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1.
Theranostics ; 12(1): 340-361, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34987649

RESUMO

Background: Chitinase 3-like-1 (CHI3L1) is a secretion glycoprotein associated with the immunosuppressive tumor microenvironment (TME). The secretory mode of CHI3L1 makes it a promising target for cancer treatment. We have previously reported that Rab37 small GTPase mediates secretion of IL-6 in macrophages to promote cancer progression, whereas the roles of Rab37 in the intracellular trafficking and exocytosis of CHI3L1 are unclear. Methods: We examined the concentration of CHI3L1 in the culture medium of splenocytes and bone marrow derived macrophages (BMDMs) from wild-type or Rab37 knockout mice, and macrophage or T cell lines expressing wild type, active GTP-bound or inactive GDP-bound Rab37. Vesicle isolation, total internal reflection fluorescence microscopy, and real-time confocal microscopy were conducted. We developed polyclonal neutralizing-CHI3L1 antibodies (nCHI3L1 Abs) to validate the therapeutic efficacy in orthotopic lung, pancreas and colon cancer allograft models. Multiplex fluorescence immunohistochemistry was performed to detect the protein level of Rab37 and CHI3L1, and localization of the tumor-infiltrating immune cells in allografts from mice or tumor specimens from cancer patients. Results: We demonstrate a novel secretion mode of CHI3L1 mediated by the small GTPase Rab37 in T cells and macrophages. Rab37 mediated CHI3L1 intracellular vesicle trafficking and exocytosis in a GTP-dependent manner, which is abolished in the splenocytes and BMDMs from Rab37 knockout mice and attenuated in macrophage or T cell lines expressing the inactive Rab37. The secreted CHI3L1 activated AKT, ß-catenin and NF-κB signal pathways in cancer cells and macrophages to foster a protumor TME characterized by activating M2 macrophages and increasing the population of regulatory T cells. Our developed nCHI3L1 Abs showed the dual properties of reducing tumor growth/metastases and eliciting an immunostimulatory TME in syngeneic orthotopic lung, pancreas and colon tumor models. Clinically, high plasma level or intratumoral expression of CHI3L1 correlated with poor survival in 161 lung cancer, 155 pancreatic cancer and 180 colon cancer patients. Conclusions: These results provide the first evidence that Rab37 mediates CHI3L1 secretion in immune cells and highlight nCHI3L1 Abs that can simultaneously target both cancer cells and tumor microenvironment.

2.
Eur Phys J E Soft Matter ; 45(1): 4, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35038043

RESUMO

Vertex models describe biological tissues as tilings of polygons. In standard vertex models, the tissue dynamics result from a balance between isotropic stresses, which are associated with the bulk of the cells, and tensions associated with cell-cell interfaces. However, in this framework it is less obvious how to describe anisotropic stresses arising from the bulk of cells. In epithelia, such bulk anisotropic stresses could arise for instance through medial myosin fluctuations. Two recent publications-Tlili et al. (Proc Natl Acad Sci USA 116(51):25430-25439, 2019) and Comelles et al. (eLife 10:e57730, 2021)-have proposed different schemes to implement bulk anisotropic stresses in vertex models. Here we show that while both schemes transform in the same way under affine deformations, they lead to significantly different tissue dynamics. Our results are consistent with the interpretation that the Tilli et al. scheme describes bulk stresses that are uniform within each cell, while the Comelles et al. scheme corresponds to non-uniform bulk stresses. Finally, we wondered whether a standard vertex model can be fully expressed in terms of bulk cellular stresses alone. We find that, in general, neither scheme can mimic the vertex forces created by cell-cell interface tensions.


Assuntos
Modelos Biológicos , Anisotropia , Epitélio
3.
Sci Total Environ ; : 152150, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34864029

RESUMO

BACKGROUND/OBJECTIVE: Research suggests gestational exposure to particulate matter ≤2.5 µm (PM2.5) and extreme heat may independently increase risk of birth defects. We investigated whether duration of gestational extreme heat exposure modifies associations between PM2.5 exposure and specific congenital heart defects (CHDs). We also explored nonlinear exposure-outcome relationships. METHODS: We identified CHD case children (n = 2824) and non-malformed live-birth control children (n = 4033) from pregnancies ending between 1999 and 2007 in the National Birth Defects Prevention Study, a U.S. population-based multicenter case-control study. We assigned mothers 6-week averages of PM2.5 exposure during the cardiac critical period (postconceptional weeks 3-8) using the closest monitor within 50 km of maternal residence. We assigned a count of extreme heat days (EHDs, days above the 90th percentile of daily maximum temperature for year, season, and weather station) during this period using the closest weather station. Using generalized additive models, we explored logit-nonlinear exposure-outcome relationships, concluding logistic models were reasonable. We estimated joint effects of PM2.5 and EHDs on six CHDs using logistic regression models adjusted for mean dewpoint and maternal age, education, and race/ethnicity. We assessed multiplicative and additive effect modification. RESULTS: Conditional on the highest observed EHD count (15) and at least one critical period day during spring/summer, each 5 µg/m3 increase in average PM2.5 exposure was significantly associated with perimembranous ventricular septal defects (VSDpm; OR: 1.54 [95% CI: 1.01, 2.41]). High EHD counts (8+) in the same population were positively, but non-significantly, associated with both overall septal defects and VSDpm. Null or inverse associations were observed for lower EHD counts. Multiplicative and additive effect modification estimates were consistently positive in all septal models. CONCLUSIONS: Results provide limited evidence that duration of extreme heat exposure modifies the PM2.5-septal defects relationship. Future research with enhanced exposure assessment and modeling techniques could clarify these relationships.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(6): 1869-1874, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34893125

RESUMO

OBJECTIVE: To investigate the overview of thrombosis in myeloproliferative neoplasms(MPN) patients, and to explore the risk factors of thrombosis at diagnosis and during follow-up. METHODS: The clinical data of 388 MPN patients treated in our hospital were collected. The patients were followed up by outpatient and phone. The risk factors of thrombosis were analyzed by statistical methods. RESULTS: Among 388 MPN patients, 161 patients (41.49%) showed thromboses at diagnosis or during follow-up. Among them, 92.55% were arterial thromboses, 146 cases (96.27%) were complicated with thromboses at diagnosis, and 36 cases (11.46%) showed newly thromboses or progression of previous thromboses among the 314 received full follow-up patients. Age (P<0.001, HR:1.033, 95%CI:1.016-1.051), JAK2V617F mutation (P=0.037, HR:1.72, 95%CI: 1.033-2.862), hypertension (P<0.001, HR:2.639, 95%CI:1.659-4.197) and hyperlipidemia (P<0.001, HR:2.659, 95%CI:1.626-4.347) were the independent risk factors affecting thrombosis at diagnosis of the patients. During the follow-up, age (P=0.016, HR:1.032, 95%CI: 1.006-1.059) and previous thrombosis history (P=0.019, HR:2.194, 95%CI: 1.135-4.242) were the independent risk factors affecting the progression of thrombosis at different sites or on the basis of the previous thrombosis in the patients. CONCLUSION: Patients with advanced age, JAK2V617F mutation or complicated with hypertension and hyperlipidemia shows a higher risk of thrombosis at diagnosis, while the patients with advanced age or previous thrombosis history shows a higher risk of progression of thrombosis during the follow-up.

5.
J Biomed Nanotechnol ; 17(11): 2165-2175, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34906277

RESUMO

Despite the continuous improvement of leukemia treatment in the clinic, the overall 5-year disease-free survival of acute myeloid leukemia (AML) is only approximately 30%-60% due to relapse and the refractoriness of AML after traditional chemotherapy. Inhibition of poly(ADP-ribose) polymerase (PARP), a member of the DNA damage repair complex, has a strong antitumor effect in solid tumors. However, the role of PARP in AML remains unclear. We found that high levels of PARP1 and PARP2 were positively related to chemotherapy resistance and poor prognosis in patients with AML. Doxorubicin (DOX)-resistant AML cells highly expressed PAPR1 and PARP2. Knockdown of PARP1 and PARP2, or pharmaceutical inhibition of PARP by the PARP inhibitor (PARPi) BGB-290, significantly enhanced the cytotoxicity of DOX in AML cells due to increased DNA damage. PLGA-loading BGB-290 was properly self-assembled into stable BGB-290@PLGA nanoparticles (NPs), which is uniform particle size and good stability. BGB-290@PLGA is easily uptake by AML cell lines and stays for a long time. Combined with DOX, BGB-290@PLGA can significantly improve the chemosensitivity of AML cell lines. Furthermore, BGB-290 and DOX combination treatment dramatically repressed the onset of leukemia and prolonged the survival of THP-1 xenografted mice. Overall, this study demonstrated that PARPi with traditional chemotherapy could be an efficient therapeutic strategy for AML.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Fluorenos/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Camundongos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
6.
BMC Cancer ; 21(1): 1274, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823489

RESUMO

BACKGROUND: The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). METHODS: Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. RESULTS: A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). CONCLUSION: Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

7.
Nat Prod Res ; : 1-6, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758689

RESUMO

A new anthraquinone, asperquinone A (1), and four known anthraquinone derivatives 2-5 were isolated from the mangrove endophytic fungus Aspergillus sp. 16-5C. These structures were elucidated by spectroscopic analysis and the absolute configuration of 1 was unambiguously determined by ECD calculation. Compounds 1-5 showed no significant inhibitory effect against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB).

8.
Cancer Commun (Lond) ; 41(11): 1195-1227, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34699681

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

9.
BMC Public Health ; 21(1): 1961, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715823

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide with continuous rise. Limited studies indicate that COPD was associated with major storms and related power outages (PO). However, significant gaps remain in understanding what PO's role is on the pathway of major storms-COPD. This study aimed to examine how PO mediates the major storms-COPD associations. METHODS: In this time-series study, we extracted all hospital admissions with COPD as the principal diagnosis in New York, 2001-2013. Using distributed lag nonlinear models, the hospitalization rate during major storms and PO was compared to non-major storms and non-PO periods to determine the risk ratios (RRs) for COPD at each of 0-6 lag days respectively after controlling for time-varying confounders and concentration of fine particulate matter (PM2.5). We then used Granger mediation analysis for time series to assess the mediation effect of PO on the major storms-COPD associations. RESULTS: The RRs of COPD hospitalization following major storms, which mainly included flooding, thunder, hurricane, snow, ice, and wind, were 1.23 to 1.49 across lag 0-6 days. The risk was strongest at lag3 and lasted significantly for 4 days. Compared with non-outage periods, the PO period was associated with 1.23 to 1.61 higher risk of COPD admissions across lag 0-6 days. The risk lasted significantly for 2 days and was strongest at lag2. Snow, hurricane and wind were the top three contributors of PO among the major storms. PO mediated as much as 49.6 to 65.0% of the major storms-COPD associations. CONCLUSIONS: Both major storms and PO were associated with increased hospital admission of COPD. PO mediated almost half of the major storms-COPD hospitalization associations. Preparation of surrogate electric system before major storms is essential to reduce major storms-COPD hospitalization.

10.
Elife ; 102021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569932

RESUMO

Accumulating evidence has shown transcranial low-intensity ultrasound can be potentially a non-invasive neural modulation tool to treat brain diseases. However, the underlying mechanism remains elusive and the majority of studies on animal models applying rather high-intensity ultrasound that cannot be safely used in humans. Here, we showed low-intensity ultrasound was able to activate neurons in the mouse brain and repeated ultrasound stimulation resulted in adult neurogenesis in specific brain regions. In vitro calcium imaging studies showed that a specific ultrasound stimulation mode, which combined with both ultrasound-induced pressure and acoustic streaming mechanotransduction, is required to activate cultured cortical neurons. ASIC1a and cytoskeletal proteins were involved in the low-intensity ultrasound-mediated mechanotransduction and cultured neuron activation, which was inhibited by ASIC1a blockade and cytoskeleton-modified agents. In contrast, the inhibition of mechanical-sensitive channels involved in bilayer-model mechanotransduction like Piezo or TRP proteins did not repress the ultrasound-mediated neuronal activation as efficiently. The ASIC1a-mediated ultrasound effects in mouse brain such as immediate response of ERK phosphorylation and DCX marked neurogenesis were statistically significantly compromised by ASIC1a gene deletion. Collated data suggest that ASIC1a is the molecular determinant involved in the mechano-signaling of low-intensity ultrasound that modulates neural activation in mouse brain.


Assuntos
Canais Iônicos Sensíveis a Ácido/metabolismo , Encéfalo/metabolismo , Mecanotransdução Celular , Neurogênese , Neurônios/metabolismo , Ondas Ultrassônicas , Canais Iônicos Sensíveis a Ácido/genética , Animais , Encéfalo/citologia , Células CHO , Sinalização do Cálcio , Cricetulus , Citoesqueleto/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Neuropeptídeos/metabolismo , Fosforilação , Pressão , Fatores de Tempo
11.
Libyan J Med ; 16(1): 1961382, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34357857

RESUMO

How to identify the optimum switch point of sequential invasive and noninvasive ventilation is the focus of clinical attention on the patients suffering from acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated by acute respiratory failure (ARF). This study aims to explore the clinical significance of taking the change rate of procalcitonin (PCT) as identifying the timing of weaning on the mechanical ventilation for the patients of AECOPD followed by ARF as a complication. There were altogether 140 patients of AECOPD complicated with ARF, who were randomly selected and divided into a study group and a control group respectively. A change rate of serum PCT level exceeding 50% was taken as the switch point selection of tracheal intubation removal for the patients of the study group, while the 'pulmonary infection control (PIC) window' was done for those in the control group. With CRP, IL-6, TNF-a, PaCO2, PaO2, and Lac having been detected before and after treatment to them all, clinical indexes were obtained and compared between these two groups. The CRP, TNF-a, and IL-6 levels of the patients in the study group after treatment (p < 0.05) were lower than those in the control group. There was no significant difference in PaCO2, PaO2, and Lac between these two groups before and after treatment (p > 0.05). Even so, some other indexes available for the study group of patients were found to be lower than those for the control group (p < 0.05) in the following aspects: duration of invasive ventilation support, total time of mechanical ventilation support, incidence rate of ventilator-associated pneumonia, 48-hour reintubation rate, incidence rate of upper gastrointestinal bleeding, hospitalization time of critical respiratory illness, total hospitalization time, RICU treatment cost, total treatment cost, and mortality. It is preferable to take the change rate of PCT level exceeding 50% as the switch point of weaning time in sequential mechanical ventilation rather than the PIC window. AbbreviationsAECOPD: acute exacerbation of chronic obstructive pulmonary disease; ARF: acute respiratory failure; PCT: procalcitonin; PaO2: the oxygen partial pressure; PaCO2: the partial pressure of carbon dioxide; TNF-a: serum tumor necrosis factor-a; IL-6: interleukin-6; CRP: serum C-reactive protein; PIC window: pulmonary infection control window; RICU: respiration and intensive care unit.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Insuficiência Respiratória , Humanos , Cinética , Pró-Calcitonina , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/terapia , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia
12.
Ecotoxicol Environ Saf ; 223: 112609, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34385062

RESUMO

OBJECTIVE: By exploring the exposure-response relationships between meteorological factors and rupture of intracranial aneurysm (IA) to reveal the influence of meteorological variation on IA rupture under the specific climate in Fujian, China. METHOD: 7515 cases of IA rupture from several municipal medical institutions in Fujian Province as well as local meteorological data during the same period were collected from 2013 to 2017. Poisson regression and Spearman correlation analysis were applied to explore the distribution characteristics of IA rupture and how it is associated with meteorological parameters. Poisson generalized additive model was established to further analyze the exposure-response relationships between meteorological factors and IA rupture, and its hysteresis effects. RESULT: The IA rupture exhibited a negative correlation with temperature (rs = -0.323, 95% CI: -0.539 ~ -0.068) and a positive correlation with atmospheric pressure (rs = 0.397, 95% CI: 0.152-0.597) or pressure difference (rs = 0.296, 95% CI: 0.038-0.517), 21.05 â„ƒ and 1000.14 hPa were the risk thresholds for the onset ascribed to variation in temperature and atmospheric pressure, respectively. Temperature and atmospheric pressure also exerted hysteresis effects on IA rupture. Cold will increase the rupture risk in the subsequent 1-3 days, and high pressure will raise the morbidity in the next 1-2 days. Besides, drastic variations in temperature and atmospheric pressure were also associated with the higher risk of IA rupture in the next 2 days and 1 day, respectively. CONCLUSION: Temperature and atmospheric pressure have a negative and positive correlation with IA rupture in Fujian, China, respectively. Variation in temperature and atmospheric pressure exert different degrees of hysteresis effects on IA rupture.


Assuntos
Aneurisma Intracraniano , Pressão Atmosférica , China/epidemiologia , Humanos , Incidência , Aneurisma Intracraniano/epidemiologia , Estações do Ano , Temperatura
13.
Sci Total Environ ; 797: 149199, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34346383

RESUMO

BACKGROUND: There is little work in assessing the impact of storm events combined with power outage (PO). In this study, we evaluated the individual and synergistic impacts of wind events and PO on overall and subtypes of injuries in New York State (NYS) and by demographics. METHODS: The emergency department (ED) visit data were obtained from the NYS Department of Health from November-April 2005-2013 to identify injury cases, length of stay and care costs. Wind event was defined according to high wind, strong wind or thunderstorm wind defined by NOAA. PO occurrence was defined when PO coverage exceeded the 50th percentile of its distribution. By comparing non-event days, we used distributed lag nonlinear models to evaluate the impacts of wind events, PO, and their combined effect on injuries during the cold season over a 0-3-day lag period, while controlling for time-varying confounders. The differences in critical care indicators between event and non-event days were also evaluated. RESULTS: Overall injuries ED visits (16,628,812) significantly increased during the wind events (highest Risk Ratio (RR): 1.05; 95% CI: 1.02-1.08), and were highest when wind events cooccurred with PO (highest RR: 1.14; 95% CI: 1.10-1.18), but not during PO alone (RR: 1.00; 95%CI: 0.96-1.04). The increase was also observed with all subgroups through Day 2 after the event. Greater risks exist for older adults (≥65 years) and those on Medicaid. After the joint occurrences of wind events and PO, average visits are 0.2 days longer, and cost 13% more, compared to no wind/no PO days. CONCLUSION: There is a significant increase in ED visits, length of stay and cost of injuries during wind events, especially when they coupled with PO and especially among older cases and Medicaid holders. Our findings may be used for planning disaster preparedness and recovery efforts.


Assuntos
Planejamento em Desastres , Serviço Hospitalar de Emergência , New York/epidemiologia , Estações do Ano , Estados Unidos , Vento
14.
Int J Epidemiol ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34406380

RESUMO

BACKGROUND: Beneficial effects of greenness on birth outcomes have been reported, but few studies have investigated the associations in both urban and non-urban settings. We aimed to evaluate and compare linear and nonlinear associations between greenness and birth outcomes in urban and non-urban settings. METHODS: From October 2015 to December 2018, participants were recruited into the Maoming Birth Cohort Study. A total of 11 258 live birth records were obtained. Greenness exposure was assessed using the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). Linear regression and nonlinear restricted cubic spline models were implemented to investigate the associations between greenness and birthweight, birth length, gestational age, preterm birth, low birthweight, small for gestational age and the potential for effect variation under urban or non-urban settings, after adjusting for covariates. RESULTS: A 0.1-unit increase in NDVI-500m was significantly associated with an increase of 35.4 g in birthweight [95% confidence interval (CI): 13.2, 57.7], 0.15 cm in birth length (95% CI: 0.03, 0.26), 0.88 days in gestational age (95% CI: 0.05, 1.71) and lower odds of low birthweight [odds ratio (OR) = 0.69, 95% CI: 0.56, 0.85] and preterm birth (OR = 0.70, 95% CI: 0.58, 0.85). No association with head circumference was observed. For all outcomes, no significant linear associations were observed among non-urban dwellers. Inversed 'U-shaped' associations between greenness exposure and birth outcomes were observed in the total study population. CONCLUSIONS: Greenness exposure was associated with increased gestational age, birthweight and birth length in urban dwellers. Nonlinear associations assessed by restricted cubic splines suggested that health benefits could be larger when increasing greenness levels from low to medium compared with increasing greenness from medium to high levels. Further studies adopting nonlinear methods are warranted to verify our findings.

15.
Organogenesis ; : 1-13, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34405770

RESUMO

To develop a tissue-engineered vascular graft, we used pericardial effusion-derived progenitor cells (PEPCs) collected from drained fluid after open-heart surgery in children with congenital heart diseases to repopulate a decellularized porcine pulmonary artery. The PEPCs were compared with human fibroblasts (HS68) and human umbilical vein endothelial cells (HUVECs) in cell growth and migration. They were cultured with the matrices via an inner approach (intima), lateral approach (media), and outer approach (adventitia). PEPCs grew and migrated better than the other two cells 14 days after seeding in the decellularized vessel. In immunofluorescence assays, PEPCs expressed CD90 and CD105 indicating a vascular differentiation. PEPCs grew in a decellularized porcine pulmonary artery matrix may have the potential for producing tissue-engineered vascular grafts.

16.
Life (Basel) ; 11(8)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34440469

RESUMO

This study aimed to examine effect modification of maternal risk factor exposures and congenital heart disease (CHD) by maternal folic acid supplementation (FAS)/non-FAS. We included 8379 CHD cases and 6918 CHD-free controls from 40 clinical centers in Guangdong Province, Southern China, 2004-2016. Controls were randomly chosen from malformation-free fetuses and infants and frequency matched to the echocardiogram-confirmed cases by enrollment hospital and year of birth. We used multiple regression models to evaluate interactions between FAS/non-FAS and risk factors on CHDs and major CHD categories, adjusted for confounding variables. We detected statistically significant additive and multiplicative interactions between maternal FAS/non-FAS and first-trimester fever, viral infection, and threatened abortion on CHDs. An additive interaction on CHDs was also identified between non-FAS and living in a newly renovated home. We observed a statistically significant dose-response relationship between non-FAS and a greater number of maternal risk factors on CHDs. Non-FAS and maternal risk factors interacted additively on multiple critical CHDs, conotruncal defects, and right ventricular outflow tract obstruction. Maternal risk factor exposures may have differential associations with CHD risk in offspring, according to FAS. These findings may inform the design of targeted interventions to prevent CHDs in highly susceptible population groups.

17.
Environ Sci Technol ; 55(14): 10035-10045, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34232029

RESUMO

Understanding potential health risks associated with biofuel production is critical to sustainably combating energy insecurity and climate change. However, the specific health impacts associated with biorefinery-related emissions are not yet well characterized. We evaluated the relationship between respiratory emergency department (ED) visits (2011-2015) and residential exposure to biorefineries by comparing 15 biorefinery sites to 15 control areas across New York (NY) State. We further examined these associations by biorefinery types (e.g., corn, wood, or soybean), seasons, and lower respiratory disease subtypes. We measured biorefinery exposure using residential proximity in a cross-sectional study and estimation of biorefinery emission via AERMOD-simulated modeling. After controlling for multiple confounders, we consistently found that respiratory ED visit rates among residents living within 10 km of biorefineries were significantly higher (rate ratios (RRs) range from 1.03 to 3.64) than those in control areas across our two types of exposure indices. This relationship held across biorefinery types (higher in corn and soybean biorefineries), seasons (higher in spring and winter), air pollutant types (highest for NO2), and respiratory subtypes (highest for emphysema). Further research is needed to confirm our findings.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos Transversais , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , New York/epidemiologia , Material Particulado/análise
18.
Medicine (Baltimore) ; 100(27): e26555, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232197

RESUMO

BACKGROUND: The patient suffering from urinary sepsis is often accompanied by elevated serum procalcitonin (PCT) levels and a decline in the average platelet count (PLT), which could result in a poor prognosis. This study aimed to evaluate the value of PCT and PLT in determining the severity of urinary sepsis. METHODS: A total of 120 urosepsis patients enrolled were divided into a survival group and a death group, respectively, according to their status within 14 days after admission. Changes in PCT and PLT levels between the 2 groups were compared at different time points. A receiver operating characteristic (ROC) curve was eventually obtained to predict the prognostic value of PCT and PLT. RESULTS: The PCT levels in the survival group declined gradually after admission, and the PLT decreased at first but increased rapidly in subsequence. The PCT level in the death group, however, declined in a flat-slope trend or was hardly noticeable together with the number of PLT reduced significantly. In particular, it is on the 3rd day that PCT tended to positively correlate with acute physiological and chronic health score II (APACHE II) score (r = 0.730, P < .05), but negatively with PLT (r = 0.472, P < .05). The APACHE II score and PLT (r = 0.612, P < .05) were also negatively correlated with each other. As indicated by the ROC curve, the PCT level on the 3rd day after admission was of great value for the clinical mortality prognosis, and the area under the curve was 0.858. Moreover, PLT also has a high predictive value for prognosis. Area under the curve is 0.951. When the PLT was more than 51 × 109 /L, the sensitivity was up to 90%, and the specificity was 90%. CONCLUSION: PLT and PCT levels are closely related to the APACHE II score, which could indicate the severity of urosepsis in patients. The contribution of this study was to confirm that dynamic monitoring of the changes in PCT and PLT helps determine the prognosis of urosepsis patients.


Assuntos
Plaquetas/patologia , Pró-Calcitonina/sangue , Sepse/sangue , Infecções Urinárias/sangue , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Sepse/etiologia , Infecções Urinárias/etiologia
19.
Pain Physician ; 24(5): E573-E581, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34323444

RESUMO

BACKGROUND: Mechanical compression on the trigeminal root entry zone (TREZ) by microvascular is the main etiology of primary trigeminal neuralgia (TN). OBJECTIVES: To study the pathogenesis of TN, hub genes screening in the TREZ of TN in an animal model was performed. STUDY DESIGN: A double blind, randomized study was designed in a controlled animal trial. SETTING: The research took place in the Laboratory of Clinical Applied Anatomy at the School of Basic Medical Science of Fujian Medical University. METHODS: Twelve male rats were randomly divided into a sham operation group and a TN animal model group. TN animal model was induced by chronic compression of trigeminal nerve root (CCT) operation. Gene expression in the TREZ were analyzed by RNA sequencing (RNA-Seq) technique. KEGG analysis, GO analysis, and PPI analysis were performed in the DEGs. Key signaling pathways analyzing by GSEA and the hub genes in the DEGs were also studied. Reverse transcription real-time polymerase chain reaction (RT-qPCR) was used to verify the RNA-Seq results. RESULTS: Transcriptome data showed that 352 genes up-regulated and 59 genes down-regulated in DEGs on post-operation day 21, after CCT operation in the TN group. KEGG analysis revealed that, "neuroactive ligand receptor interaction" and "cytokine cytokine receptor interaction" may be related to the pathogenesis of TN. GO analysis showed "regulation of signing receptor activity", "chemokine activity", and "carbohydrate binging" may be related to TN. The RT-qPCR results were consistent with the test results, indicating that the transcriptome sequencing results were reliable. LIMITATIONS: Although the incidence of TN in female rats was higher than in male rats, we only used male SD rats to establish the TN animal model, to avoid the effect of estrogen on experimental results. This study only presents some respects of RNA-Seq technique and, therefore, did not identify the DEGs at the protein level. The relationship between the DEGs at different levels shoud be done in the future. CONCLUSIONS: Based on the results of RNA-seq, this study discovered 6 hub genes in the TREZ that are closely related to the TN animal model, which provide a potential breakthrough point to explore the pathogenesis of TN.


Assuntos
Neuralgia do Trigêmeo , Animais , Modelos Animais de Doenças , Feminino , Masculino , RNA-Seq , Ratos , Ratos Sprague-Dawley , Nervo Trigêmeo
20.
J Chin Med Assoc ; 84(8): 791-794, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074932

RESUMO

BACKGROUND: Post-dural puncture headache (PDPH) is the most common complication of lumbar puncture. Patients who received lumbar puncture were previously suggested to remain in bed for a certain time to prevent PDPH; however, this concept was challenged by recent studies. We aimed to investigate whether ambulation instead of resting supine following lumbar puncture could increase the risk of PDPH. METHODS: The study used a prospective cohort design, applying convenience sampling among patients who received diagnostic lumbar puncture between January and September 2018 in the neurology ward of a tertiary medical center. The patients who fulfilled the inclusion criteria were informed that the current practice suggests lying supine for 6 to 8 hours after lumbar puncture, but they were allowed to either follow the suggestion or ambulate by their wills. The timing of bed rest was recorded, in addition to other possible risk factors of PDPH. The study endpoint is the presence or absence of PDPH within 48 hours of lumbar puncture. RESULTS: A total of 137 patients who received lumbar puncture were enrolled, including 103 with bed rest following lumbar puncture and 34 without. There was no difference in demographics between the two groups. PDPH was found in 21 patients, with a total follow-up period of 5959 person-hours and an incidence density of 0.35%. There was no significant difference between the incidence of PDPH between the two groups (non-bed rest group 5.9% vs bed rest group 18.4%; p = 0.078), nor was incidence density (non-bed rest group 0.13% vs bed rest group 0.43%, p = 0.113). The results remained the same after adjusting for age. CONCLUSION: Bed rest following lumbar puncture does not prevent PDPH, and even leads to a marginally increased risk of PDPH. Amendment to the current practice guideline post-lumbar puncture care might be needed to improve patient care.

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