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1.
Ther Adv Med Oncol ; 14: 17588359221096214, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547095

RESUMO

The general immune landscape of nasopharyngeal carcinoma (NPC) renders immunotherapy suitable for patients with NPC. Immune checkpoint inhibitors (ICIs) based on programmed death-1/programmed death ligand-1 (PD-1/PD-L1) blockade have made a breakthrough with the approval of PD-1 inhibitor for refractory recurrence and/or metastatic (R/M NPC) and the approval of PD-1 inhibitor in combination with gemcitabine and cisplatin as first line for R/M NPC in 2021 in China. The incorporation of ICIs into the treatment paradigms of NPC has become a clinical hot spot and many prospective clinical studies are ongoing. In this review, we provide a comprehensive overview of the rationale for immunotherapy in NPC and current status, advances and challenges of immunotherapy in NPC based on published clinical data, and ongoing trials. We focus on the clinical application and advances of PD-1 inhibitor monotherapy and its combination with chemotherapy and summarize the clinical explorations of other immunotherapy approaches, for example, combination of PD-1/PD-L1 inhibitors with antiangiogenic inhibitor with molecular targeted agents, cancer vaccines, adaptive immunotherapy, and new ICI agents beyond PD-1/PD-L1 inhibitors in R/M NPC. We also describe the clinical studies' status and challenges of ICIs-based immunomodulatory strategies in local advanced NPC and pay attention to the biomarker application for personalized immunotherapy of NPC in the hope to provide insights for clinical practice and future clinical studies.

2.
Clin Med Insights Oncol ; 16: 11795549221090186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509769

RESUMO

Background: Pancreatic acinar cell carcinoma (PACC) is rare, and its appropriate treatment remains unknown. We aim to explore the characteristics and optimal treatment of it. Methods: The data on clinicopathologic characteristics, molecular alteration, treatment, and survival of patients diagnosed with PACC at the Sun Yat-sen University Cancer Center from 2005 to 2020 were collected. The optimal treatment was explored by co-analyzing our results and published literatures. Results: Twenty-two PACC patients were enrolled. Eight of 17 non-metastatic patients received adjuvant chemotherapy. The patients receiving fluoropyrimidine-based regimen (n = 3) had a better median disease-free survival (mDFS) than those with gemcitabine-based regimen (n = 5) (unreached vs 27 months). Eight metastatic patients received first-line chemotherapy. Four patients received second-line chemotherapy. The objective response rate (ORR) of the fluoropyrimidine-based regimen was 85.7% (6/7), much better than that of the gemcitabine-based regimen (0/5). One patient who had responded to the first-line FOLFIRINOX (5-fluorouracil + oxaliplatin + leucovorin + irinotecan) regimen received olaparib as maintenance treatment for 5 months with good tolerance. Thirty-one published literatures, with a total of 86 cases, were included in the co-analysis. The ORR of the first-line fluoropyrimidine-based regimen (n = 47) was higher than that of gemcitabine-based regimen (n = 39) (59.6% vs 15.3%, P < .001). Eight of 11 patients treated with the FOLFIRINOX regimen achieved partial response (PR). Conclusions: For patients with metastasis, a fluorouracil-based regimen such as FOLFIRINOX may be preferred, and maintenance treatment of poly ADP-ribose polymerase (PARP) inhibitors after effective platinum-containing treatment for breast cancer susceptibility gene (BRCA) mutation patients must be assessed.

3.
COPD ; 19(1): 118-124, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35385369

RESUMO

OBJECTIVE: We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. METHODS: Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. RESULTS: After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 - 0.71); specificity 0.72 (0.71 - 0.73), PPV 0.25 (0.24 - 0.26) and NPV 0.94 (0.94 - 0.95). CONCLUSION: We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504 .


Assuntos
Doença Pulmonar Obstrutiva Crônica , Adulto , Área Sob a Curva , China/epidemiologia , Estudos Epidemiológicos , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Curva ROC , Espirometria , Inquéritos e Questionários
4.
JAMA Netw Open ; 5(3): e220587, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35230439

RESUMO

IMPORTANCE: Anti-programmed cell death 1 (anti-PD-1) immunotherapy features a durable response and improved survival in a small subset of patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). The association between plasma Epstein-Barr virus (EBV) DNA titer dynamics and efficacy of anti-PD-1 monotherapy has been reported, while its value in predicting long-term outcomes and monitoring disease progression is unclear for patients with RM-NPC who are receiving anti-PD-1 monotherapy. OBJECTIVE: To evaluate the role of plasma EBV DNA titers in prognosis prediction and surveillance of disease progression for patients with RM-NPC who are receiving anti-PD-1 monotherapy. DESIGN, SETTING, AND PARTICIPANTS: Patients with RM-NPC from the POLARIS-02 prospective clinical trial, the largest cohort to receive anti-PD-1 monotherapy, were included in this study. From December 22, 2016, to February 19, 2019, 17 participating centers in China screened 279 patients with RM-NPC; 190 patients were enrolled and followed up until February 19, 2020. Plasma EBV DNA was detected before treatment and every 4 weeks until disease progression. MAIN OUTCOMES AND MEASURES: Plasma EBV DNA as a predictor for progression-free survival (PFS), overall survival (OS), durable clinical benefit (defined as PFS of ≥6 months), and disease progression. RESULTS: Of 179 patients with RM-NPC receiving anti-PD-1 therapy, 148 (82.7%) were men, and the median age was 46 years (range, 22-71 years). A higher baseline EBV DNA titer was associated with shorter median OS (hazard ratio, 1.88; 95% CI, 1.22-2.89; P = .004). Patients with a ratio of the EBV DNA titer at week 4 to that at baseline (W4 to baseline ratio) greater than 0.5 had shorter median OS (hazard ratio, 2.18; 95% CI, 1.30-3.65; P < .001) than those with a W4 to baseline ratio of 0.5 or less. Patients with higher baseline EBV DNA titers had a lower durable clinical benefit rate than those with lower baseline EBV DNA titers (19 of 97 [19.6%] vs 27 of 71 [38.0%]; P = .01). Similarly, patients with a W4 to baseline ratio greater than 0.5 had a lower durable clinical benefit rate than those with a W4 to baseline ratio of 0.5 or less (9 of 86 [10.5%] vs 32 of 54 [59.3%]; P < .001). In addition, a significant EBV DNA titer increase was present at a median of 2.6 months (IQR, 0.9-4.5 months) prior to radiographic progression. CONCLUSIONS AND RELEVANCE: This study of plasma EBV DNA in patients with RM-NPC who are receiving anti-PD-1 monotherapy suggests that plasma EBV DNA could be a useful biomarker for outcomes and monitoring disease progression.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Adulto , Idoso , DNA Viral , Progressão da Doença , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/patologia , Feminino , Herpesvirus Humano 4/genética , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Recidiva Local de Neoplasia , Estudos Prospectivos , Adulto Jovem
5.
Environ Res ; 209: 112877, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35131324

RESUMO

BACKGROUND: Studies on the association of greenness with respiratory health are scarce in developing countries, and previous studies in China have focused on only one or two indicators of lung function. OBJECTIVE: The study aims to evaluate the associations of residential greenness with full-spectrum lung function indicators and prevalence of chronic obstructive pulmonary disease (COPD). METHODS: This nationwide cross-sectional survey included 50,991 participants from the China Pulmonary Health study. Lung function indicators included four categories: indicators of obstructive ventilatory dysfunction (FEV1, FVC and FEV1/FVC); an indicator of large-airway dysfunction (PEF); indicators of small-airway dysfunction (FEF25-75% and FEV3/FEV6); and other indicators. Residential greenness was assessed by the Normalized Difference Vegetation Index (NDVI). Multivariable linear regression models and logistic regression models were used to analyze associations of greenness with lung function and COPD prevalence. RESULTS: Within the 500 m buffer, an interquartile range (IQR) increase in NDVI was associated with higher FEV1 (24.76 mL), FVC (16.52 mL), FEV1/FVC (0.38), FEF50% (56.34 mL/s), FEF75% (33.43 mL/s), FEF25-75% (60.73 mL/s), FEV3 (18.59 mL), and FEV6 (21.85 mL). However, NDVI was associated with lower PEF. In addition, NDVI was significantly associated with 10% lower odds of COPD. The stratified analyses found that the associations were only significant in middle-young people, females, and nonsmokers. The associations were influenced by geographic regions. CONCLUSIONS: Residential greenness was associated with better lung function and lower odds of COPD in China. These findings provide a scientific basis for healthy community planning.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Adolescente , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Testes de Função Respiratória
6.
Allergy Asthma Immunol Res ; 14(1): 85-98, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34983109

RESUMO

PURPOSE: As stated in the Global Initiative for Asthma, there are still some asthmatic patients who have not achieved asthma control. Mobile is a useful tool for asthma management. We aimed to compare the advantages of mobile management with traditional management in improving adherence and control of asthma. METHODS: In this prospective, multicentre, randomized, controlled and parallel-group study, we enrolled patients with poor adherence and uncontrolled asthma at 32 hospitals in 28 provinces in China. Patients were randomly assigned to the mobile management or traditional management groups for 12 months. The primary endpoint was the proportion of patients with good adherence (Medication Adherence Report Scale for Asthma [MARS-A] score ≥ 45) for 6 months. This study is registered at ClinicalTrials.gov (NCT02917174). RESULTS: Between April 2017 and April 2018, 923 patients were eligible for randomization (mobile group, n = 461; traditional group, n = 462). Dropout was 84 (18.2%) in the mobile management group and 113 (24.4%) patients in the traditional management group. The proportion of patients with good adherence was significantly higher in the mobile management group than in the traditional management group (66.0% vs. 58.99%, P = 0.048). The mobile management group showed higher mean MARS-A score (at 1, 6, 9, and 12 months) and asthma control test scores (at 6 and 9 months), and lower total lost rate to follow-up within 12 months than the traditional management group. CONCLUSIONS: Mobile asthma management can improve adherence and asthma control compared to traditional management. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02917174.

7.
Am J Respir Crit Care Med ; 205(4): 450-458, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34813411

RESUMO

Rationale: It remains unknown whether long-term ozone exposure can impair lung function. Objectives: To investigate the associations between long-term ozone exposure and adult lung function in China. Methods: Lung function results and diagnosis of small airway dysfunction (SAD) were collected from a cross-sectional study, the China Pulmonary Health Study (N = 50,991). We used multivariable linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trends. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD). Measurements and Main Results: We observed that each 1 SD (4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 ml/s (95% confidence interval [CI], 8.8-19.6 ml/s] decrease in forced expiratory flow at the 75th percentile of vital capacity and a 29.5 ml/s (95% CI, 19.6-39.5 ml/s) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI, 1.06-1.11) for a 1 SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with decreased FEV1/FVC but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group. Conclusions: We found independent associations of long-term ozone exposure with impaired small airway function and higher SAD risks, while the associations with airflow obstruction were weak. Patients with COPD appear to be more vulnerable.


Assuntos
Poluentes Atmosféricos/toxicidade , Exposição Ambiental/efeitos adversos , Pulmão/fisiopatologia , Ozônio/toxicidade , Adulto , Idoso , China , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória
8.
BMC Cancer ; 22(1): 273, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35291981

RESUMO

BACKGROUND: Associations of High-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol (CHL), and triglyceride (TRG) concentrations with risk of biliary tract cancer (BtC) were conflicting in observational studies. We aim to investigate the causal link between circulating lipids and BtC using genetic information. METHODS: Single nucleotide polymorphisms of the four circulating lipids (n = 34,421) and BtC (418 cases and 159,201 controls) were retrieved from two independent GWAS studies performed in East Asian populations. Two-sample univariate and multivariate Mendelian Randomization (MR) analyses were conducted to determine the causal link between circulating lipids and BtC. RESULTS: No significant horizontal pleiotropy was detected for all circulating lipids according to the MR-PRESSO global test (P = 0.458, 0.368, 0.522, and 0.587 for HDL, LDL, CHL, and TRG, respectively). No significant evidence of heterogeneity and directional pleiotropy was detected by the Cochran's Q test and MR-Egger regression. Univariate MR estimates from inverse variance weighting method suggested that one standard deviation (1-SD) increase of inverse-normal transformed HDL (OR = 1.38, 95% CI 0.98-1.94), LDL (OR = 1.46, 95% CI 0.96-2.23), and CHL (OR = 1.34, 95% CI 0.83-2.16) were not significantly associated with BtC risk. Whereas 1-SD increase of inverse-normal transformed TRG showed a significantly negative association with BtC risk (OR = 0.48, 95% CI 0.31-0.74). In multivariate MR analyses including all the four lipid traits, we found that 1-SD increase of LDL and TRG was significantly associated with elevated (OR = 1.32, 95% CI 1.04-2.01) and decreased (OR = 0.54, 95% CI 0.42-0.68) risk of BtC, respectively. CONCLUSION: Circulating lipids, particularly LDL and TRG, may have roles in the development of BtC. However, the results of this study should be replicated in MR with larger GWAS sample sizes for BtC.


Assuntos
Neoplasias do Sistema Biliar , Análise da Randomização Mendeliana , /genética , Neoplasias do Sistema Biliar/epidemiologia , Neoplasias do Sistema Biliar/genética , HDL-Colesterol/genética , Humanos , Polimorfismo de Nucleotídeo Único
9.
Front Oncol ; 11: 712760, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900669

RESUMO

BACKGROUND: The clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival. METHODS: Patients who were diagnosed with GC at the three big cancer centers in China from 2015 to 2020 were evaluated retrospectively. MMR/MSI status was assessed using immunohistochemistry/PCR. Clinical and pathological data were collected from the medical record system. RESULTS: A total of 196 patients with dMMR/MSI-H status were enrolled for analysis. The prevalence of MSI-H/dMMR in GC was 6.6%. Another 694 proficient MMR (pMMR) GC patients were enrolled for comparison. Compared with pMMR patients, dMMR/MSI-H patients were associated with older age, female predominance, distal location in the stomach, earlier TNM stage, intestinal subtype, better differentiation, and more negative HER2 status. The median overall survival (OS) of the dMMR/MSI-H group was better than that of the pMMR/microsatellite stability (MSS) group (not reached vs. 53.9 months, p = 0.014). Adjuvant chemotherapy had no impact in both disease-free survival (DFS) and OS of dMMR/MSI-H patients (p = 0.135 and 0.818, respectively). dMMR/MSI-H patients had poorer response and progression-free survival (PFS) of first-line chemotherapy, though they were statistically significant (p = 0.361 and 0.124, respectively). CONCLUSIONS: dMMR/MSI-H GC patients have specific clinicopathological characteristics and better prognosis than pMMR patients.

10.
Int J Chron Obstruct Pulmon Dis ; 16: 3387-3396, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34949919

RESUMO

PURPOSE: Anxiety and depression are often underdiagnosed and affect the prognosis of patients with chronic obstructive pulmonary disease (COPD). We analyzed data from the China Pulmonary Health (CPH) study to assess the prevalence of anxiety and depression in COPD patients and their relationship with disease severity. PATIENTS AND METHODS: A total of 57,779 subjects aged 20 years or older were recruited in the CPH study. All participants were assessed using a standard questionnaire and underwent pulmonary function tests before and after the use of a bronchodilator in local health centers. The Hospital Anxiety and Depression Scale (HADS) questionnaire with a cutoff score of 8 was used to define anxiety and depression. The prevalence of anxiety and depression in patients of COPD were investigated. Multivariate logistic regression was used to investigate the effects of COPD and lung function on anxiety and depression. RESULTS: A total of 49,053 participants (20,661 men and 28,392 women) completed the questionnaire with reliable post-bronchodilator pulmonary function test results and were included in the final analysis, of which 4686 (9.55%) were diagnosed with COPD. Of the patients with COPD, 10.79% had anxiety, 13.65% had depression, and 7.08% had anxiety and depression concomitantly. In the multivariate logistic regression analysis, COPD was not significantly associated with anxiety, depression, or both. After adjusting for confounders in model 1, patients in the GOLD III-IV group had a significantly higher risk of anxiety, depression, and their coincidence. After further adjusting for respiratory symptoms in model 2, lung function impairment in the GOLD III-IV group was only significantly associated with a higher risk of depression or at least one of anxiety and depression. CONCLUSION: Anxiety and depression are prevalent in patients with COPD in China. More severe lung function impairment is significantly associated with a higher risk of depression.


Assuntos
Depressão , Doença Pulmonar Obstrutiva Crônica , Adulto , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Broncodilatadores/uso terapêutico , China/epidemiologia , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Feminino , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Qualidade de Vida , Inquéritos e Questionários , Adulto Jovem
11.
Environ Int ; 156: 106707, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34182192

RESUMO

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 µm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25-75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 µg/m3 to 92 µg/m3 (average: 53 µg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30-28.33), FVC (17.45 mL, 95% CI: 7.16-27.74), PEF (86.64 mL/s, 95% CI: 59.77-113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64-47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China , Estudos Transversais , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Volume Expiratório Forçado , Humanos , Pulmão , Material Particulado/análise
12.
Ther Adv Med Oncol ; 13: 1758835921988996, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613701

RESUMO

BACKGROUND: We previously reported tumor mutation burden (TMB) as a potential prognostic factor for patients with advanced gastric cancer (AGC) receiving immunotherapy. We aimed to comprehensively understand the impact of tumor burden and TMB on efficacy and prognosis in immunotherapy-treated AGC patients. METHODS: A total of 58 patients with refractory AGC receiving PD-1 inhibitor monotherapy from a phase Ib/II clinical trial (ClinicalTrials.gov identifier: NCT02915432) were retrospectively included. Univariate and multivariate logistical regression analyses and the Cox proportional hazards model were performed for prognostic value of baseline factors. Factors reflecting baseline tumor burden, including baseline lesion number (BLN), the maximum tumor size (MTS) and the sum of target lesion size (SLS) were analyzed. The objective response rate (ORR) and disease control rate (DCR) were compared by Chi-square test. RESULTS: In univariate analysis, high BLN was associated with poor median progression-free survival (mPFS) [1.7 months versus 3.4 months; hazard ratio (HR), 2.696, p < 0.05] and median overall survival (mOS) (3.2 months versus 7.6 months; HR, 1.997, p < 0.05), while high TMB was a positive prognostic factor. In multivariable analysis, both BLN and TMB were independent prognostic factors for mOS (BLN: HR, 2.782, p < 0.05; TMB: HR, 0.288, p < 0.05), while MTS or SLS had no association with survival. Better ORR and DCR were observed in the low BLN group (15.4% versus 5.3%, p > 0.05; 86.96% versus 54.29%, p < 0.05). When combining BLN and TMB, the best efficacy and survival were observed in the BLNlowTMBhigh group (ORR: 37.5%, DCR: 62.5%, mPFS and mOS: not reached). The worst efficacy and survival were shown in the BNLhighTMBlow group [ORR: 0% (0/15); DCR: 13.3%; mPFS: 1.7 months; mOS: 2.7 months (all p < 0.05)]. CONCLUSIONS: BLN, rather than factors regarding baseline tumor size, is perhaps a potential predictor for benefit from immunotherapy and its combination with TMB could further risk-stratify patients with AGC receiving immunotherapy.

13.
PLoS One ; 16(1): e0245810, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33493155

RESUMO

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a global problem with high mortality. Its pathogenesis is not fully understood. To reveal new serum feature of AECOPD and their potential implications, we have analyzed 180 serum samples, and found that in the serum of AECOPD patients, 4-hydroxy-2-nonenal (4HNE)-protein adducts are dynamically increased as partial pressure of oxygen (PaO2) drops, which is accompanied by progressively decreasing thioredoxin reductase (TrxR1) and thioredoxin (Trx1), as compared with those of healthy people. This phenomenon is unique, because acute hypoxia patients have 1.1-fold or 1.7-fold higher serum TrxR1 or Trx1 activity, respectively, than healthy people, in keeping with low 4HNE level. Moreover, serum 4HNE-protein adducts may form disulfide-linked complexes with high-molecular-weight, the amount of which is significantly increased during AECOPD. Serum 4HNE-protein adducts include 4HNE-Trx1 adduct and 4HNE-TrxR1 adduct, but only the former is significantly increased during AECOPD. Through cell biology, biochemistry and proteomics methods, we have demonstrated that extracellular 4HNE and 4HNE-Trx1 adduct affect human bronchial epithelial cells via different mechanisms. 4HNE-Trx1 adduct may significantly alter the expression of proteins involved mainly in RNA metabolism, but it has no effect on TrxR1/Trx1 expression and cell viability. On the other hand, low levels of 4HNE promote TrxR1/Trx1 expression and cell viability, while high levels of 4HNE inhibit TrxR1/Trx1 expression and cell viability, during which Trx1, at least in part, mediate the 4HNE action. Our data suggest that increasing serum 4HNE and decreasing serum Trx1 in AECOPD patients are closely related to the pathological processes of the disease. This finding also provides a new basis for AECOPD patients to use antioxidant drugs.


Assuntos
Aldeídos/sangue , Células Epiteliais/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Tiorredoxinas/sangue , Idoso , Estudos de Casos e Controles , Sobrevivência Celular , Feminino , Glutationa/metabolismo , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/sangue , Espécies Reativas de Oxigênio/metabolismo
14.
Addict Biol ; 26(2): e12888, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32115811

RESUMO

The gray matter volume (GMV) of the putamen has been reported to be regulated by kinectin 1 gene (KTN1). As a hub of the dopaminergic circuit, the putamen is widely implicated in the etiological processes of substance use disorders (SUD). Here, we aimed to identify robust and reliable associations between KTN1 SNPs and SUD across multiple samples. We examined the associations between SUD and KTN1 SNPs in four independent population-based or family-based samples (n = 10,209). The potential regulatory effects of the risk alleles on the putamen GMVs, the effects of alcohol, nicotine, marijuana and cocaine on KTN1 mRNA expression, and the relationship between KTN1 mRNA expression and SUD were explored. We found that a total of 23 SNPs were associated with SUD across at least two independent samples (1.4 × 10-4 ≤ p ≤ 0.049), including one SNP (rs12895072) across three samples (8.8 × 10-3 ≤ p ≤ 0.049). Four other SNPs were significantly or suggestively associated with SUD only in European-Australians (4.8 × 10-4 ≤ p ≤ 0.058). All of the SUD-risk alleles of these 27 SNPs increased (ß > 0) the putamen GMVs and represented major alleles (f > 0.5) in Europeans. Twenty-two SNPs were potentially biologically functional. Alcohol, nicotine and cocaine significantly affected the KTN1 mRNA expression, and the KTN1 mRNA was differentially expressed between nicotine or cocaine dependent and control subjects. We concluded that there was a replicable and robust relationship among the KTN1 variants, KTN1 mRNA expression, putamen GMVs, molecular effects of substances, and SUD, suggesting that some risk KTN1 alleles might increase kinectin 1 expression in the putamen, altering putamen structures and functions, and leading to SUD.


Assuntos
Proteínas de Membrana/genética , Putamen/patologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/genética , Alcoolismo/epidemiologia , Alcoolismo/genética , Alelos , Austrália , Comorbidade , Feminino , Predisposição Genética para Doença , Substância Cinzenta/patologia , Humanos , Masculino , Abuso de Maconha/epidemiologia , Abuso de Maconha/genética , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/biossíntese , Tabagismo/epidemiologia , Tabagismo/genética
15.
Cell Biochem Funct ; 39(1): 139-147, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33164256

RESUMO

Many studies have shown that adiponectin is closely related to chronic obstructive pulmonary disease (COPD), but the specific role of adiponectin in COPD is still not well understood. Adiponectin and IL-6 expression in patients with acute exacerbation of COPD (AECOPD) was detected by ELISA. Human bronchial epithelial cells (HBECs) were stimulated with TNF-α, IL-6, apoptotic cells or LPS. Then, the expression of adiponectin was detected by qRT-PCR and western blotting, and pro- and anti-inflammatory factors were detected by ELISA. Adiponectin expression in AECOPD patients increased after treatment. TNF-α and apoptotic cells promoted adiponectin expression in HBECs in a dose-dependent manner, and apoptotic cells significantly promoted adiponectin secretion. IL-6 also promoted adiponectin expression, but it inhibited adiponectin expression at high doses and with long treatment times. LPS inhibited adiponectin expression, but when HBECs were pretreated with anti-TNF-α and then treated with LPS, the expression and secretion of adiponectin increased significantly with increasing anti-TNF-α concentrations. Adiponectin stimulated the secretion of pro-inflammatory factors in HBECs, but this effect was not concentration dependent. Adiponectin promoted the secretion of anti-inflammatory factors in a dose-dependent manner. Although LPS also stimulated HBECs to secrete pro-inflammatory and anti-inflammatory factors, adiponectin inhibited LPS-induced pro-inflammatory factor secretion and enhanced anti-inflammatory factor secretion. Many factors regulate the expression and secretion of adiponectin, and adiponectin regulates the balance of the inflammatory response and inhibits further expansion of inflammation. SIGNIFICANCE OF THE STUDY: Many studies have shown that adiponectin is closely related to chronic obstructive pulmonary disease (COPD), but the specific role of adiponectin in COPD is still not well understood. Adiponectin expression in AECOPD patients increased after treatment. TNF-α, IL-6 and apoptotic cells promoted adiponectin expression in HBECs. Adiponectin stimulated the secretion of pro-inflammatory factors in HBECs, but this effect was not concentration dependent. Adiponectin promoted the secretion of anti-inflammatory factors in a dose-dependent manner. Adiponectin inhibited LPS-induced pro-inflammatory factor secretion and enhanced anti-inflammatory factor secretion. Therefore, many factors regulate the expression and secretion of adiponectin, and adiponectin regulates the balance of the inflammatory response and inhibits further expansion of inflammation.


Assuntos
Adiponectina/metabolismo , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Mucosa Respiratória/metabolismo , Idoso , Linhagem Celular , Células Epiteliais/patologia , Feminino , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Mucosa Respiratória/patologia
16.
Front Oncol ; 11: 812033, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35155203

RESUMO

BACKGROUND: There was no consensus for management of asymptomatic endometrial polyps (EPs) up to date. OBJECTIVE: The aim of present study was to determine the risk factors of malignant lesions in EPs diagnosed by ultrasound and establish a noninvasive predictor to decrease unnecessary hysteroscopy for EPs. STUDY DESIGN: We reviewed the records of all consecutive patients who underwent hysteroscopy for EPs in the Women's Hospital School of Medicine Zhejiang University between January 1, 2001 and December 31, 2018. The patients with histological diagnoses of atypical hyperplasia or cancer were defined as malignancy, while the patients with histological diagnoses of benign lesions were randomly selected as benign group according to the ratio of 1:4 (malignancy:benign), matching by age and year of hospitalization. Logistic regression analysis was used to analyze the clinical parameters for predicting malignancy of EPs. A Chi-squared automatic interaction detection (CHAID) decision tree analysis was performed to find a noninvasive predictor. The sensitivity, specificity, and the receiver operating characteristic curve (ROC) were used for assess the efficacy of the noninvasive predictor. New diagnosed EPs patients received in 2019 were used for verifying the accuracy of the noninvasive predictor. RESULTS: The age in 15,790 cases of benign lesions was significantly younger than that in 230 malignancy cases (41.97 ± 11.53 year vs 53.31 ± 11.61 years, p <0.001). AUB (OR 7.306, 95%CI 4.927-10.835), large EPs (OR 2.595, 95%CI 1.662-4.052), and blood flow signal in EPs (OR 2.690, 95%CI 1.872-3.866) were independent predictive factors of malignancy in all enrolled patients. A noninvasive predictor for malignancy of EPs was established, through combining with AUB, large polyps and blood flow signal. This predictor presented excellent sensitivity and NPV (91.3 and 95.8%), with acceptable specificity and AUC (0.801). Further validation in new diagnosed EPs also suggested excellent sensitivity and reasonable specificity (100 and 58.5%) of the predictor. Factors such as thickened endometrial thickness, menopause shorter than 10 years, hypertension, obesity and nulliparous were also validated as independent predictors of malignancy in different subgroup analysis. CONCLUSIONS: The noninvasive predictor combined with other risk factors from subgroup analysis would be reliable to distinguish the benign lesions from malignancy for EPs diagnosed by ultrasound.

17.
Chin Med J (Engl) ; 133(16): 1915-1921, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32826454

RESUMO

BACKGROUND: Due to airway remodeling and emphysematous destruction in the lung, the two classical clinical phenotypes of chronic obstructive pulmonary disease (COPD) are emphysema and bronchiolitis. The present study was designed to investigate the levels of small airway immunoglobulin A (IgA) in COPD with "emphysema phenotype." The study also evaluated the associations between the small airway IgA levels and the severity of disease by the extent of emphysema versus airflow limitation. METHODS: Thirty patients (20 with COPD and ten healthy smokers) undergoing lung resection surgery for a solitary peripheral nodule were included. The study was conducted from January 2015 to December 2018 in the Shanxi Dayi Hospital. The presence of small airway IgA expression was determined in the lung by immunohistochemistry. In vivo, Wistar rats were exposed to silica by intratracheal instillation. Rats were sacrificed at 15 and 30 days after exposure of silica (n = 10 for each group). We also evaluated airway IgA from rats. RESULTS: Small airway secretory IgA (sIgA), dimeric IgA (dIgA), and dIgA/sIgA of Global Initiative for Chronic Obstructive Lung Disease grade 1-2 COPD patients showed no difference compared with smoking control subjects (5.15 ±â€Š1.53 vs. 6.03 ±â€Š0.85; 1.94 ±â€Š0.66 vs. 1.67 ±â€Š0.04; 41.69 ±â€Š21.02 vs. 28.44 ±â€Š9.45, all P > 0.05). dIgA/sIgA level in the lung of COPD patients with emphysema showed higher levels than that of COPD patients without emphysema (51.89 ±â€Š24.81 vs. 31.49 ±â€Š9.28, P = 0.03). The percentage of low-attenuation area below 950 Hounsfield units was positively correlated with dIgA/sIgA levels (r = 0.45, P = 0.047), but not associated with the severity of disease by spirometric measurements (forced expiratory volume in the first second %pred, P > 0.05). Likewise, in the rat study, significant differences in sIgA, dIgA, dIgA/sIgA, mean linear intercept, mean alveoli number, and mean airway thickness of bronchioles (VV airway, all P < 0.01) were only observed between control rats and those exposed for 30 days. However, in the group exposed for 15 days, although the VV airway was higher than that in normal rats (27.61 ±â€Š2.26 vs. 20.39 ±â€Š1.99, P < 0.01), there were no significant differences in IgA and emphysema parameters between the two groups (all P > 0.05). CONCLUSION: Airway IgA concentrations in mild and moderate COPD patients are directly associated with the severity of COPD with "emphysema phenotype" preceding severe airway limitation. This finding suggests that small airway IgA might play an important role in the pathophysiology of COPD, especially emphysema phenotype.


Assuntos
Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Animais , Volume Expiratório Forçado , Humanos , Imunoglobulina A , Ratos , Ratos Wistar
18.
Front Neurosci ; 14: 651, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655362

RESUMO

BACKGROUND: Selective loss of dopaminergic neurons and diminished putamen gray matter volume (GMV) represents a central feature of Parkinson's disease (PD). Recent studies have reported specific effects of kinectin 1 gene (KTN1) variants on the putamen GMV. OBJECTIVE: To examine the relationship of KTN1 variants, KTN1 mRNA expression in the putamen and substantia nigra pars compacta (SNc), putamen GMV, and PD. METHODS: We examined the associations between PD and a total of 1847 imputed KTN1 single nucleotide polymorphisms (SNPs) in one discovery sample [2,000 subjects with PD vs. 1,986 healthy controls (HC)], and confirmed the nominally significant associations (p < 0.05) in two replication samples (900 PD vs. 867 HC, and 940 PD vs. 801 HC, respectively). The regulatory effects of risk variants on the KTN1 mRNA expression in putamen and SNc and the putamen GMV were tested. We also quantified the expression levels of KTN1 mRNA in the putamen and/or SNc for comparison between PD and HC in five independent cohorts. RESULTS: Six replicable and two non-replicable KTN1-PD associations were identified (0.009 ≤ p ≤ 0.049). The major alleles of five SNPs, including rs12880292, rs8017172, rs17253792, rs945270, and rs4144657, significantly increased risk for PD (0.020 ≤ p ≤ 0.049) and putamen GMVs (19.08 ≤ ß ≤ 60.38; 2.82 ≤ Z ≤ 15.03; 5.0 × 10-51 ≤ p ≤ 0.018). The risk alleles of five SNPs, including rs8017172, rs17253792, rs945270, rs4144657, and rs1188184 also significantly increased the KTN1 mRNA expression in the putamen or SNc (0.021 ≤ p ≤ 0.046). The KTN1 mRNA was abundant in the putamen and/or SNc across five independent cohorts and differentially expressed in the SNc between PD and HC in one cohort (p = 0.047). CONCLUSION: There was a consistent, significant, replicable, and robust positive relationship among the KTN1 variants, PD risk, KTN1 mRNA expression in putamen, and putamen volumes, and a modest relation between PD risk and KTN1 mRNA expression in SNc, suggesting that KTN1 may play a functional role in the development of PD.

19.
Nanoscale ; 12(28): 15169-15174, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32662483

RESUMO

Visible-light-driven photocatalysts have shown tremendous prospects in solving the energy crisis and environmental problems, thanks to their wide spectral response and high quantum efficiency. Several strategies including the expansion of visible light response and the improvement of solar energy utilization and photocatalytic quantum efficiency via more effective separation of photogenerated carriers are the current focuses of research that direct the design and fabrication of viable photocatalysts. Herein, a series of composite photocatalysts assembled from plasmonic Cu nanoparticles (NPs) and Zn3In2S6 (ZIS) solid solutions were synthesized by means of a simple solvothermal method. In comparison with the pristine ZIS semiconductor, Cu NP loaded ZIS solid solutions showed greatly enhanced photocatalytic activity, selectivity and stability towards CO2 reduction under visible irradiation. Of note was that the optimized ZIS-Cu2 exhibited an enhanced CH4 production rate of ca. 292 µL g-1 h-1 and a selectivity of ca. 71.1%, which were among the highest numbers reported hitherto. The localized surface plasmon resonance (LSPR) effect, shown by surface Cu NPs, was believed to play a critical role in the enhanced CO2 photoreduction efficiency. More importantly, the introduction of plasmonic Cu NPs could restrain the recombination of photogenerated electron-hole pairs and promote the migration of photogenerated electrons to better participate in the photocatalytic CO2 reduction in the presence of water vapor. This work thus provides a facile means to design robust and flexible composite photocatalysts for visible-light-driven CO2 photoreduction with high efficiency.

20.
Lancet Respir Med ; 8(11): 1081-1093, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32598906

RESUMO

BACKGROUND: Small airway dysfunction is a common but neglected respiratory abnormality. Little is known about its prevalence, risk factors, and prognostic factors in China or anywhere else in the world. We aimed to estimate the prevalence of small airway dysfunction using spirometry before and after bronchodilation, both overall and in specific population subgroups; assess its association with a range of lifestyle and environmental factors (particularly smoking); and estimate the burden of small airway dysfunction in China. METHODS: From June, 2012, to May, 2015, the nationally representative China Pulmonary Health study invited 57 779 adults to participate using a multistage stratified sampling method from ten provinces (or equivalent), and 50 479 patients with valid lung function testing results were included in the analysis. We diagnosed small airway dysfunction on the basis of at least two of the following three indicators of lung function being less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow (FEF) 50%, and FEF 75%. Small airway dysfunction was further categorised into pre-small airway dysfunction (defined as having normal FEV1 and FEV1/forced vital capacity [FVC] ratio before bronchodilator inhalation), and post-small airway dysfunction (defined as having normal FEV1 and FEV1/FVC ratio both before and after bronchodilator inhalation). Logistic regression yielded adjusted odds ratios (ORs) for small airway dysfunction associated with smoking and other lifestyle and environmental factors. We further estimated the total number of cases of small airway dysfunction in China by applying present study findings to national census data. FINDINGS: Overall the prevalence of small airway dysfunction was 43·5% (95% CI 40·7-46·3), pre-small airway dysfunction was 25·5% (23·6-27·5), and post-small airway dysfunction was 11·3% (10·3-12·5). After multifactor regression analysis, the risk of small airway dysfunction was significantly associated with age, gender, urbanisation, education level, cigarette smoking, passive smoking, biomass use, exposure to high particulate matter with a diameter less than 2·5 µm (PM2·5) concentrations, history of chronic cough during childhood, history of childhood pneumonia or bronchitis, parental history of respiratory diseases, and increase of body-mass index (BMI) by 5 kg/m2. The ORs for small airway dysfunction and pre-small airway dysfunction were similar, whereas larger effect sizes were generally seen for post-small airway dysfunction than for either small airway dysfunction or pre-small airway dysfunction. For post-small airway dysfunction, cigarette smoking, exposure to PM2·5, and increase of BMI by 5 kg/m2 were significantly associated with increased risk, among preventable risk factors. There was also a dose-response association between cigarette smoking and post-small airway dysfunction among men, but not among women. We estimate that, in 2015, 426 (95% CI 411-468) million adults had small airway dysfunction, 253 (238-278) million had pre-small airway dysfunction, and 111 (104-126) million had post-small airway dysfunction in China. INTERPRETATION: In China, spirometry-defined small airway dysfunction is highly prevalent, with cigarette smoking being a major modifiable risk factor, along with PM2·5 exposure and increase of BMI by 5 kg/m2. Our findings emphasise the urgent need to develop and implement effective primary and secondary prevention strategies to reduce the burden of this condition in the general population. FUNDING: Ministry of Science and Technology of China; National Natural Science Foundation of China; National Health Commission of China.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Broncopatias/epidemiologia , Broncopatias/etiologia , Broncodilatadores/administração & dosagem , Obesidade/complicações , Fumar/efeitos adversos , Adulto , Distribuição por Idade , Broncopatias/diagnóstico , Broncopatias/tratamento farmacológico , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Testes de Função Respiratória , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Fumar/epidemiologia , Espirometria , Capacidade Vital/fisiologia , Adulto Jovem
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