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1.
BMC Cancer ; 24(1): 1241, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39379833

RESUMEN

BACKGROUND & AIMS: The benefit of postoperative adjuvant transcatheter arterial chemoembolization (pTACE) for patients with hepatocellular carcinoma (HCC), especially those with Child-Pugh (CP) B, remains controversial. This study aimed to assess the survival benefit of pTACE for HCC patients with CP B. METHODS: Data from 297 HCC patients with CP B7 or B8 were analyzed, dividing them into groups with and without pTACE (70, 23.6% vs. 227, 76.4%). Propensity score matching (PSM) was used to control for confounding bias, and competing-risk regression was applied to address bias from non-cancer-specific death (NCSD). RESULTS: Preliminary findings suggest that pTACE did not increase the incidence of severe complications in HCC patients with CP B7 or B8. Survival analysis indicated that the group receiving pTACE had better overall survival and recurrence-free survival than the group without pTACE after PSM. Furthermore, competitive risk analysis revealed that pTACE was an independent prognostic factor associated with reduced cancer-specific death incidence (subdistribution hazard ratio [SHR] 0.644, 95%CI: 0.378-0.784, P = 0.011) and recurrence (SHR 0.635, 95% CI: 0.379-0.855, P = 0.001). Importantly, pTACE did not increase NCSD. Subgroup analysis corroborated these results. CONCLUSION: Adjuvant TACE demonstrates the potential to significantly enhance the long-term prognosis of HCC patients with CP B7 or B8 following hepatectomy, particularly those with multiple tumors, large tumor size, macrovascular or microvascular invasion, and narrow resection margin. Hence, pTACE should be considered for patients at high risk of recurrence following thorough evaluation.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Hepatectomía , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Masculino , Quimioembolización Terapéutica/métodos , Femenino , Persona de Mediana Edad , Anciano , Puntaje de Propensión , Recurrencia Local de Neoplasia/epidemiología , Pronóstico , Estudios Retrospectivos , Adulto , Resultado del Tratamiento , Quimioterapia Adyuvante/métodos
2.
BMC Cancer ; 24(1): 727, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877445

RESUMEN

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Hepatectomía , Humanos , Colangiocarcinoma/cirugía , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Anciano , Curva ROC , Estudios Retrospectivos , Estimación de Kaplan-Meier , Adulto , Factores de Riesgo
3.
Nutr Metab Cardiovasc Dis ; 34(11): 2570-2578, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39098378

RESUMEN

BACKGROUND AND AIM: Cardiometabolic diseases (CMDs) are leading causes of death and disability, but little is known about the additive mortality effects of multiple CMDs. This study aimed to examine the association between single and multiple CMDs and all-cause mortality among older Chinese population. METHODS AND RESULTS: Using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database, we analyzed data from 2008 to 2018 to assess the relationship between CMDs and mortality. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for single and multiple CMDs. At baseline, 11,351 participants (56.9% female) aged 60 years or older were included. 11.91% of participants had a single CMD, 1.51% had two CMDs, and 0.22% had three CMDs. Over a decade follow-up, 8992 deaths (79.2%) were recorded. A dose-response relationship was observed, with the mortality risk increasing by 17% for each additional disease. The fully-adjusted HRs for all-cause mortality were 1.16, 1.36, and 2.03 for one, two, and three CMDs, respectively. Larger effects of single and multiple CMDs were observed in the male group (P = 0.015) and the younger senior group (P < 0.001). CONCLUSIONS: This large-scale study found that CMDs multiply mortality risks, especially in younger seniors and males. The risk is highest when heart disease and stroke coexist, and diabetes further increases it. Public health efforts should prioritize evidence-based management and prevention of CMDs.


Asunto(s)
Factores de Riesgo Cardiometabólico , Causas de Muerte , Bases de Datos Factuales , Humanos , Masculino , Femenino , Anciano , China/epidemiología , Estudios Prospectivos , Persona de Mediana Edad , Medición de Riesgo , Factores de Edad , Anciano de 80 o más Años , Factores de Tiempo , Enfermedades Cardiovasculares/mortalidad , Multimorbilidad , Pronóstico , Factores Sexuales , Factores de Riesgo , Pueblos del Este de Asia
4.
Molecules ; 29(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38276629

RESUMEN

Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising therapeutic target for treating various cancers (such as breast cancer, liver cancer, etc.) and other diseases (blood diseases, cardiovascular diseases, etc.), owing to its observed overexpression, thereby presenting significant opportunities in drug development. Since its discovery in 2004, extensive research has been conducted on LSD1 inhibitors, with notable contributions from computational approaches. This review systematically summarizes LSD1 inhibitors investigated through computer-aided drug design (CADD) technologies since 2010, showcasing a diverse range of chemical scaffolds, including phenelzine derivatives, tranylcypromine (abbreviated as TCP or 2-PCPA) derivatives, nitrogen-containing heterocyclic (pyridine, pyrimidine, azole, thieno[3,2-b]pyrrole, indole, quinoline and benzoxazole) derivatives, natural products (including sanguinarine, phenolic compounds and resveratrol derivatives, flavonoids and other natural products) and others (including thiourea compounds, Fenoldopam and Raloxifene, (4-cyanophenyl)glycine derivatives, propargylamine and benzohydrazide derivatives and inhibitors discovered through AI techniques). Computational techniques, such as virtual screening, molecular docking and 3D-QSAR models, have played a pivotal role in elucidating the interactions between these inhibitors and LSD1. Moreover, the integration of cutting-edge technologies such as artificial intelligence holds promise in facilitating the discovery of novel LSD1 inhibitors. The comprehensive insights presented in this review aim to provide valuable information for advancing further research on LSD1 inhibitors.


Asunto(s)
Productos Biológicos , Inhibidores Enzimáticos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Lisina , Simulación del Acoplamiento Molecular , Inteligencia Artificial , Diseño de Fármacos , Histona Demetilasas/metabolismo , Relación Estructura-Actividad
5.
Molecules ; 29(11)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38893524

RESUMEN

The stimulator of interferon genes (STING) plays a significant role in immune defense and protection against tumor proliferation. Many cyclic dinucleotide (CDN) analogues have been reported to regulate its activity, but the dynamic process involved when the ligands activate STING remains unclear. In this work, all-atom molecular dynamics simulations were performed to explore the binding mode between human STING (hSTING) and four cyclic adenosine-inosine monophosphate analogs (cAIMPs), as well as 2',3'-cGMP-AMP (2',3'-cGAMP). The results indicate that these cAIMPs adopt a U-shaped configuration within the binding pocket, forming extensive non-covalent interaction networks with hSTING. These interactions play a significant role in augmenting the binding, particularly in interactions with Tyr167, Arg238, Thr263, and Thr267. Additionally, the presence of hydrophobic interactions between the ligand and the receptor further contributes to the overall stability of the binding. In this work, the conformational changes in hSTING upon binding these cAIMPs were also studied and a significant tendency for hSTING to shift from open to closed state was observed after binding some of the cAIMP ligands.


Asunto(s)
Proteínas de la Membrana , Simulación de Dinámica Molecular , Unión Proteica , Humanos , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Sitios de Unión , Nucleótidos Cíclicos/química , Nucleótidos Cíclicos/metabolismo , Ligandos , Interacciones Hidrofóbicas e Hidrofílicas
6.
HPB (Oxford) ; 26(8): 1062-1071, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38830783

RESUMEN

BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.


Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Laparoscopía , Neoplasias Hepáticas , Complicaciones Posoperatorias , Puntaje de Propensión , Procedimientos Quirúrgicos Robotizados , Humanos , Carcinoma Hepatocelular/cirugía , Hepatectomía/efectos adversos , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Masculino , Laparoscopía/efectos adversos , Femenino , Procedimientos Quirúrgicos Robotizados/efectos adversos , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Anciano , Bases de Datos Factuales , Tiempo de Internación , Factores de Riesgo , Factores de Tiempo , Medición de Riesgo , Adulto
7.
Environ Sci Technol ; 57(23): 8496-8505, 2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37267095

RESUMEN

To investigate the relation of smoking and microplastic inhalation, we conducted a prospective study combining population-based and experimental work. Bronchoalveolar lavage fluid (BALF) samples from 17 smokers and 15 nonsmokers were collected in Zhuhai City, China. We simulated an active smoking model to explore the contribution of smoking to inhaled microplastics. The characteristics of microplastics in BALF samples and cigarette smoke were determined using laser direct infrared spectroscopy. We compared the differences between smokers and nonsmokers as well as between cigarette smoke and control groups. Microplastics were identified positive in all BALF samples. Smokers had higher concentrations of total microplastics (25.86 particles/g), polyurethane (11.34 particles/g), and silicone (1.15 particles/g) than nonsmokers. In the cigarette smoking simulation model, higher concentrations of total microplastics (9.99 particles/L), polyurethane (4.66 particles/L), and silicone (2.78 particles/L) were present in the cigarette smoke than those in the control group. We confirmed and extended the evidence on the presence of microplastics in the lower respiratory tract. These findings also provide new evidence on the relation between cigarette smoking and microplastic inhalation.


Asunto(s)
Microplásticos , Plásticos , Poliuretanos , Estudios Prospectivos , Sistema Respiratorio , Fumar
8.
Environ Sci Technol ; 57(6): 2435-2444, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36718593

RESUMEN

Microplastics (MPs) are abundant in air, but evidence of their deposition in the respiratory tract is limited. We conducted a prospective case series to investigate the deposition of microplastics in bronchoalveolar lavage fluid (BALF) and determine the internal dose of MPs via inhalation. Eighteen never-smokers aged 32-74 years who underwent fiberoptic bronchoscopy with BALF were recruited from Zhuhai, China. Control samples were obtained by performing the same procedure using isotonic saline instead of BALF. Laser direct infrared spectroscopy combined with scanning electron microscopy detected the presence and characteristics of MPs and quantitatively analyzed the microplastic in BALF and control samples. Concentrations of total and specific MPs in BALF and control samples were compared using the Wilcox test. Thirteen types of MPs were observed in 18 BALF samples. Polyethylene (PE, 86.1%) was the most abundant in BALF, followed by poly(ethylene terephthalate) (PET, 7.5%) and polypropylene (PP, 1.9%). Compared with the control samples, BALF had significantly higher concentrations of PE (median [IQR] of BALF: 0.38 [8.05] N/g), PET (0.26 [0.54] N/g), polyurethane (0.16 [0.24] N/g), PP (0.16 [0.11] N/g), and total MPs (0.91 [6.58] N/g). The presence of MPs in BALF provides novel evidence that MPs penetrate deep into the respiratory tract.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Humanos , Líquido del Lavado Bronquioalveolar/química , Plásticos , Fumadores , Polipropilenos , Monitoreo del Ambiente
9.
BMC Urol ; 23(1): 206, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38082379

RESUMEN

BACKGROUND: In this study, we explored the diagnostic performances of multiparametric magnetic resonance imaging (mpMRI), 68 Ga-PSMA-11 PET/CT and combination of 68 Ga-PSMA-11 PET/CT and mpMRI (mpMRI + PET/CT) for extracapsular extension (ECE). Based on the analyses above, we tested the feasibility of using mpMRI + PET/CT results to predict T staging in prostate cancer patients. METHODS: By enrolling 75 patients of prostate cancer with mpMRI and 68 Ga-PSMA-11 PET/CT before radical prostatectomy, we analyzed the detection performances of ECE in mpMRI, 68 Ga-PSMA-11 PET/CT and mpMRI + PET/CT on their lesion images matched with their pathological sample images layer by layer through receiver operating characteristics (ROC) analysis. By inputting the lesion data into Prostate Imaging Reporting and Data System (PI-RADS), we divided the lesions into different PI-RADS scores. The improvement of detecting ECE was analyzed by net reclassification improvement (NRI). The predictors for T staging were evaluated by using univariate and multivariable analysis. The Kappa test was used to evaluate the prediction ability. RESULTS: One hundred three regions of lesion were identified from 75 patients. 50 of 103 regions were positive for ECE. The ECE diagnosis AUC of mpMRI + PET/CT is higher than that of mpMRI alone (ΔAUC = 0.101; 95% CI, 0.0148 to 0.1860; p < 0.05, respectively). Compared to mpMRI, mpMRI + PET/CT has a significant improvement in detecting ECE in PI-RADS 4-5 (NRI 36.1%, p < 0.01). The diagnosis power of mpMRI + PET/CT was an independent predictor for T staging (p < 0.001) in logistic regression analysis. In patients with PI-RADS 4-5 lesions, 40 of 46 (87.0%) patients have correct T staging prediction from mpMRI + PET/CT (κ 0.70, p < 0.01). CONCLUSION: The prediction of T staging in PI-RADS 4-5 prostate cancer patients by mpMRI + PET/CT had a quite good performance.


Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radioisótopos de Galio , Neoplasias de la Próstata/patología , Imagen por Resonancia Magnética/métodos
10.
Surg Today ; 53(3): 322-331, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35986784

RESUMEN

PURPOSE: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains controversial, especially for tumors larger than 5 cm. We compared the short- and long-term outcomes of laparoscopic and open liver resection (OLR) for large HCC. METHODS: Patients with large HCC after curative hepatectomy were enrolled. To compare the short-term outcomes, propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed to reduce the effect of confounding factors, respectively. Subsequently, Cox-regression analyses were conducted to identify the independent risk factors associated with decreased recurrence-free survival (RFS) and poor overall survival (OS). RESULT: There were 265 patients enrolled in the final analysis: 146 who underwent OLR and 119 who underwent LLR. There was no significant difference between the OLR and LLR groups according to PSM and IPTW analysis (all P > 0.05). Multivariable analysis revealed that LLR was not independently associated with poorer OS (HR 1.15, 95% CI 0.80-1.67, P = 0.448) or RFS (HR 1.22, 95% CI 0.88-1.70, P = 0.238). CONCLUSION: There were no significant differences in perioperative complications or long-term prognosis between LLR and OLR for large HCC, which provides evidence for standard laparoscopic surgical practice with adequate surgeon experience and careful patient selection.


Asunto(s)
Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Puntaje de Propensión , Estudios Retrospectivos , Laparoscopía/efectos adversos , Tiempo de Internación
11.
BMC Surg ; 23(1): 239, 2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37592274

RESUMEN

BACKGROUND AND AIMS: Preoperative prediction of microvascular invasion (MVI) using a noninvasive method remain unresolved, especially in HBV-related in intrahepatic cholangiocarcinoma (ICC). This study aimed to build and validate a preoperative prediction model for MVI in HBV-related ICC. METHODS: Patients with HBV-associated ICC undergoing curative surgical resection were identified. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors of MVI in the training cohort. Then, a prediction model was built by enrolling the independent risk factors. The predictive performance was validated by receiver operator characteristic curve (ROC) and calibration in the validation cohort. RESULTS: Consecutive 626 patients were identified and randomly divided into the training (418, 67%) and validation (208, 33%) cohorts. Multivariate analysis showed that TBIL, CA19-9, tumor size, tumor number, and preoperative image lymph node metastasis were independently associated with MVI. Then, a model was built by enrolling former fiver risk factors. In the validation cohort, the performance of this model showed good calibration. The area under the curve was 0.874 (95% CI: 0.765-0.894) and 0.729 (95%CI: 0.706-0.751) in the training and validation cohort, respectively. Decision curve analysis showed an obvious net benefit from the model. CONCLUSION: Based on clinical data, an easy model was built for the preoperative prediction of MVI, which can assist clinicians in surgical decision-making and adjuvant therapy.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Virus de la Hepatitis B , Colangiocarcinoma/cirugía , Antígeno CA-19-9 , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos
12.
Respir Res ; 23(1): 71, 2022 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-35346202

RESUMEN

BACKGROUND: Pneumonia is a major contributor to hospital admission for patients with chronic obstructive pulmonary disease (COPD). However, evidence for acute effects of ambient air pollution exposure on pneumonia hospital admission among patients with COPD is scarce. We aimed to examine the association between short-term exposure to ambient air pollution and pneumonia hospital admission among patients with COPD. METHODS: We enrolled COPD cases aged ≥ 60 years old and further filtered those who were admitted into hospitals from pneumonia during 2016-2019 in Guangdong province, China for main analysis. A time-stratified case-crossover design was applied to investigate the association and conditional logistic regression model was used for data analysis. We performed inverse distance weighting method to estimate daily individual-level exposure on particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5), particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) based on personal residential addresses. RESULTS: We included 6473 pneumonia hospital admissions during the study period. Each interquartile range (IQR) increase in PM2.5 (lag 2; IQR, 22.1 µg/m3), SO2 (lag 03; IQR, 4.2 µg/m3), NO2 (lag 03; IQR, 21.4 µg/m3), and O3 (lag 04; IQR, 57.9 µg/m3) was associated with an odds ratio in pneumonia hospital admission of 1.043 (95% CI: 1.004-1.083), 1.081 (95% CI: 1.026-1.140), 1.045 (95% CI: 1.005-1.088), and 1.080 (95% CI: 1.018-1.147), respectively. Non-linear trends for PM2.5, PM10, and SO2 were observed in the study. Sex, age at hospital admission, and season at hospital admission did not modify the associations. CONCLUSIONS: We found significantly positive associations of short-term exposure to PM2.5, SO2, NO2, and O3 with pneumonia hospital admission among COPD patients. It provides new insight for comprehensive pneumonia prevention and treatment among COPD patients.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Neumonía , Enfermedad Pulmonar Obstructiva Crónica , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Estudios Cruzados , Hospitales , Humanos , Persona de Mediana Edad , Neumonía/inducido químicamente , Neumonía/diagnóstico , Neumonía/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología
13.
BMC Cancer ; 22(1): 677, 2022 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-35725444

RESUMEN

Immunotherapy has emerged as a robust clinical strategy for cancer treatment. PD1/PD-L1 inhibitors have been used as second-line therapy for urothelial carcinoma due to the high tumor mutational burden. Despite the efficacy of the treatment is significant, the response rate is still poor. The tumor immune microenvironment plays a key role in the regulation of immunotherapeutic efficacy. However, a comprehensive understanding of the intricate microenvironment in clinical samples remains unclear. To obtain detailed systematic tumor immune profile, we performed an in-depth immunoassay on 12 human urothelial carcinoma tissue samples and 14 paratumor tissue samples using mass cytometry. Among the large number of cells assayed, we identified 71 T-cell phenotypes, 30 tumor-associated macrophage phenotypes. T cell marker expression profiles showed that almost all T cells in the tumor tissue were in a state of exhaustion. CD38 expression on tumor-associated macrophages (TAMs) was significantly higher than PDL1, and CD38+ TAMs were closely associated with immunosuppression. CD38 may be a more suitable target for immunotherapy in urothelial carcinoma compared to PD1/PDL1. This single-cell analysis of clinical samples expands our insights into the immune microenvironment of urothelial carcinoma and reveals potential biomarkers and targets for immunotherapy development.


Asunto(s)
Carcinoma de Células Transicionales , Inmunoterapia , Neoplasias de la Vejiga Urinaria , Antígeno B7-H1/metabolismo , Carcinoma de Células Transicionales/inmunología , Humanos , Linfocitos T , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/inmunología
14.
Eur J Neurol ; 29(7): 1994-2005, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35363940

RESUMEN

BACKGROUND: Short-term exposure to ambient air pollution has been linked to increased risk of stroke mortality, but its adverse effects on mortality from specific types of stroke including ischemic stroke and hemorrhagic stroke remain poorly understood. METHODS: Using the China National Mortality Surveillance System, we conducted a time-stratified case-crossover study among 412,567 stroke deaths in Jiangsu province, China during 2015-2019. Residential daily PM2.5 , PM10 , SO2 , NO2 , CO, and O3 exposure concentrations were extracted from the ChinaHighAirPollutants dataset for each subject. Conditional logistic regression models were performed to conduct exposure-response analyses. RESULTS: Each 10 µg/m3 increase of PM2.5 , PM10 , SO2 , NO2 , CO, and O3 was respectively associated with a 1.44%, 0.93%, 5.55%, 2.90%, 0.148%, and 0.54% increase in odds of mortality from ischemic stroke, which was significantly stronger than that from hemorrhagic stroke (percent change in odds: 0.74%, 0.51%, 3.11%, 1.15%, 0.090%, and 0.10%). The excess fraction of ischemic stroke mortality associated with PM2.5 , PM10 , SO2 , NO2 , CO, and O3 exposure was 6.90%, 6.48%, 8.21%, 8.61%, 9.67%, and 4.76%, respectively, which was also significantly higher than that of hemorrhagic stroke mortality (excess fraction: 3.49%, 3.48%, 4.69%, 3.48%, 5.86%, and 0.88%). These differences in adverse effects generally remained across sex, age, and season. CONCLUSIONS: Short-term exposure to ambient air pollution was significantly associated with increased risk of both ischemic and hemorrhagic stroke mortality and posed considerable excess mortality. Our results suggest that air pollution exposure may lead to substantially greater adverse effects on mortality from ischemic stroke than that from hemorrhagic stroke.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , China/epidemiología , Estudios Cruzados , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Humanos , Isquemia , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/análisis , Material Particulado/efectos adversos , Material Particulado/análisis , Accidente Cerebrovascular/epidemiología
15.
Environ Res ; 214(Pt 4): 114116, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35988831

RESUMEN

BACKGROUND: Whether ambient temperature exposure contributes to death from asthma remains unknown to date. We therefore conducted a case-crossover study in China to quantitatively evaluate the association and burden of ambient temperature exposure on asthma mortality. METHODS: Using data from the National Mortality Surveillance System in China, we conducted a time-stratified case-crossover study of 15 888 individuals who lived in Hubei and Jiangsu province, China and died from asthma as the underlying cause in 2015-2019. Individual-level exposures to air temperature and apparent temperature on the date of death and 21 days prior were assessed based on each subject's residential address. Distributed lag nonlinear models based on conditional logistic regression were used to quantify exposure-response associations and calculate fraction and number of deaths attributable to non-optimum ambient temperatures. RESULTS: We observed a reverse J-shaped association between air temperature and risk of asthma mortality, with a minimum mortality temperature of 21.3 °C. Non-optimum ambient temperature is responsible for substantial excess mortality from asthma. In total, 26.3% of asthma mortality were attributable to non-optimum temperatures, with moderate cold, moderate hot, extreme cold and extreme hot responsible for 21.7%, 2.4%, 2.1% and 0.9% of asthma mortality, respectively. The total attributable fraction and number was significantly higher among adults aged less than 80 years in hot temperature. CONCLUSIONS: Exposure to non-optimum ambient temperature, especially moderate cold temperature, was responsible for substantial excess mortality from asthma. These findings have important implications for planning of public-health interventions to minimize the adverse respiratory damage from non-optimum ambient temperature.


Asunto(s)
Asma , Frío , Adulto , Asma/epidemiología , China/epidemiología , Estudios Cruzados , Calor , Humanos , Mortalidad , Temperatura
16.
Ecotoxicol Environ Saf ; 236: 113498, 2022 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-35421825

RESUMEN

BACKGROUND: Exposure to non-optimum ambient temperature has been linked to increased risk of total cardiovascular disease (CVD) mortality; however, the adverse effects on mortality from specific types of CVD remain less understood. OBJECTIVES: To comprehensively investigate the association of ambient temperature with cause-specific CVD mortality, and to estimate and compare the corresponding mortality burden. METHODS: We conducted a time-stratified case-crossover study of 1000,014 CVD deaths in Jiangsu province, China during 2015-2019 using data from the China National Mortality Surveillance System. Residential daily 24-hour average temperature for each subject was extracted from a validated grid data at a spatial resolution of 0.0625° × 0.0625°. We fitted distributed lag non-linear models (DLNM) based on conditional logistic regression to quantitatively investigate the association of ambient temperature with total and cause-specific CVD mortality, which was used to further estimate mortality burden attributable to non-optimum ambient temperatures. RESULTS: With adjustment for relative humidity, we observed reverse J-shaped exposure-response associations of ambient temperature with total and cause-specific CVD mortality, with minimum mortality temperatures ranging from 19.5 °C to 23.0 °C. An estimated 20.3% of the total CVD deaths were attributable to non-optimum temperatures, while the attributable fraction (AF) of mortality from chronic rheumatic heart diseases, hypertensive diseases, ischemic heart diseases (IHD), pulmonary heart disease, stroke, and sequelae of stroke was 22.4%, 23.2%, 23.3%, 20.9%, 17.6% and 21.3%, respectively. For total and cause-specific CVDs, most deaths were attributable to moderate cold temperature. We observed significantly higher mortality burden from total and certain cause-specific CVDs in adults 80 years or older and those who were widowed. CONCLUSION: Exposure to ambient temperature was significantly associated with increased risk of cause-specific CVD mortality. The burden of CVD mortality attributable to non-optimum temperature was substantial especially in older and widowed adults, and significantly varied across specific types of CVD.


Asunto(s)
Enfermedades Cardiovasculares , Accidente Cerebrovascular , Adulto , Anciano , China/epidemiología , Frío , Estudios Cruzados , Calor , Humanos , Temperatura
17.
BMC Public Health ; 21(1): 1063, 2021 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-34088290

RESUMEN

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a global pandemic and an anxiety-provoking event. There are few studies to identify potential risk and protective factors related to anxiety during COVID-19 pandemic. METHODS: We collected information on demographic data and lifestyles by a web-based survey of 19,802 participants from 34 provinces in China during COVID-19 pandemic. Level of anxiety was evaluated using the Self-Rating Anxiety Scale. We used ordinal multivariable logistic regression to estimate the associations of anxiety level with potential risk and protective factors. We further developed a new score to simplify the assessment of anxiety during COVID-19 crisis. RESULTS: Among 19,802 participants, we found that those who were front-line medical personnel, suffered from chronic disease, with present symptoms of SARS-CoV-2 infection or contact history had 112, 93, 40 and 15% increased risk of higher anxiety level; while those with knowledge about personal protective measures or wore masks had 75 and 29% lower risk of higher anxiety level respectively. We developed a risk score by calculating the sum of single score of 17 factors. Each one increase of the risk score was associated with a 297% increase in anxiety index score. In categorical analysis, low risk (the risk score between 1 to 2), the moderate risk group (the risk score of 3) and high risk group (the risk score ≥ 4) had - 0.40 (95% CI: - 1.55, 0.76), 1.44 (95% CI: 0.27, 2.61) and 9.18 (95% CI: 8.04, 10.33) increase in anxiety index score, and 26% (95% CI: - 7, 72%), 172% (95% CI: 100, 270%), and 733% (95% CI: 516, 1026%) higher risk of anxiety respectively, when compared with the very low risk group (the risk score of 0). The AUC was 0.73 (95% CI, 0.72, 0.74) for the model fitted the developed risk score, with the cut-off point of 3.5. CONCLUSIONS: These findings revealed protective and risk factors associated with anxiety, and developed a simple method of identifying people who are at an increased risk of anxiety during COVID-19 pandemic.


Asunto(s)
COVID-19 , Pandemias , Ansiedad/epidemiología , China/epidemiología , Estudios Transversales , Depresión , Humanos , Pandemias/prevención & control , Factores Protectores , Factores de Riesgo , SARS-CoV-2 , Encuestas y Cuestionarios
18.
Ecotoxicol Environ Saf ; 228: 113034, 2021 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-34861442

RESUMEN

BACKGROUND: Chronic obstructive pulmonary disease (COPD) hospitalization has been linked with ambient air pollution. However, the evidence on respiratory health benefits from air pollution control policy in China is limited. OBJECTIVE: To investigate benefits from the Three-Year Action Plan to Win the Battle for a Blue Sky (TYAP) for tackling COPD hospitalization due to ambient air pollution. METHODS: We conducted a time-stratified case-crossover study of 138,015 COPD hospitalizations aged ≥ 60 years in Guangdong province, China during 2016-2019 to investigate respiratory health benefits from TYAP. Inverse distance weighting method was used to assess daily individual-level exposures to ambient air pollutants including particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5), particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3). Conditional logistic regression model was applied to analyze the associations between ambient air pollutants and COPD hospitalization. RESULTS: TYAP can modify the associations. Each 10 µg/m3 increase of exposure to PM2.5, PM10, and NO2 and 1 mg/m3 increase of exposure to CO were significantly associated with 2.5%, 2.0%, 3.0%, and 14.4% increase in odds of COPD hospitalization before TYAP, respectively; while 1.0%, 0.9%, 1.5%, and 5.8% increase in odds during TYAP. We found prominent declines in health burden of COPD hospitalizations due to air pollution among the elderly after TYAP implication when compared with that before TYAP. CONCLUSION: Reduced levels of ambient air pollutants by TYAP can effectively lower the risk for COPD hospitalization among the elderly, which provides evidence on the respiratory health benefits from consistent and effective air pollution control policy.

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