 surveys, the overall frequency of HAIs was 3.16% (301/9533). No significant differences were identified in the point prevalence measurements of HAIs in any of the years from 2007 to 2011. Of all the cases, proportionally, the most frequent infection site was the respiratory tract (2.34%), followed by surgical sites (0.43%) and urinary tract sites (0.28%). Gram-negative aerobic bacilli were the most common organisms mentioned; the most frequently isolated organism was Pseudomonas aeruginosa, followed by Escherichia coli and Acinetobacter baumannii. Approximately one-half of the patients were receiving antibiotics at the time of the surveys. Cephalosporin, penicillin, and quinolone were most commonly used for treatment or prevention. The differences found in HAI prevalence data across the 5 surveys given in the hospital were not statistically significant. In conclusion, this successive point-prevalence survey provides information about the trend of HAI prevalence, epidemical character, and the use of antibiotics among the university hospital's in-patients. This information allows us to initiate targeted programs for infection prevention and control.