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BACKGROUND AND OBJECTIVE: Nicotine metabolic ratio (NMR) has been associated with nicotine metabolism and smoking characteristics. However, there are few studies on the potential association between NMR and smoking cessation efficacy in smokers with chronic obstructive pulmonary disease (COPD) in China or elsewhere. METHODS: This study was a stratified block randomized controlled trial for smoking cessation in Chinese smokers with COPD. NMR was used as a stratification factor; slow metabolizers were defined as those with NMR <0.31, and normal metabolizers as those with NMR ≥0.31. Participants were randomly assigned to the varenicline or bupropion group. Follow-up visits were conducted at 1, 2, 4, 6, 9, 12 and 24 weeks. RESULTS: Two hundred twenty-four participants were recruited and analysed from February 2019 to June 2022. In normal metabolizers, the 9-12 weeks continuous abstinence rate of varenicline (43.1%) was higher than in bupropion (23.5%) (OR = 2.47, 95% CI 1.05-5.78, p = 0.038). There was no significant difference in abstinence rates between treatment groups in slow metabolizers (54.1% vs. 45.9%, OR = 1.39, 95% CI 0.68-2.83, p = 0.366). For slow metabolizers, the total score of side effects in the varenicline group was significantly higher than the bupropion group (p = 0.048), while there was no significant difference in side effects between groups for normal metabolizers (p = 0.360). CONCLUSION: Varenicline showed better efficacy than bupropion in normal metabolizers, and bupropion showed equivalent efficacy in slow metabolizers with less side effects. According to our study, NMR provides a better justification for both scientific research and tailoring optimal pharmacotherapy for smoking cessation among smokers in COPD.
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Bupropiona , Nicotina , Doença Pulmonar Obstrutiva Crônica , Agentes de Cessação do Hábito de Fumar , Abandono do Hábito de Fumar , Vareniclina , Humanos , Vareniclina/uso terapêutico , Bupropiona/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Masculino , Feminino , Abandono do Hábito de Fumar/métodos , Pessoa de Meia-Idade , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Resultado do Tratamento , Idoso , China/epidemiologia , FumantesRESUMO
BACKGROUNDS: To our knowledge, there is no available nationwide data on omicron symptom patterns in China mainland. We aim to determine the acute and long COVID-19 symptoms in the omicron-dominant period and to evaluate its association with risk factors. METHODS: We designed a cross-sectional nationwide study and data about self-reported symptoms were collected by an online platform named Wenjuanxing. Eligible participants were aged 25-65 years and were symptomatic. In this study, the ratios of the number of people of different ages and genders were weighted by the data from the Seventh National Census (2020 years), and validated by a published nationwide representative study through comparing smoking rates. Descriptive indicators were calculated for demographic characteristics, diagnosis ways, and duration time, acute symptoms, hospitalization, severity and long COVID-19 symptoms. And, the associations between risk factors and acute and long COVID-19 symptoms were analyzed by multivariable logistic regression models. RESULTS: A total of 32,528 individuals diagnosed as COVID-19 infection from October 1, 2022 to February 21, 2023 were included. The first three acute symptoms of COVID-19 infection were fever (69.90%), headache (62.63%), and sore throat (54.29%), respectively. The hospitalization rate within 7 days was 3.07% and symptoms disappearance rate within 21 days was 68.84%, respectively. Among 3983 COVID-19 patients with 3 months or more time difference between first infection and participation into the study, the long COVID-19 rate was 19.68% and the primary symptoms were muscle weakness (19.39%), headache (17.98%) and smell/taste disorder (15.18%). Age groups, smoking, marriage status and vaccination were risk factors for numbers of acute phase symptoms and long COVID-19 symptoms. Lastly, female and current smokers also showed more numbers of symptoms during acute infection period. CONCLUSIONS: In Chinese mainland, our respondent indicated that current smokers and women were associated with acute COVID-19 symptoms, which should be treated with caution due to the lack of representative.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , China/epidemiologia , Adulto , Estudos Transversais , Idoso , Fatores de Risco , Inquéritos e Questionários , Doença AgudaRESUMO
Uncaria rhynchophylla (Gou Teng) and Uncaria tomentosa (cat's claw) are frequently used herbal supplements in Asia and America, respectively. Despite their common usage, information is limited regarding potential herb-drug interactions associated with Gou Teng and cat's claw. The pregnane X receptor (PXR) is a ligand-dependent transcription factor that regulates cytochrome P450 3A4 (CYP3A4) expression and contributes to some known herb-drug interactions. A recent study found that Gou Teng induces CYP3A4 expression, but its mechanism is unknown. Cat's claw has been determined as a PXR-activating herb, but the PXR activators in cat's claw have not been identified. Using a genetically engineered PXR cell line, we found that the extracts of Gou Teng and cat's claw can dose-dependently activate PXR and induce CYP3A4 expression. We next used a metabolomic approach to profile the chemical components in the extracts of Gou Teng and cat's claw followed by screening for PXR activators. Four compounds, isocorynoxeine, rhynchophylline, isorhynchophylline, and corynoxeine, were identified as PXR activators from both Gou Teng and cat's claw extracts. In addition, three more PXR activators were identified from the extracts of cat's claw, including isopteropodine, pteropodine, and mitraphylline. All seven of these compounds showed the half-maximal effective concentration <10 µM for PXR activation. In summary, our work determined Gou Teng as a PXR-activating herb and discovered novel PXR activators from Gou Teng as well as cat's claw. SIGNIFICANCE STATEMENT: This study's data can be used to guide the safe use of Gou Teng and cat's claw by avoiding PXR-mediated herb-drug interactions.
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Unha-de-Gato , Unha-de-Gato/química , Fitoterapia , Citocromo P-450 CYP3A , Receptor de Pregnano X , Extratos Vegetais/farmacologiaRESUMO
BACKGROUND: Randomized controlled trials on text message interventions for smoking cessation have shown they are effective and recommended for tobacco control. However, the effectiveness in real-world settings is largely unknown, especially in low- and middle-income countries. OBJECTIVE: This study aimed to provide real-world evidence about the utilization and effectiveness of a message-based tobacco cessation program (mCessation) in China. METHODS: From May 2021 to September 2022, 16,746 people from the general population participated in the mCessation program provided by the World Health Organization. All participants received text messages on smoking cessation via instant messaging for 6 months, and they were also required to report smoking status. We randomly selected 2500 participants and interviewed them by telephone to determine the 7-day point prevalence abstinence rate at 6 months. Descriptive statistics were used to analyze population characteristics and abstinence rate. Logistic regression analysis was performed to explore risk factors for the abstinence rate. RESULTS: Among the 2500 participants, the mean age was 35 years, and most (2407/2500, 96.20%) were male. The prevalence of tobacco dependence and light degree of tobacco dependence were 85.70% (2142/2500) and 89.10% (2228/2500), respectively. For respondents (953/2500, 38.10%), the 7-day point prevalence abstinence rate at 6 months was 21.90% (209/953). Participants older than 40 years or with tobacco dependence had significantly higher abstinence rates than those who were younger than 30 years old (odds ratio [OR] 1.77, 95% CI 1.06-3.29) or without dependence (OR 1.64, 95% CI 1.08-2.51), respectively. However, married people or heavily dependent smokers tended to find it more difficult to successfully quit smoking compared with unmarried people (OR 0.57, 95% CI 0.34-0.93) or lightly dependent smokers (OR 0.16, 95% CI 0.02-0.98), respectively. CONCLUSIONS: In a real-world setting, mCessation China was generally acceptable to men and lightly dependent smokers, and it could help 1 in 5 smokers aged 18 years to 67 years quit smoking. However, strategies to increase awareness of young and married adults may improve implementation and abstinence rates.
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Abandono do Hábito de Fumar , Envio de Mensagens de Texto , Abandono do Uso de Tabaco , Tabagismo , Adulto , Feminino , Humanos , Masculino , Povo Asiático , População do Leste Asiático , ChinaRESUMO
To exploit high-performance and stable sensing materials with a room working temperature is pivotal for portable and mobile sensor devices. However, the common sensors based on metal oxide semiconductors usually need a higher working temperature (usually above 300 °C) to achieve a good response toward gas detection. Currently, metal halide perovskites have begun to rise as a promising candidate for gas monitoring at room temperature but suffer phase instability. Herein, we construct 1D/3D PyPbI3/FA0.83Cs0.17PbI3 (denoted by PyPbI3/FACs) bilayer perovskite by post-processing spin-coating Pyrrolidinium hydroiodide (PyI) salt on top of 3D FACs film. Benefitting from the 1D PyPbI3 coating layer, the phase stability of 1D/3D PyPbI3/FACs significantly improves. Simultaneously, the gas sensor based on the 1D/3D PyPbI3/FACs bilayer perovskite presents a superior selectivity and sensitivity toward NO2 detection at room temperature, with a low detection limit of 220 ppb. Exposed to a 50 ± 3% relative humidity (RH) level environment for a consecutive six days, the 1D/3D PyPbI3/FACs perovskite-based sensor toward 10 ppm NO2 can still maintain a rapid response with a slight attenuation. Gas sensors based on hybrid 1D/3D-structured perovskite in this work may provide a new pathway for highly sensitive and stable gas sensors in room working temperature, accelerating its practical application and portable device.
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In order to improve the tracking adaptability of autonomous vehicles under different vehicle speeds and road curvature, this paper develops a weight adaptive model prediction control system (AMPC) based on PSO-BP neural network, which consists of a dynamics-based model prediction controller (MPC) and an optimal weight adaptive regulator. Based on the application of MPC to achieve high-precision tracking control, the optimal weight under different operating conditions obtained by automated simulation is used to train the PSO-BP neural network offline to achieve online adjustment of MPC weight. The validation results of the Prescan-Carsim-Simulink joint simulation platform show that the adaptive control system has better tracking adaptation capability compared with the original classical MPC control. The control strategy was also verified on an autonomous vehicle test platform, and the test results showed that the adaptive control strategy improved tracking accuracy while meeting the vehicle's requirements for real-time control and lateral stability.
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Veículos Autônomos , Redes Neurais de Computação , Simulação por Computador , Aclimatação , Modelos BiológicosRESUMO
BACKGROUND: Peripheral hematological changes in severe COVID-19 patients may reflect the immune response during SARS-CoV-2 infection. Characteristics of peripheral white blood cells as early signals were needed to be investigated for clarifying its associations with the fatal outcomes in COVID-19 patients. METHODS: A retrospective cohort study was performed and the hospitalized COVID-19 patients were recruited in wards of Sino-French New City Branch of Tongji Hospital in Wuhan, Hubei province, China. Characteristics of peripheral white blood cells in survivors and non-survivors were analyzed. Comparison among patients with different level of eosinophils was performed. RESULTS: Of 198 patients included in this study, 185 were discharged and 13 died. Levels of eosinophils, lymphocytes and basophils in non-survivors were significantly lower than those in survivors. Death rate in low eosinophils group was higher and no patient died in normal eosinophils group (16.7% vs 0, P < 0.001). The proportion of patients in low eosinophils group who used glucocorticoids was higher than in normal eosinophils group, but glucocorticoids usage was not an indicator for death in subgroup analysis in low eosinophils patients. Moreover, positive correlation was found between the counts of lymphocytes and eosinophils in patients with glucocorticoids use but not in patients without the treatment. CONCLUSIONS: Hematological changes differed between survivors and non-survivors with COVID-19. Lymphopenia and eosinopenia could be predictors for poor prognosis of COVID-19 patients. Initial counts of eosinophils may guide us in usage of glucocorticoids for COVID-19 treatment.
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Tratamento Farmacológico da COVID-19 , China , Humanos , Leucócitos , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that rapidly spreads worldwide and co-infection of COVID-19 and influenza may occur in some cases. We aimed to describe clinical features and outcomes of severe COVID-19 patients with co-infection of influenza virus. METHODS: Retrospective cohort study was performed and a total of 140 patients with severe COVID-19 were enrolled in designated wards of Sino-French New City Branch of Tongji Hospital between Feb 8th and March 15th in Wuhan city, Hubei province, China. The demographic, clinical features, laboratory indices, treatment and outcomes of these patients were collected. RESULTS: Of 140 severe COVID-19 hospitalized patients, including 73 patients (52.14%) with median age 62 years were influenza virus IgM-positive and 67 patients (47.86%) with median age 66 years were influenza virus IgM-negative. 76 (54.4%) of severe COVID-19 patients were males. Chronic comorbidities consisting mainly of hypertension (45.3%), diabetes (15.8%), chronic respiratory disease (7.2%), cardiovascular disease (5.8%), malignancy (4.3%) and chronic kidney disease (2.2%). Clinical features, including fever (≥38 °C), chill, cough, chest pain, dyspnea, diarrhea and fatigue or myalgia were collected. Fatigue or myalgia was less found in COVID-19 patients with IgM-positive (33.3% vs 50/7%, P = 0.0375). Higher proportion of prolonged activated partial thromboplastin time (APTT) > 42 s was observed in COVID-19 patients with influenza virus IgM-negative (43.8% vs 23.6%, P = 0.0127). Severe COVID-19 Patients with influenza virus IgM positive have a higher cumulative survivor rate than that of patients with influenza virus IgM negative (Log-rank P = 0.0308). Considering age is a potential confounding variable, difference in age was adjusted between different influenza virus IgM status groups, the HR was 0.29 (95% CI, 0.081-1.100). Similarly, difference in gender was adjusted as above, the HR was 0.262 (95% CI, 0.072-0.952) in the COX regression model. CONCLUSIONS: Influenza virus IgM positive may be associated with decreasing in-hospital death.
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COVID-19/complicações , Mortalidade Hospitalar , Influenza Humana/complicações , Adulto , Idoso , Anticorpos Antivirais/sangue , China , Coinfecção/virologia , Comorbidade , Feminino , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The catalytic asymmetric synthesis of P-chiral phosphorus compounds is an important way to construct P-chiral ligands. Herein, we report a new strategy that adopts the pyridinyl moiety as the coordinating group in the cobalt-catalysed asymmetric nucleophilic addition/alkylation of secondary phosphine oxides. A series of tertiary phosphine oxides were generated with up to 99 % yield and 99.5 % ee, and with broad functional-group tolerance. Mechanistic studies reveal that (R)-secondary phosphine oxides preferentially interact with the cobalt catalysts to produce P-stereogenic compounds.
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BACKGROUND: Mounting evidence has displayed critical roles of circular RNAs (circRNAs) in multiple cancers. The underlying mechanisms by which circFGD4 contributed to gastric cancer (GC) are still unclear. METHODS: The levels and clinical values of circFGD4 in GC patients were detected and analysed by quantitative real-time PCR. The biological roles of circFGD4 in GC were assessed in vitro and in vivo experiments. Dual-luciferase reporter, fluorescence in situ hybridization, RNA immunoprecipitation, biotin-coupled RNA pull-down, and TOP/Flash and FOP/Flash reporter gene assays were employed to evaluate the effects of circFGD4 on miR-532-3p-mediated adenomatous polyposis coli (APC)/ß-catenin signalling in GC cells. RESULTS: circFGD4 expression was down-regulated the most in human GC tissues and cell lines. Low expression of circFGD4 was correlated with poor tumour differentiation, lymphatic metastasis, and poor prognosis of GC patients. circFGD4 suppressed GC cell viability, colony formation, migration, induced epithelial-mesenchymal transition (EMT), and tumorigenesis and metastasis in vivo. Next, we validated that circFGD4 acted as a sponge of miR-532-3p to relieve the tumour-promoting effects of miR-532-3p on its target APC. The mechanistic analysis demonstrated that the circFGD4 suppressed GC cell viability, migration, and EMT by modulating the miR-532-3p/APC axis to inactivate the ß-catenin signalling. CONCLUSION: circFGD4 suppressed GC progression through sponging miR-532-3p and enhancing APC expression to inactivate the ß-catenin signalling. Thus circFGD4 provides a novel potential biomarker and valuable therapeutic strategy for GC.
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Proteína da Polipose Adenomatosa do Colo/metabolismo , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/genética , RNA Circular/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , beta Catenina/metabolismo , Proteína da Polipose Adenomatosa do Colo/genética , Progressão da Doença , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Proteínas dos Microfilamentos/metabolismo , RNA Circular/metabolismo , Transdução de Sinais , Neoplasias Gástricas/fisiopatologia , beta Catenina/genéticaRESUMO
BACKGROUND: Orolabial herpes simplex virus type 1 (HSV-1) infection has a wide spectrum of severity in immunocompetent persons. To study the role of viral genotype and host immunity, we characterized oral HSV-1 shedding rates and host cellular response, and genotyped viral strains, in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: A total of 29 MZ and 22 DZ HSV-1-seropositive twin pairs were evaluated for oral HSV-1 shedding for 60 days. HSV-1 strains from twins were genotyped as identical or different. CD4+ T-cell responses to HSV-1 proteins were studied. RESULTS: The median per person oral HSV shedding rate was 9% of days that a swab was obtained (mean, 10.2% of days). A positive correlation between shedding rates was observed within all twin pairs, and in the MZ and DZ twins. In twin subsets with sufficient HSV-1 DNA to genotype, 15 had the same strain and 14 had different strains. Viral shedding rates were correlated for those with the same but not different strains. The median number of HSV-1 open reading frames recognized per person was 16. The agreement in the CD4+ T-cell response to specific HSV-1 open reading frames was greater between MZ twins than between unrelated persons (P = .002). CONCLUSION: Viral strain characteristics likely contribute to oral HSV-1 shedding rates.
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Herpes Labial/imunologia , Herpes Labial/virologia , Herpesvirus Humano 1/genética , Eliminação de Partículas Virais/genética , Adulto , Idoso , Linfócitos T CD4-Positivos/imunologia , Feminino , Genótipo , Herpes Labial/classificação , Herpesvirus Humano 1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Boca/virologia , Fases de Leitura Aberta/genética , Fases de Leitura Aberta/imunologia , Filogenia , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto JovemRESUMO
BACKGROUND: Molecular studies have tried to address the unmet need for prognostic biomarkers in prostate cancer (PCa). Some gene expression tests improve upon clinical factors for prediction of outcomes, but additional tools for accurate prediction of tumor aggressiveness are needed. METHODS: Based on a previously published panel of 23 gene transcripts that distinguished patients with metastatic progression, we constructed a prediction model using independent training and testing datasets. Using the validated messenger RNAs and Gleason score (GS), we performed model selection in the training set to define a final locked model to classify patients who developed metastatic-lethal events from those who remained recurrence-free. In an independent testing dataset, we compared our locked model to established clinical prognostic factors and utilized Kaplan-Meier curves and receiver operating characteristic analyses to evaluate the model's performance. RESULTS: Thirteen of 23 previously identified gene transcripts that stratified patients with aggressive PCa were validated in the training dataset. These biomarkers plus GS were used to develop a four-gene (CST2, FBLN1, TNFRSF19, and ZNF704) transcript (4GT) score that was significantly higher in patients who progressed to metastatic-lethal events compared to those without recurrence in the testing dataset (P = 5.7 × 10-11 ). The 4GT score provided higher prediction accuracy (area under the ROC curve [AUC] = 0.76; 95% confidence interval [CI] = 0.69-0.83; partial area under the ROC curve [pAUC] = 0.008) than GS alone (AUC = 0.63; 95% CI = 0.56-0.70; pAUC = 0.002), and it improved risk stratification in subgroups defined by a combination of clinicopathological features (ie, Cancer of the Prostate Risk Assessment-Surgery). CONCLUSION: Our validated 4GT score has prognostic value for metastatic-lethal progression in men treated for localized PCa and warrants further evaluation for its clinical utility.
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Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio/genética , Metástase Neoplásica/genética , Neoplasias da Próstata/genética , Receptores do Fator de Necrose Tumoral/genética , Cistatinas Salivares/genética , Fatores Genéricos de Transcrição/genética , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica/patologia , Prognóstico , Neoplasias da Próstata/patologia , RNA Mensageiro/análise , Curva ROC , Medição de Risco , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Prognostic biomarkers for localized prostate cancer (PCa) could improve personalized medicine. Our group previously identified a panel of differentially methylated CpGs in primary tumor tissue that predict disease aggressiveness, and here we further validate these biomarkers. METHODS: Pyrosequencing was used to assess CpG methylation of eight biomarkers previously identified using the HumanMethylation450 array; CpGs with strongly correlated (r >0.70) results were considered technically validated. Logistic regression incorporating the validated CpGs and Gleason sum was used to define and lock a final model to stratify men with metastatic-lethal versus non-recurrent PCa in a training dataset. Coefficients from the final model were then used to construct a DNA methylation score, which was evaluated by logistic regression and Receiver Operating Characteristic (ROC) curve analyses in an independent testing dataset. RESULTS: Five CpGs were technically validated and all were retained (P < 0.05) in the final model. The 5-CpG and Gleason sum coefficients were used to calculate a methylation score, which was higher in men with metastatic-lethal progression (P = 6.8 × 10-6 ) in the testing dataset. For each unit increase in the score there was a four-fold increase in risk of metastatic-lethal events (odds ratio, OR = 4.0, 95%CI = 1.8-14.3). At 95% specificity, sensitivity was 74% for the score compared to 53% for Gleason sum alone. The score demonstrated better prediction performance (AUC = 0.91; pAUC = 0.037) compared to Gleason sum alone (AUC = 0.87; pAUC = 0.025). CONCLUSIONS: The DNA methylation score improved upon Gleason sum for predicting metastatic-lethal progression and holds promise for risk stratification of men with aggressive tumors. This prognostic score warrants further evaluation as a tool for improving patient outcomes.
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Herpes simplex virus (HSV) infection is restricted to epithelial cells and neurons and is controlled by CD8 T cells. These cells both traffic to epithelial sites of recurrent lytic infection and to ganglia and persist at the dermal-epidermal junction for up to 12 weeks after lesion resolution. We previously showed that cutaneous lymphocyte-associated antigen (CLA), a functional E-selectin ligand (ESL), is selectively expressed on circulating HSV-2-specific CD8 T cells. CLA/ESL mediates adhesion of T cells to inflamed vascular endothelium. Later stages in T-cell homing involve chemokines (Ch) and lymphocyte chemokine receptors (ChR) for vascular wall arrest and diapedesis. Several candidate ChR have been implicated in skin homing. We measured cell surface ChR on HSV-specific human peripheral blood CD8 T cells and extended our studies to HSV-1. We observed preferential cell surface expression of CCR10 and CXCR3 by HSV-specific CD8 T cells compared to CD8 T cells specific for control viruses, Epstein-Barr virus (EBV) and cytomegalovirus (CMV), and compared to bulk memory CD8 T cells. CXCR3 ligand mRNA levels were selectively increased in skin biopsy specimens from persons with recurrent HSV-2, while the mRNA levels of the CCR10 ligand CCL27 were equivalent in lesion and control skin. Our data are consistent with a model in which CCL27 drives baseline recruitment of HSV-specific CD8 T cells expressing CCR10, while interferon-responsive CXCR3 ligands recruit additional cells in response to virus-driven inflammation.IMPORTANCE HSV-2 causes very localized recurrent infections in the skin and genital mucosa. Virus-specific CD8 T cells home to the site of recurrent infection and participate in viral clearance. The exit of T cells from the blood involves the use of chemokine receptors on the T-cell surface and chemokines that are present in infected tissue. In this study, circulating HSV-2-specific CD8 T cells were identified using specific fluorescent tetramer reagents, and their expression of several candidate skin-homing-associated chemokine receptors was measured using flow cytometry. We found that two chemokine receptors, CXCR3 and CCR10, are upregulated on HSV-specific CD8 T cells in blood. The chemokines corresponding to these receptors are also expressed in infected tissues. Vaccine strategies to prime CD8 T cells to home to HSV lesions should elicit these chemokine receptors if possible to increase the homing of vaccine-primed cells to sites of infection.
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Linfócitos T CD8-Positivos/imunologia , Quimiocina CCL27/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 2/imunologia , Ativação Linfocitária/imunologia , Receptores CCR10/imunologia , Receptores CXCR3/imunologia , Antígenos de Diferenciação de Linfócitos T/imunologia , Linfócitos T CD8-Positivos/metabolismo , Quimiocina CCL27/genética , Citomegalovirus/imunologia , Feminino , Citometria de Fluxo , Herpes Simples/virologia , Herpesvirus Humano 4/imunologia , Humanos , Memória Imunológica/imunologia , Masculino , Glicoproteínas de Membrana/imunologia , RNA Mensageiro/genética , Receptores CCR10/biossíntese , Receptores CCR10/genética , Receptores CXCR3/biossíntese , Receptores CXCR3/genética , Pele/virologiaRESUMO
BACKGROUND: Recently awareness of the importance of Aspergillus colonization in the airway of patients with chronic obstructive pulmonary disease (COPD) was rising. The aim of this study was to investigate the clinical features and short-term outcomes of COPD patients with Aspergillus colonization during acute exacerbation. METHODS: A pair-matched retrospective study on patients presenting with COPD exacerbation was conducted from January 2014 to March 2016 in Beijing Hospital, China. RESULTS: Twenty-three patients with Aspergillus colonization and 69 patients as controls, diagnosed of COPD exacerbation, were included in this study at a pair-matched ratio of 1:3. In stable stage, the percentage of patients with high-dose corticosteroids inhalation in the Aspergillus colonization group is higher than that of in control group (65.5% vs 33.3%, p = 0.048). Multivariate analysis showed that corticosteroids use was the risk factor for isolation of Aspergillus. In acute exacerbation stage, patients in Aspergillus colonization group received higher dose of inhaled corticosteroids and more types of antibiotics than control group. The short-time outcome hinted that the remission time and the duration of hospitalization were longer in the Aspergillus colonization group than in the control group (remission time: 11 ± 4 days vs 7 ± 4 days, p = 0.001; duration: 15 ± 5 days vs 12 ± 4 days, p = 0.011). CONCLUSIONS: Aspergillus colonization in the lower respiratory tract of COPD patients showed typical clinical manifestations, affected their short time outcome and provided a dilemma of clinical treatment strategy.
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Antibacterianos , Aspergillus fumigatus , Glucocorticoides , Aspergilose Pulmonar , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/classificação , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/isolamento & purificação , China/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/microbiologia , Estudos Retrospectivos , Fatores de Risco , Exacerbação dos SintomasRESUMO
BACKGROUND/AIMS: Human leukocyte antigen-G (HLA-G) plays an important role in inhibiting natural killer (NK) cell function and promoting immune escape. However, the specific mechanism of HLA-G on NK in gastric cancer (GC) remains not well understood. This study investigated the expression of HLA-G in GC and the role of HLA-G-effected NK cells in GC progression. METHODS: HLA-G expression in GC tissues obtained from 49 patients with GC was analyzed by immunohistochemistry and western blot. The number of tumor-infiltrating NK cells and the expression of their surface receptors were analyzed by immunohistochemistry and flow cytometry, respectively. The effect of HLA-G on NK cell proliferation was examined by Cell Counting Kit-8 (CCK8) assay. LDH release assay was used to evaluate the effect of HLA-G on the cytotoxic activity of NK cells, and the levels of IFN-γ and TNF-α in the co-cultured supernatant were detected by ELISA. Mice bearing a xenograft tumor model were used to examine the effect of HLA-G on the anti-tumor effect of NK cells. RESULTS: HLA-G positive expression was detected in most of the GC tissues, and was correlated with the adverse prognosis of the disease. The expression of HLA-G was negatively associated with the number of tumor-infiltrating NK cells. Furthermore, GC cell lines with overexpressed HLA-G revealed their ability to inhibit the cell proliferation and cytotoxic activity of NK-92MI cells, and reduce the secretion of IFN-γ and TNF-α through immunoglobulin-like transcript 2 (ILT2). Finally, this in vivo experiment was able to prove that HLA-G can inhibit the anti-tumor effect of NK cells through ILT2. CONCLUSION: The expression of HLA-G was strongly correlated with the adverse prognosis of GC. The reason may be that it inhibits the proliferation and cytotoxic activity of infiltrating NK cells through ILT2.
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Antígenos CD/metabolismo , Antígenos HLA-G/metabolismo , Células Matadoras Naturais/imunologia , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/metabolismo , Neoplasias Gástricas/patologia , Idoso , Animais , Antígenos CD/genética , Linhagem Celular Tumoral , Proliferação de Células , Técnicas de Cocultura , Intervalo Livre de Doença , Feminino , Antígenos HLA-G/genética , Humanos , Interferon gama/análise , Interferon gama/metabolismo , Células Matadoras Naturais/metabolismo , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/genética , Ativação Linfocitária/imunologia , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Prognóstico , Receptores KIR2DL4/genética , Receptores KIR2DL4/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Transplante Heterólogo , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Herpes simplex virus type 2 (HSV-2) reactivation is accompanied by a sustained influx of CD4(+) and CD8(+) T cells that persist in genital tissue for extended periods. While CD4(+) T cells have long been recognized as being present in herpetic ulcerations, their role in subclinical reactivation and persistence is less well known, especially the role of CD4(+) regulatory T cells (Tregs). METHODS: We characterized the Treg (CD4(+)Foxp3(+)) population during human HSV-2 reactivation in situ in sequential genital skin biopsy specimens obtained from HSV-2-seropositive subjects at the time of lesion onset up to 8 weeks after healing. RESULTS: High numbers of Tregs infiltrated to the site of viral reactivation and persisted in proximity to conventional CD4(+) T cells (Tconvs) and CD8(+) T cells. Treg density peaked during the lesion stage of the reactivation. The number of Tregs from all time points (lesion, healed, 2 weeks after healing, 4 weeks after healing, and 8 weeks after healing) was significantly higher than in control biopsy specimens from unaffected skin. There was a direct correlation between HSV-2 titer and Treg density. CONCLUSIONS: The association of a high Treg to Tconv ratio with high viral shedding suggests that the balance between regulatory and effector T cells influences human HSV-2 disease.
Assuntos
Genitália/inervação , Genitália/virologia , Herpes Genital/fisiopatologia , Herpesvirus Humano 2/fisiologia , Linfócitos T Reguladores/virologia , Ativação Viral/fisiologia , Eliminação de Partículas Virais/fisiologia , Feminino , Humanos , Masculino , WashingtonRESUMO
Human cytomegalovirus (CMV) has historically been the major infectious cause of morbidity and mortality among patients receiving hematopoietic cell or organ transplant. Standard care in a transplant setting involves frequent monitoring of CMV viral load over weeks to months to determine when antiviral treatment may be required. Quantitative PCR (qPCR) is the standard molecular diagnostic method for monitoring. Recently, digital PCR (dPCR) has shown promise in viral diagnostics, although current dPCR systems have lower throughput than qPCR systems. Here, we compare qPCR and droplet digital PCR (ddPCR) for CMV detection in patient plasma samples. Droplet digital PCR exhibits increased precision over qPCR at viral loads of ≥4 log10 with equivalent sensitivity. However, retrospective analysis of longitudinal samples from transplant patients with CMV viral loads near therapeutic thresholds did not provide evidence that the improved precision of ddPCR would be of clinical benefit. Given the throughput advantages of current qPCR systems, a widespread switch to dPCR for CMV monitoring would appear premature.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Infecções por Citomegalovirus/virologia , Humanos , Plasma/virologia , Transplantados , Carga Viral/métodosRESUMO
PURPOSE: Inspiratory muscle training (IMT) has emerged as a potential intervention to improve respiratory outcomes for patients undergoing cardiac surgery. However, the extent of the IMT effects on preoperative and postoperative respiratory metrics remains uncertain. Hence, we designed this study to determine the effects of IMT on various outcomes of patients undergoing cardiac surgery. METHODS: We conducted a comprehensive meta-analysis of studies evaluating the impact of preoperative and postoperative IMT on various respiratory variables and postsurgical outcomes. We synthesized data from multiple studies, encompassing diverse patient populations and IMT protocols. The key outcomes included the maximal inspiratory pressure (MIP), forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and others. RESULTS: Our meta-analysis results showed that preoperative IMT significantly improved the MIP values with a pooled standard mean difference (SMD) of 0.62. The hospital stay length was also reduced with a SMD of - 0.4. Other variables such as FEV1 and FVC also improved significantly. Postoperative IMT improved the MIP and peak flow rate values, but the evidence was less robust than with preoperative interventions. We observed high heterogeneity across studies for several outcomes and found evidence of publication bias for some postoperative measures. CONCLUSION: Both preoperative and postoperative IMT offer benefits for patients undergoing operations, especially by enhancing respiratory muscle strength and potentially reducing hospital stays. However, the presence of heterogeneity and publication bias underscores the need for further standardized research to consolidate these findings and standardize IMT protocols for optimal patient outcomes.
RESUMO
What is already known about this topic?: Medication non-adherence significantly impedes smoking cessation efforts. While effective smoking cessation medications are accessible in China, real-world adherence and its correlation with treatment outcomes remain largely unexplored. What is added by this report?: From December 2017 to January 2022, 1,120 participants were recruited from 27 centers in all seven geographical regions of China. Results revealed that only 38.2% of smokers adhered to the prescribed 12-week smoking cessation treatment and those with a higher education level were more likely to be adherent. In addition, smokers with good adherence were more likely to successfully quit smoking. What are the implications for public health practice?: The data obtained could enhance our understanding of smoking cessation practices in China. Improving adherence is a crucial strategy to enhance the effectiveness of smoking cessation treatments and management provided to smokers.