RESUMO
Bats are associated with the circulation of most mammalian filoviruses (FiVs), with pathogenic ones frequently causing deadly hemorrhagic fevers in Africa. Divergent FiVs have been uncovered in Chinese bats, raising concerns about their threat to public health. Here, we describe a long-term surveillance to track bat FiVs at orchards, eventually resulting in the identification and isolation of a FiV, Dehong virus (DEHV), from Rousettus leschenaultii bats. DEHV has a typical filovirus-like morphology with a wide spectrum of cell tropism. Its entry into cells depends on the engagement of Niemann-Pick C1, and its replication is inhibited by remdesivir. DEHV has the largest genome size of filoviruses, with phylogenetic analysis placing it between the genera Dianlovirus and Orthomarburgvirus, suggesting its classification as the prototype of a new genus within the family Filoviridae. The continuous detection of viral RNA in the serological survey, together with the wide host distribution, has revealed that the region covering southern Yunnan, China, and bordering areas is a natural circulation sphere for bat FiVs. These emphasize the need for a better understanding of the pathogenicity and potential risk of FiVs in the region.
Assuntos
Quirópteros , Filoviridae , Animais , Filogenia , China , MamíferosRESUMO
T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Motivated by our previous finding that intron retention (IR) could lead to transcript instability, in this study, we performed BruChase-Seq to experimentally monitor the expression dynamics of nascent transcripts in resting and activated CD4+ T cells. Computational modeling was then applied to quantify the stability of spliced and intron-retained transcripts on a genome-wide scale. Beyond substantiating that intron-retained transcripts were considerably less stable than spliced transcripts, we found a global stabilization of spliced mRNAs upon T cell activation, although the stability of intron-retained transcripts remained relatively constant. In addition, we identified that La-related protein 4 (LARP4), an RNA-binding protein (RBP) known to enhance mRNA stability, was involved in T cell activation-dependent mRNA stabilization. Knocking out Larp4 in mice destabilized Nfκb1 mRNAs and reduced secretion of interleukin-2 (IL2) and interferon-gamma (IFNγ), two factors critical for T cell proliferation and function. We propose that coordination between splicing regulation and mRNA stability may provide a novel paradigm to control spatiotemporal gene expression during T cell activation.
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Interferon gama/genética , Interleucina-2/genética , Proteínas/genética , Estabilidade de RNA/genética , Transcriptoma/genética , Processamento Alternativo/genética , Animais , Humanos , Íntrons/genética , Ativação Linfocitária/genética , Camundongos , NF-kappa B/genética , Ligação Proteica/genética , RNA Mensageiro/genética , Linfócitos T/metabolismoRESUMO
During the dengue epidemic in Yunnan Province, China, during 2019, a concurrent outbreak of chikungunya occurred in the city of Ruili, which is located in the southwest of the province, adjacent to Myanmar. As part of this outbreak, three neonatal cases of infection with indigenous chikungunya virus from mother-to-child (vertical) transmission were observed. Isolates of chikungunya virus were obtained from 37 serum samples of patients with chikungunya during this outbreak, and a phylogenetic analysis of these isolates revealed that they belong to the Indian Ocean subclade of the East/Central/South African genotype. The E1 genes of these viruses did not harbor the A226V mutation.
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Febre de Chikungunya/virologia , Vírus Chikungunya/isolamento & purificação , Doenças Transmissíveis Emergentes/virologia , Transmissão Vertical de Doenças Infecciosas , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/transmissão , Vírus Chikungunya/classificação , Vírus Chikungunya/genética , China/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/transmissão , Surtos de Doenças , Feminino , Genoma Viral/genética , Genótipo , Humanos , Masculino , Mutação , Filogenia , RNA Viral/genética , Proteínas Virais/genéticaRESUMO
A distributed single-input multiple-output (SIMO) sonar system is composed of a sound source and multiple underwater receivers. It provides an important framework for underwater target localization. However, underwater hostile environments bring more challenges for underwater target localization than terrestrial target localization, such as the difficulties of synchronizing all the underwater receiver clocks, the varying underwater sound speed and the uncertainties of the locations of the underwater receivers. In this paper, we take the sound speed variation, the time synchronization and the uncertainties of the receiver locations into account, and propose the underwater target localization and synchronization (UTLS) algorithm for the distributed SIMO sonar system. In the distributed SIMO sonar system, the receivers are organized in a star topology, where the information fusion is carried out in the central receiver (CR). All the receivers are not synchronized and their positions are known with uncertainties. Moreover, the underwater sound speed is approximately modeled by a depth-dependent sound speed profile (SSP). We evaluate our proposed UTLS algorithm by comparing it with several benchmark algorithms via numerical simulations. The simulation results reveal the superiority of our proposed UTLS algorithm.
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Background: The significance of early neuraminidase inhibitor (NAI) therapy for treating influenza A(H7N9) is currently unknown. Methods: The duration of viral shedding was monitored by reverse-transcription polymerase chain reaction after patients with confirmed H7N9 infection were admitted to the First Affiliated Hospital, Zhejiang University, during April 2013-April 2017. Indices such as the length of hospitalization and mortality were collected, and the correlation between the time of administration of NAI and the severity of disease was systematically analyzed. Results: One hundred sixty patients with confirmed H7N9 infection were divided into 3 groups according to NAI starting time. Three of 20 (15%) patients for whom NAI was administered within 2 days died compared with 12 of 52 (23.1%) patients who received treatment within 2-5 days and 33 of 88 (37.5%) patients who were treated after 5 days (P < .05). The median durations of viral shedding from NAI therapy initiation was 4.5 days (interquartile range [IQR], 3-9 days) for patients who took antiviral medication within 2 days, which was significantly different from that for patients who took medication within 2-5 days (7.5 days [IQR, 4.25-12.75 days]) or after 5 days (7 days [IQR, 5-10 days]) (P < .05). We found that the duration of viral shedding from NAI therapy was the shortest in spring 2013 (5.5 days) and the longest in winter-spring 2016-2017 (8.5 days) (P < .05), showing a prolonged trend. Conclusions: Early NAI therapy within 2 days of illness shortened the duration of viral shedding and improved survival in patients with H7N9 viral infection.
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Antivirais/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Influenza Humana/tratamento farmacológico , Neuraminidase/antagonistas & inibidores , Eliminação de Partículas Virais/efeitos dos fármacos , Idoso , China , Feminino , Hospitalização , Humanos , Subtipo H7N9 do Vírus da Influenza A , Influenza Humana/mortalidade , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estações do Ano , Fatores de Tempo , Resultado do TratamentoRESUMO
While myeloid-derived suppressor cells (MDSCs) have been reported to participate in the promotion of angiogenesis and tumor growth, little is known about their presence and function during perioperative period. Here, we demonstrated that human MDSCs expressing CD11b(+), CD33(+) and HLA-DR(-) significantly increased in lung cancer patients after thoracotomy. CD11b(+) CD33(+) HLA-DR(-) MDSCs isolated 24 hr after surgery from lung cancer patients were more efficient in promoting angiogenesis and tumor growth than MDSCs isolated before surgical operation in allograft tumor model. In addition, CD11b(+) CD33(+) HLA-DR(-) MDSCs produced high levels of MMP-9. Using an experimental lung metastasis mouse model, we demonstrated that the numbers of metastases on lung surface and Gr-1(+) CD11b(+) MDSCs at postoperative period were enhanced in proportion to the degree of surgical manipulation. We also examined that syngeneic bone marrow mesenchymal stem cells (BMSCs) significantly inhibited the induction and proliferation of Gr-1(+) CD11b(+) MDSCs and further prevented lung metastasis formation in the mice undergoing laparotomy. Taken together, our results suggest that postoperatively induced MDSCs were qualified with potent proangiogenic and tumor-promotive ability and this cell population should be considered as a target for preventing postoperative tumor metastasis.
Assuntos
Proliferação de Células/genética , Neoplasias Pulmonares/terapia , Células Mieloides/transplante , Neovascularização Patológica/terapia , Animais , Antígeno CD11b/genética , Citometria de Fluxo , Antígenos HLA-DR/genética , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metaloproteinase 9 da Matriz/biossíntese , Camundongos , Metástase Neoplásica , Neovascularização Patológica/patologia , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Diarrhea is the second most common cause of death among children less than 5 years of age worldwide. The etiological agents of diarrhea in the southeast coastal area of China were studied from July 2009 to December 2014. METHODS: A total of the 2318 patients were enrolled in this study and examined for the presence of viruses, bacteria, and parasites. Multiplex real-time PCR was used for the detection of diarrheagenic Escherichia.coli (DEC). DEC strains were tested for susceptibility to a panel of 20 antibiotics using the Kirby-Bauer disc-diffusion method. RESULTS: Of the 2318 children with diarrhea, 962 (41.5 %) were positive for at least one pathogen. Rotavirus, human calicivirus (HucV), and DEC were predominant, with detection rates of 19.1 % (443), 17.7 % (411), and 7.6 % (177), respectively. The prevalences of various pathogens in patients of different ages and in different seasons were not the same. The resistance rates of 177 strains of DEC to ampicillin, tetracycline, and cefazolin were 93.2 %, 60.0 %, and 57.7 %, respectively. CONCLUSIONS: Rotavirus, HucV, and DEC were the main pathogens associated with diarrhea in Zhejiang, China. DEC possessed high levels of antibiotic resistance. Increased monitoring of etiological agents of diarrhea is necessary.
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Infecções por Caliciviridae/epidemiologia , Diarreia/virologia , Infecções por Escherichia coli/epidemiologia , Infecções por Rotavirus/epidemiologia , Ampicilina , Antibacterianos , Pré-Escolar , China/epidemiologia , Diarreia/epidemiologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Escherichia coli/fisiologia , Feminino , Humanos , Lactente , Masculino , Vigilância da População , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Rotavirus/isolamento & purificação , Estações do Ano , TetraciclinaRESUMO
Interleukin (IL)-35 is an inhibitory cytokine consisting of IL-12A and Epstein-Barr virus-induced gene 3 (Ebi3) and is required by regulatory T-cells (Tregs) for maximal activity. During chronic hepatitis B virus (HBV) infection, Tregs have immunosuppressive effects on HBV-specific T helper (Th) cells, yet little is known about the complex regulation of Tregs and their contribution to the inadequate immune system response to the virus. In the present study, we investigated whether IL-35 is involved in HBV-related cellular immune responses. Cluster of differentiation (CD)4(+) T-cells from peripheral blood were derived from healthy volunteers, resolved HBV individuals and chronic active hepatitis B patients and stimulated with CD3/28-conjugated beads. We analysed mRNA and protein levels of IL-35 and assessed the inhibitory effect of IL-35 on HBV core antigen-specific cytotoxic T lymphocytes (CTLs), dendritic cells (DCs) and effector T-cells (Teffs). Correlation analyses between liver inflammation and HBV DNA load were conducted. Results show that chronic HBV patients harbour significantly higher levels of Ebi3 mRNA and protein in CD4(+) T-cells compared with healthy volunteers and resolved HBV individuals. IL-35 suppressed the proliferation of HBV antigen-specific CTLs and interferon (IFN)-γ production in vitro. Ex vivo, IL-35 decreased the proliferation of CD4(+)CD45RA(+) naïve T-cells, especially in CD4(+)CD25(-)CD45RA(+) naïve Teffs. IL-35 inhibited the expansion of CD11c(+) DCs. Our data indicate that IL-35 is highly expressed in chronic HBV CD4(+) T-cells and plays an important role in the inhibition of the cellular immune response in chronic HBV.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Vírus da Hepatite B/imunologia , Imunidade Celular , Interferon gama/imunologia , Subunidade p35 da Interleucina-12/imunologia , Interleucinas/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , DNA Viral/sangue , Células Dendríticas/imunologia , Células Dendríticas/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Hepatite B Crônica/metabolismo , Hepatite B Crônica/virologia , Humanos , Interferon gama/metabolismo , Subunidade p35 da Interleucina-12/genética , Subunidade p35 da Interleucina-12/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Ativação Linfocitária , Antígenos de Histocompatibilidade Menor , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Citotóxicos/virologia , Carga ViralRESUMO
BACKGROUND: In recent years novel human respiratory disease agents have been described for Southeast Asia and Australia. The causative pathogens were classified as pteropine orthoreoviruses with a strong phylogenetic relationship to orthoreoviruses of bat origin. RESULTS: In this report, we isolated a novel Melaka-like reovirus (named "Cangyuan virus") from intestinal content samples of one fruit bat residing in China's Yunnan province. Phylogenetic analysis of the whole Cangyuan virus genome sequences of segments L, M and S demonstrated the genetic diversity of the Cangyuan virus. In contrast to the L and M segments, the phylogenetic trees for the S segments of Cangyuan virus demonstrated a greater degree of heterogeneity. CONCLUSIONS: Phylogenetic analysis indicated that the Cangyuan virus was a novel orthoreovirus and substantially different from currently known members of Pteropine orthoreovirus (PRV) species group.
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Quirópteros/virologia , Orthoreovirus/genética , Orthoreovirus/isolamento & purificação , Animais , China , Variação Genética/genética , Genoma Viral/genética , Filogenia , RNA Viral/genética , Análise de Sequência de DNA/métodosRESUMO
Hepatitis, cirrhosis and hepatocellular carcinoma caused by hepatitis B virus (HBV) infection has threatening human health seriously. As HBV is a kind of non-cytotoxic virus, host immune response plays a vital role in pathogenesis and clinical outcomes of hepatitis B. Multiple immune cells (e.g., including cytotoxic T lymphocytes, regulatory T cells, natural killer cells, dendritic cells) are important in the immune regulation of HBV infection. Therefore, focusing on the activation states of immune cells may provide new evidences and strategies for determining immune status of HBV infectors, monitoring progression of diseases and predicting efficacy of antiviral treatment.
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Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Imunidade Celular , HumanosRESUMO
AIM: Hepatitis B surface antigen (HBsAg) has become a marker to judge immunological response to hepatitis B therapy. Quantified serum HBsAg levels can predict the response to pegylated interferon and entecavir. In this study, we aimed to explore the correlation of serum HBsAg levels with response to telbivudine (LdT) treatment in patients with chronic hepatitis B (CHB). METHODS: Seventy-three treatment-naive CHB patients were recruited and received LdT monotherapy for 52 weeks and serial HBsAg levels were measured at five protocol time points. According to therapeutic efficacy at week 52, three subgroups of patients were identified, including complete responders (CR), partial responders (PR) and non-responders (NR). RESULTS: After 52 weeks of treatment, CR, PR and NR represented 19 (26%), 33 (45%) and 21 (29%) patients in the sample of 73, respectively. The median values of baseline HBsAg (log10 IU/mL) were 4.05, 4.50 and 5.03 for CR, PR and NR, respectively. There was a distinct decline of HBsAg at week 52; median log10 HBsAg levels (IU/mL) were 3.61 (CR), 3.86 (PR) and 4.31 (NR). Positive correlation between HBsAg levels and HBV DNA loads was observed in the group of NR and early antiviral treatment of PR, but not in CR. CONCLUSION: Initial HBsAg level was closely correlated with the efficacy of LdT. Patients with low HBsAg levels presented satisfactory responses. Therefore, initial level and correlation with HBV DNA of the serum HBsAg levels could predict responsiveness in CHB patients receiving LdT.
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We detected Toxoplasma gondii in 29.3% (95% confidence interval [CI], 25.5% to 33.1%) of 550 insectivorous bats collected in Myanmar. The genotyping of these positive samples revealed they were closely related to or belong to clonal type I, which is highly virulent in mice, showing that these bats are potential reservoirs for T. gondii transmission.
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Quirópteros/parasitologia , Reservatórios de Doenças/parasitologia , Toxoplasma/genética , Toxoplasmose/epidemiologia , Animais , Primers do DNA/genética , Genótipo , Mianmar/epidemiologia , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Fragmento de Restrição , Prevalência , Toxoplasmose/genéticaRESUMO
BACKGROUND: Bloodstream infection is still an important cause for morbidity and mortality. In order to reduce the turnaround time for laboratory diagnosis of bacteremia, the efficacy of identification and antimicrobial susceptibility testing using samples taken directly from positive culture bottles by Vitek 2 compact and Kirby-Bauer disk diffusion method was evaluated. METHODS: A total of 218 monomicrobial blood cultures, including 81 Gram-negative and 137 Gram-positive isolates, were detected by a direct (that is, the organism was taken from the positive blood culture bottle) and standardized (taken from the overnight agar medium subculture) method on Vitek 2 compact ID cards for identification and Kirby-Bauer disk diffusion method for antimicrobial susceptibility testing. RESULTS: 79 of 81 Gram-negative rods (97.5%) and 84 of 137 Gram-positive cocci (61.3%) were correctly identified to the species level. Among 41 strains of wrongly identified Gram-positive cocci, 30 strains (73.2%) were misidentified as Kocuria. For antimicrobial susceptibility testing, the direct method had an overall error rate of 2.1% for Gram-negative rods, with 0.1% very major, 0.4% major, and 1.6% minor discrepancies compared with the standard method. The overall error rate for Gram-positive cocci was 4.4%, with 0.2% very major, 1.3% major, and 2.9% minor discrepancies. CONCLUSIONS: Direct identification and antibiotic susceptibility testing with samples taken directly from blood cultures provided excellent results for Gram-negative rods and decreased turnaround time, while it would be less reliable for identification of Gram-positive cocci, although their antibiotic susceptibility testing yielded very good results.
Assuntos
Antibacterianos/farmacologia , Bacteriemia/microbiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Testes de Sensibilidade Microbiana , HumanosRESUMO
Objectives: We analyzed the directional effect of perceived control and control strategies on subjective well-being in middle-aged and elderly people with historical data, and to provide data support for the intervention of well-being in the later years of the elderly group, so as to help them age successfully.Methods: Using data from the CLHLS between 2005 and 2014, we collected demographic and social data of the same elderly population over the decade. We also gathered information on changes in well-being, perceived control, and the use of control strategies. To analyze the longitudinal relationship between subjective well-being and perceived control, including the impact of control strategies on subjective well-being, we used a multilevel growth model with MPLUS. Results: We found that subjective well-being and perceived control were not affected by time. However, changes in perceived control in older adults could predict their level of subjective well-being. Those with higher initial levels of perceived control experienced greater increases in subjective well-being. Additionally, the use of control strategies had a significant influence on changes in subjective well-being, explaining 70.5% of the variance. Conclusion: Combined use of multiple control strategies is a feasible way to improve subjective well-being in later life.
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Comportamentos Relacionados com a Saúde , Pessoa de Meia-Idade , Humanos , Idoso , Estudos Longitudinais , Análise MultinívelRESUMO
BACKGROUND: Acute liver failure is one of the most intractable clinical problems. The use of bioartificial livers may solve donor shortage problems. Human umbilical cord mesenchymal stem cells (hUCMSCs) are an excellent seed cell choice for artificial livers because they change their characteristics to resemble hepatocyte-like cells (HLCs) following artificial liver transplantation. OBJECTIVE: This study aimed to determine whether the immunological characteristics of hUCMSCs are changed after being transformed into hepatocyte-like cells. METHODS: HUCMSCs were isolated by the adherent method. The following hUCMSC surface markers were detected using flow cytometry: CD45, CD90, CD105, CD34, and octamer-binding transcription factor 4 (OCT-4). Functional detection of adipogenic differentiation was performed. The hUCMSCs were cultured in complete medium (control group) or induction medium (induction group), and flow cytometry was used to detect cell surface markers. Peritoneal lavage fluid was collected after intraperitoneal injection of 1 × 106 cells/mouse over 40 minutes. The leukocyte count, labeled CD45, CD3, CD4 and CD8 antibodies, and flow detection of T lymphocyte subsets were determined using the peritoneal lavage fluid. RESULTS: Using phenotypic and functional identification, hUCMSCs were successfully isolated using a two-step induction method. The surface markers of the hUCMSCs cells changed after HLC induction. In vivo immune results showed that hUCMSCs and HLsC induced leukocyte production. CONCLUSION: Hepatic induction of hUCMSCs changes their cell surface markers. Both HLCs and hUCMSCs cause leukocytosis in vivo, but the immune response induced by HLCs is slightly stronger.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Animais , Camundongos , Diferenciação Celular , Fígado , Hepatócitos , Cordão Umbilical , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
BACKGROUND: The identification of new virus strains is important for the study of infectious disease, but current (or existing) molecular biology methods are limited since the target sequence must be known to design genome-specific PCR primers. Thus, we developed a new method for the discovery of unknown viruses based on the cDNA--random amplified polymorphic DNA (cDNA-RAPD) technique. Getah virus, belonging to the family Togaviridae in the genus Alphavirus, is a mosquito-borne enveloped RNA virus that was identified using the Virus-Discovery-cDNA RAPD (VIDISCR) method. RESULTS: A novel Getah virus was identified by VIDISCR from suckling mice exposed to mosquitoes (Aedes albopictus) collected in Yunnan Province, China. The non-structural protein gene, nsP3, the structural protein gene, the capsid protein gene, and the 3'-untranslated region (UTR) of the novel Getah virus isolate were cloned and sequenced. Nucleotide sequence identities of each gene were determined to be 97.1-99.3%, 94.9-99.4%, and 93.6-99.9%, respectively, when compared with the genomes of 10 other representative strains of Getah virus. CONCLUSIONS: The VIDISCR method was able to identify known virus isolates and a novel isolate of Getah virus from infected mice. Phylogenetic analysis indicated that the YN08 isolate was more closely related to the Hebei HB0234 strain than the YN0540 strain, and more genetically distinct from the MM2021 Malaysia primitive strain.
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Aedes/virologia , Infecções por Alphavirus/virologia , Alphavirus/classificação , Alphavirus/isolamento & purificação , DNA Complementar/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico/métodos , Virologia/métodos , Alphavirus/genética , Animais , Animais Recém-Nascidos , China , Clonagem Molecular , Análise por Conglomerados , DNA Viral/química , DNA Viral/genética , Modelos Animais de Doenças , Camundongos , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , Proteínas Virais/genéticaAssuntos
Análise Química do Sangue , Creatina Quinase/sangue , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Humana/sangue , Influenza Humana/patologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Influenza Humana/complicações , Influenza Humana/enzimologia , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/mortalidade , Índice de Gravidade de Doença , Análise de Sobrevida , Fatores de TempoRESUMO
Currently, patients with esophageal cancer, especially advanced patients, usually use autologous tissue for esophageal alternative therapy. However, an alternative therapy is often accompanied by serious complications such as ischemia and leakage, which seriously affect the prognosis of patients. Tissue engineering has been widely studied as one of the ideal methods for the treatment of esophageal cancer. In view of the complex multi-layer structure of the natural esophagus, how to use the tissue engineering method to design the scaffold with structure and function matching with the natural tissue is the principle that the tissue engineering method must follow. This article will analyze and summarize the construction methods, with or without cells, and repair effects of single-layer scaffold and multi-layer scaffold. Especially in the repair of full-thickness and circumferential esophageal defects, the flexible design method and the binding force between the layers of the scaffold are very important. In short, esophageal tissue engineering technology has broad prospects and plays a more and more important role in the treatment of esophageal diseases.
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The most common EGFR mutations in non-small cell lung cancer are exon 19 deletions and exon 21 point mutations, which are both sensitive to EGFR-tyrosine kinase inhibitors. However, rare EGFR mutations do exist and how these mutations respond to tyrosine kinase inhibitors is not well understood. A Chinese woman diagnosed with stage IV lung adenocarcinoma harbored a rare EGFR L747P (2239-2240 TT > CC) mutation, and treatment with gefitinib and osimertinib failed to achieve the desired effect. Herein, possible correlations between gene analysis and the outcomes of subsequent treatment are discussed.
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Adenocarcinoma de Pulmão/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Acrilamidas , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Compostos de Anilina , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/genética , Feminino , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Mutação , Piperazinas/uso terapêuticoRESUMO
BACKGROUND: The population structure of human diarrheagenic Escherichia coli (DEC) isolates derived from worldwide collections remains undefined. METHODS: A total of 1196 clinical isolates were obtained from a multilocus sequence typing (MLST) database. Genetic diversity analysis, MLST analysis, and phylogenetic analysis combined with different pathotypes were performed through a variety of calculation software applications. RESULTS: All isolates were categorized as one of 579 different sequence types (STs). The eBURST algorithm resolved these 579 STs into 27 clonal complexes (CCs), 37 concatemers, and 210 singletons, revealing a high level of genetic diversity in the population structure of DEC. CC10 was the most prevalent CC, comprising 276 (23.08%, 276/1196) isolates with 85 (14.68%, 85/579) STs widely distributed in 20 countries. The population structure of five common pathotypes was highly diversified, and isolates with the same ST or CC were heterogeneous for different pathotypes. Sequence variations were more abundant in fumC and gyrB than in the other five genes, and these exhibited the highest degree of nucleotide diversity (0.03886 and 0.03075, respectively) and the greatest number of polymorphic nucleotide sites (137 and 139, respectively). The dN/dS ratios of seven analyzed loci varied from 0.0083 (recA) to 0.0434 (purA), and the ratio for the concatenated sequence was 0.2518, revealing the effects of purifying selection on housekeeping genes during the evolutionary process. Significant allele linkage disequilibrium was detected when the standardized index of association (ISA) was calculated both for the entire collection of isolates (0.3174, p<0.001) and for the 579 STs (0.1475, p<0.001). CONCLUSIONS: This study facilitated a comprehensive understanding of the genetic diversity of human DEC distributed across the global population. The results provide genetic evidence that will allow us to uncover the microevolutionary relationships among different pathogenic isolates of DEC.