RESUMO
Formaldehyde (HCHO) is an important source for driving tropospheric ozone (O3) formation. This study investigated the combined effects of anthropogenic and biogenic emission on O3 formation in the Guanzhong Basin (GZB), Central China, providing useful information into the mechanisms of O3 formation due to the interaction between anthropogenic and biogenic volatile organic compounds (VOCs). A severe O3 pollution episode in summer of 2017 was simulated using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) to examine the impacts of ambient HCHO on ground-level O3. Results showed secondary HCHO dominated ambient levels, peaking in the afternoon (up to 86 %), while primary emissions contributed 14 % on average. This enhanced O3 production by 7.7 % during the morning rush hour and 24.3 % in the afternoon. In addition, HCHO concentration peaked before that of O3, suggesting it plays significant role in O3 formation. Biogenic emission oxidation contributed 3.1 µg m-3 (53.1 %) of HCHO and 5.2 pptv (40.1 %) of hydroperoxyl radicals (HO2) in average urban areas, where the downwind regions of the forests had high nitrogen oxides (NOx) levels and favorable conditions for O3 production (17.3 µg m-3, 20.5 %). In forested regions, sustained isoprene oxidation led to elevated oxidized VOCs including HCHO and acetaldehyde downwind, which practiced further photolysis of O3 formation with anthropogenic NOx in urban areas. Sensitivity experiments recommend controlling industrial and traffic NOx emissions, with regional joint prevention and regulation, which are essential to reduce O3 pollution.
Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Formaldeído , Ozônio , Compostos Orgânicos Voláteis , Formaldeído/análise , Poluentes Atmosféricos/análise , China , Ozônio/análise , Compostos Orgânicos Voláteis/análise , Florestas , Poluição do Ar/estatística & dados numéricosRESUMO
Deoxynivalenol (DON) is a mycotoxin produced by Fusarium graminearum, and curcumin (CUR) is a natural polyphenolic compound found in turmeric. However, the combined treatment of CUR and DON to explore the mitigating effect of CUR on DON and their combined mechanism of action is not clear. Therefore, in this study, we established four treatment groups (CON, CUR, DON and CUR + DON) to investigate their mechanism in the porcine intestinal epithelial cells (IPEC-J2). In addition, the cross-talk and alleviating potential of CUR interfering with DON-induced cytotoxic factors were evaluated by in vitro experiments; the results showed that CUR could effectively inhibit DON-exposed activated TNF-α/NF-κB pathway, attenuate DON-induced apoptosis, and alleviate DON-induced endoplasmic reticulum stress and oxidative stress through PERK/CHOP pathways, which were verified at both mRNA and protein levels. In conclusion, these promising findings may contribute to the future use of CUR as a novel feed additive to protect livestock from the harmful effects of DON.
Assuntos
Apoptose , Curcumina , Estresse do Retículo Endoplasmático , Tricotecenos , Tricotecenos/farmacologia , Tricotecenos/toxicidade , Animais , Curcumina/farmacologia , Suínos , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Linhagem Celular , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The frequently encountered wastewater contaminations, including soluble aromatic compound and dye pollutants, pathogenic bacteria, and insoluble oils, have resulted in significant environmental and human health issues. It poses a challenge to utilize identical materials for the treatment of complex wastewater. Herein, in this research, multifunctional Ag NPs/guar gum hybrid hydrogels were fabricated using a facile in situ reduction and self-crosslinking method for efficient remediation of complex wastewater. The Ag NPs/guar gum hybrid hydrogel showed remarkable remodeling, adhesive, and self-healing characteristics, which was favorable for its versatile applications. The combination of Ag NPs with the guar gum skeleton endowed the hybrid hydrogel with exceptional catalytic activity for reducing aromatic compounds and dye pollutants, as well as remarkable antibacterial efficacy against pathogenic bacteria. In addition, the Ag NPs/guar gum hybrid hydrogel could be employed to coat a variety of substrates, including cotton fabrics and stainless steel meshes. The hydrogel coated cotton fabrics and meshes presented superhydrophilicity/underwater superoleophobicity, excellent antifouling capacity, and outstanding recyclability, which could be successfully applied for efficient separation of oil-water mixtures. The findings of this work provide a feasible and cost-effective approach for the remediation of intricate wastewater.
Assuntos
Antibacterianos , Galactanos , Hidrogéis , Mananas , Nanopartículas Metálicas , Gomas Vegetais , Prata , Galactanos/química , Gomas Vegetais/química , Prata/química , Mananas/química , Antibacterianos/química , Antibacterianos/farmacologia , Catálise , Nanopartículas Metálicas/química , Hidrogéis/química , Águas Residuárias/química , Purificação da Água/métodos , Água/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Óleos/químicaRESUMO
Based on the data of the State of Global Air (2020), air quality deterioration in Thailand has caused ~32,000 premature deaths, while the World Health Organization evaluated that air pollutants can decrease the life expectancy in the country by two years. PM2.5 was collected at three air quality observatory sites in Chiang-Mai, Bangkok, and Phuket, Thailand, from July 2020 to June 2021. The concentrations of 25 elements (Na, Mg, Al, Si, S, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Se, Br, Sr, Ba, and Pb) were quantitatively characterised using energy-dispersive X-ray fluorescence spectrometry. Potential adverse health impacts of some element exposures from inhaling PM2.5 were estimated by employing the hazard quotient and excess lifetime cancer risk. Higher cancer risks were detected in PM2.5 samples collected at the sampling site in Bangkok, indicating that vehicle exhaust adversely impacts human health. Principal component analysis suggests that traffic emissions, crustal inputs coupled with maritime aerosols, and construction dust were the three main potential sources of PM2.5. Artificial neural networks underlined agricultural waste burning and relative humidity as two major factors controlling the air quality of Thailand.
Assuntos
Poluentes Atmosféricos , Neoplasias , Humanos , Análise de Componente Principal , Monitoramento Ambiental , Tailândia , Poluentes Atmosféricos/análise , Poeira/análise , Análise de Regressão , Material Particulado/análiseRESUMO
Polycyclic aromatic hydrocarbons (PAHs) in urban fugitive dust, known for their toxicity and ability to generate reactive oxygen species (ROS), are a major public health concern. This study assessed the spatial distribution and health risks of 15 PAHs in construction dust (CD) and road dust (RD) samples collected from June to November 2021 over the cities of Tongchuan (TC), Baoji (BJ), Xianyang (XY), and Xi'an (XA) in the Guanzhong Plain, China. The average concentration of ΣPAHs in RD was 39.5 ± 20.0 µg g-1, approximately twice as much as in CD. Four-ring PAHs from fossil fuels combustion accounted for the highest proportion of ΣPAHs in fugitive dust over all four cities. Health-related indicators including benzo(a)pyrene toxic equivalency factors (BAPTEQ), oxidative potential (OP), and incremental lifetime cancer risk (ILCR) all presented higher risk in RD than those in CD. The multilayer perceptron neural network algorithm quantified that vehicular and industrial emissions contributed 86 % and 61 % to RD and CD BAPTEQ, respectively. For OP, the sources of biomass and coal combustion were the key generator which accounted for 31-54 %. These findings provide scientific evidence for the direct efforts toward decreasing the health risks of fugitive dust in Guanzhong Plain urban agglomeration, China.
Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Poeira/análise , Monitoramento Ambiental , Medição de Risco , China , Cidades , Redes Neurais de Computação , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análiseRESUMO
Zearalenone (ZEA) is a mycotoxin with an estrogen-like effect that is widely found in feed. Lipopolysaccharides (LPS) derived from Gram-negative bacteria are a common endotoxin, and both toxins have effects on human and livestock health. During animal feeding, ZEA as an exotoxin and LPS as an endotoxin have the potential to co-exist in organisms. At present, other studies have only focused on the hazards of single toxins, but there are fewer studies on the coexistence and interaction between ZEA and LPS. Therefore, a further study to investigate the combined toxic effects of different concentrations of ZEA and LPS is warranted. Quercetin (QUE) is a natural flavonoid compound with strong antioxidant and anti-inflammatory properties. It is unclear whether QUE can mitigate the combined effects of ZEA and LPS. IPEC-J2, isolated from the jejunum of non-breastfed neonatal piglets, is an ideal model for the study of epithelial cell transport, intestinal bacterial interactions, and the nutrient modulation of intestinal function. Therefore, the purpose of the present study was to demonstrate the effect of QUE in alleviating the combined toxic effect of ZEA and LPS on IPEC-J2 cell damage. Cell viability was measured after treating IPEC-J2 cells sequentially with 10, 20, 30, 40, 60, 80, and 100 µM ZEA, 1, 10, 50, and 100 µg/mL LPS, and 20, 40, 60, 80, 100, and 200 µM QUE for 24 h. Based on the cell viability results, 20 µM ZEA and 1 µg/mL LPS were selected as the most suitable concentrations for further analysis. For QUE, 20 µM increased the cell viability, while 40-200 µM QUE decreased the cell viability. Therefore, for the subsequent study, 20 µM QUE was selected in combination with 20 µM ZEA and 1 µg/mL LPS. The results showed that QUE increased the cellular viability and decreased the LDH content more compared to the effects of the ZEA+LPS group. At the gene level, QUE addition up-regulated the expression of Nrf2, HO-1, SOD2, and NQO1 at the gene or protein level compared to those of the ZEA+LPS group. The measurement of tight junction-related genes and proteins showed QUE up-regulated the expression of Claudin, ZO-1, and Occludin genes and proteins more than in the ZEA+LPS group. QUE addition reduced the rate of apoptosis more than that in the ZEA+LPS group. The expressions of Bcl-2 and Bax were examined at the gene level, and QUE addition significantly reduced the Bax gene expression level compared to that of the ZEA+LPS group, but there was no apparent variation in the expression level of Bcl-2. In summary, QUE can alleviate the combined toxic effects of ZEA and LPS on IPEC-J2 cells via modulating the Nrf2 signaling pathway, up-regulating the expression of antioxidative genes, and enhancing the intestinal barrier.
Assuntos
Zearalenona , Humanos , Animais , Suínos , Zearalenona/metabolismo , Quercetina/farmacologia , Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Linhagem Celular , Transdução de Sinais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Células EpiteliaisRESUMO
BACKGROUND: Small cell lung cancer (SCLC) is a highly malignant cancer characterized by metastasis and an extremely poor prognosis. Although combined chemoimmunotherapy improves the prognosis of extensive-stage (ES)-SCLC, the survival benefits remain limited. Furthermore, no reliable biomarker is available so far to predict the treatment outcomes for chemoimmunotherapy. METHODS: This retrospective study included patients with ES-SCLC treated with first-line combined atezolizumab or durvalumab with standard chemotherapy between Janauray 1, 2019 and October 1, 2022 at five medical centers in China as the chemoimmunotherapy group. The patients were divided into one training cohort and two independent external validation cohorts. Additionally, we created a control group of ES-SCLC who was treated with first-line standard chemotherapy alone. The Radiomics Score was derived using machine learning algorithms based on the radiomics features extracted in the regions of interest delineated on the chest CT obtained before treatment. Cox proportional hazards regression analysis was performed to identify clinical features associated with therapeutic efficacy. The log-rank test, time-dependent receiver operating characteristic curve, and Concordance Index (C-index) were used to assess the effectiveness of the models. RESULTS: A total of 341 patients (mean age, 62±8.7 years) were included in our study. After a median follow-up time of 12.1 months, the median progression-free survival (mPFS) was 7.1 (95% CI 6.6 to 7.7) months, whereas the median overall survival (mOS) was not reached. The TNM stage, Eastern Cooperative Oncology Group performance status, and Lung Immune Prognostic Index showed significant correlations with PFS. We proposed a predictive model based on eight radiomics features to determine the risk of chemoimmunotherapy resistance among patients with SCLC (validation set 1: mPFS, 12.0 m vs 5.0 m, C-index=0.634; validation set 2: mPFS, 10.8 m vs 6.1 m, C-index=0.617). By incorporating the clinical features associated with PFS into the radiomics model, the predictive efficacy was substantially improved. Consequently, the low-progression-risk group exhibited a significantly longer mPFS than the high-progression-risk group in both validation set 1 (mPFS, 12.8 m vs 4.5 m, HR=0.40, p=0.028) and validation set 2 (mPFS, 9.2 m vs 4.6 m, HR=0.30, p=0.012). External validation set 1 and set 2 yielded the highest 6-month area under the curve and C-index of 0.852 and 0.820, respectively. Importantly, the integrated prediction model also exhibited considerable differentiation power for survival outcomes. The HR for OS derived from the low-progression-risk and high-progression-risk groups was 0.28 (95% CI 0.17 to 0.48) in all patients and 0.20 (95% CI 0.08 to 0.54) in validation set. By contrast, no significant differences were observed in PFS and OS, between high-progression-risk patients receiving chemoimmunotherapy and the chemotherapy cohort (mPFS, 5.5 m vs 5.9 m, HR=0.90, p=0.547; mOS, 14.5 m vs 13.7 m, HR=0.97, p=0.910). CONCLUSIONS: The integrated clinical and radiomics model can predict the treatment outcomes in patients with ES-SCLC receiving chemoimmunotherapy, rendering a convenient and low-cost prognostic model for decision-making regarding patient management.
Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Pessoa de Meia-Idade , Idoso , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Imunoterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
BACKGROUND: This study aimed to describe the clinical characteristics and analyze the poor prognostic factors in patients with anti-MDA5 dermatomyositis. METHODS: A total of 126 adults with anti-MDA5 dermatomyositis were enrolled in this retrospective study. Information on survival time, cause of death, and baseline characteristics was collected. Patients were divided into two groups: a survival group and a non-survival group. Items with clinical significance that showed significant differences between the two groups were screened by Kaplan-Meier and Cox regression analyses to identify the predictors of poor survival. RESULTS: Thirty-two patients were included in the non-survival group, most of whom died from respiratory failure, with pulmonary infection accounting for half. Epstein-Barr virus infection was relatively common in both groups. Aspartate transaminase, lactate dehydrogenase, and ferritin levels; erythrocyte sedimentation rate; and anti-Ro52 antibody levels were significantly higher, while the lymphocyte count was lower in the non-survival group compared with the survival group. Notably, patients in the non-survival group were more likely to present with rapidly progressive interstitial lung disease than those in the survival group. Kaplan-Meier and Cox multivariate regression analyses revealed that the prevalence of rapidly progressive interstitial lung disease, levels of anti-Ro52 antibody, and age > 57 years were important prognostic factors independent of multiple clinical parameters. CONCLUSIONS: Rapidly progressive interstitial lung disease, anti-Ro52 antibody levels, and age > 57 years are possible predictors of mortality risk in patients with anti-MDA5 dermatomyositis.
Assuntos
Dermatomiosite , Infecções por Vírus Epstein-Barr , Doenças Pulmonares Intersticiais , Adulto , Humanos , Pessoa de Meia-Idade , Herpesvirus Humano 4 , Estudos RetrospectivosRESUMO
Objective: To evaluate the effectiveness of limited internal fixation combined with a hinged external fixator in the treatment of peri-elbow bone infection. Methods: The clinical data of 19 patients with peri-elbow bone infection treated with limited internal fixation combined with a hinged external fixator between May 2018 and May 2021 were retrospectively analyzed. There were 15 males and 4 females with an average age of 44.6 years (range, 28-61 years). There were 13 cases of distal humerus fractures and 6 cases of proximal ulna fractures. All the 19 cases were infected after internal fixation of fracture, and 2 cases were complicated with radial nerve injury. According to Cierny-Mader anatomical classification, 11 cases were type â ¡, 6 cases were type â ¢, and 2 cases were type â £. The duration of bone infection was 1-3 years. After primary debridement, the bone defect was (3.04±0.28) cm, and the antibiotic bone cement was implanted into the defect area, and the external fixator was installed; 3 cases were repaired with latissimus dorsi myocutaneous flap, and 2 cases were repaired with lateral brachial fascial flap. Bone defects repair and reconstruction were performed after 6-8 weeks of infection control. The wound healing was observed, and white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reaction protein (CRP) were reexamined regularly after operation to evaluate the infection control. X-ray films of the affected limb were taken regularly after operation to observe the bone healing in the defect area. At last follow-up, the flexion and extension range of motion and the total range of motion of the elbow joint were observed and recorded, and compared with those before operation, and the function of the elbow joint was evaluated by Mayo score. Results: All patients were followed up 12-34 months (mean, 26.2 months). The wounds healed in 5 cases after skin flap repair. Two cases of recurrent infection were effectively controlled by debridement again and replacement of antibiotic bone cement. The infection control rate was 89.47% (17/19) in the first stage. Two patients with radial nerve injury had poor muscle strength of the affected limb, and the muscle strength of the affected limb recovered from grade â ¢ to about grade â £ after rehabilitation exercise. During the follow-up period, there was no complication such as incision ulceration, exudation, bone nonunion, infection recurrence, or infection in the bone harvesting area. Bone healing time ranged from 16 to 37 weeks, with an average of 24.2 weeks. WBC, ESR, CRP, PCT, and elbow flexion, extension, and total range of motions significantly improved at last follow-up ( P<0.05). According to Mayo elbow scoring system, the results were excellent in 14 cases, good in 3 cases, and fair in 2 cases, and the excellent and good rate was 89.47%. Conclusion: Limited internal fixation combined with a hinged external fixator in the treatment of the peri-elbow bone infection can effectively control infection and restore the function of the elbow joint.
Assuntos
Articulação do Cotovelo , Fraturas Ósseas , Masculino , Feminino , Humanos , Adulto , Cotovelo , Articulação do Cotovelo/cirurgia , Estudos Retrospectivos , Cimentos Ósseos , Resultado do Tratamento , Fixadores Externos , Fixação Interna de Fraturas/métodos , Amplitude de Movimento ArticularRESUMO
BACKGROUND: Esophageal neuroendocrine carcinoma (NEC) is a rare cancer with an extremely poor prognosis. The average overall survival of patients with metastatic disease is only 1 year. The efficacy of anti-angiogenic agents combined with immune checkpoint inhibitors remains unknown. CASE PRESENTATION: A 64-year-old man, initially diagnosed with esophageal NEC, underwent neoadjuvant chemotherapy and esophagectomy. Although the patient remained disease-free for 11 months, eventually the tumor progressed and did not respond to three lines of combined therapy (etoposide plus carboplatin with local radiotherapy, albumin-bound paclitaxel plus durvalumab, and irinotecan plus nedaplatin). The patient then received anlotinib plus camrelizumab, and a dramatic regression was observed (confirmed by positron emission tomography-computed tomography). The patient has been disease-free for over 29 months and has survived for over 4 years since diagnosis. CONCLUSION: Combined therapy with anti-angiogenic agents and immune checkpoint inhibitors may be a promising strategy for esophageal NEC, although more evidence is warranted to validate its efficacy.
Assuntos
Carcinoma Neuroendócrino , Neoplasias Esofágicas , Masculino , Humanos , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/patologia , Carboplatina/uso terapêutico , Carcinoma Neuroendócrino/patologiaRESUMO
Tire and road wear microplastics (TRWMPs) are one of the main non-exhaust pollutants of motor vehicles, which cause serious environmental and health issues. Here, TRWMPs in PM2.5 samples were collected in a tunnel in urban Xi'an, northwest China, during four periods [I: 7:30-10:30, II: 11:00-14:00, III: 16:30-19:30, IV: 20:00-23:00 local standard time (LST)] in summer of 2019. The chemical components of rubbers, benzothiazoles, phthalates, and amines in TRWMPs were quantified, with a total concentration of 6522 ± 1455 ng m-3 (mean ± standard deviation). Phthalates were predominant in TRWMPs, accounting for 64.8% on average, followed by rubbers (33.2%) and benzothiazoles (1.19%). The diurnal variations of TRWMPs showed the highest concentration in Period III (evening rush hour) and the lowest concentration in Period I (morning rush hour), which were not exactly consistent with the variation of the number of light-duty vehicles passed through the tunnel. The result implied that the number of vehicles might not be the most important contributor to TRWMPs concentration, whereas meteorological variables (i.e., precipitation, and relative humidity), vehicle speed, vehicle class, and road cleaning also affected their abundances. The non-carcinogenic risk of TRWMPs in this study was within the international safety threshold, but their carcinogenic risk exceeded the threshold by 2.7-4.6 times, mostly dominated by bis(2-ethylhexyl)phthalate (DEHP). This study provides a new basis for the source apportionment of urban PM2.5 in China. The high concentrations and high potential cancer risks of TRWMPs represent the requirement for more efficient measures to control light-duty vehicle emissions.
Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Material Particulado/análise , Microplásticos , Plásticos , Monitoramento Ambiental , Emissões de Veículos/análise , China , Veículos Automotores , BenzotiazóisRESUMO
Upon myocardial infarction (MI), activated cardiac fibroblasts (CFs) begin to remodel the myocardium, leading to cardiac fibrosis and even heart failure. No therapeutic approaches are currently available to prevent the development of MI-induced pathological fibrosis. Most pharmacological trials fail from poor local drug activity and side effects caused by systemic toxicity, largely due to the lack of a heart-targeted drug delivery system that is selective for activated CFs. Here, we developed a reduced glutathione (GSH)-responsive nanoparticle platform capable of targeted delivering of drugs to activated CFs within the infarct area of a post-MI heart. Compared with systemic drug administration, CF-targeted delivery of PF543, a sphingosine kinase 1 inhibitor identified in a high-throughput antifibrotic drug screening, had higher therapeutic efficacy and lower systemic toxicity in a MI mouse model. Our results provide a CF-targeted strategy to deliver therapeutic agents for pharmacological intervention of cardiac fibrosis.
Assuntos
Cisteína , Infarto do Miocárdio , Camundongos , Animais , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Miocárdio/patologia , Fibrose , Fibroblastos , Modelos Animais de DoençasRESUMO
Met proto-oncogene exon 14 skipping (METex14) mutations are targetable driver genes in approximately 3% of non-small-cell lung cancers (NSCLCs). Ensartinib, a type Ia MET inhibitor, is a multi-kinase inhibitor that has been approved for ALK-positive NSCLCs. Ensartinib was administered for compassionate use (cohort 1) and in a phase II clinical trial (cohort 2) to patients with METex14 mutant NSCLCs, with ORR as a primary endpoint. Molecular simulation was conducted to evaluate ensartinib c-MET interaction, and cell lines, patient-derived organoids (PDOs), and xenograft models were used to test the effectiveness of ensartinib. Among 29 evaluable patients, the ORR and DCR of ensartinib were 67% and 94% in cohort 1, and 73% and 91% in cohort 2. The median DoR was 6.8 months and median PFS was 6.1 months in the total population. Rash was the most common drug-related adverse event, and peripheral edema of any grade was reported in only 9% patients. Molecular simulations indicated favorable binding of ensartinib to c-MET. The kinase assay demonstrated an IC50 of 7.9 nM of ensartinib against METex14 protein. In vitro, Hs746T (METex14 mutation) and EBC-1 (MET amplification) cells were sensitive to ensartinib, with IC50 values of 31 and 44 nM, respectively. Ensartinib exhibited comparable inhibitory effects on cell migration as crizotinib and tepotinib in both cell types. In vivo, ensartinib suppressed the growth of Hs746T cells. Ensartinib also potently inhibited the viability of PDOs. Overall, Ensartinib exhibited substantial antitumor effects against METex14 mutant NSCLCs in preclinical and clinical trials, with relatively low peripheral edema rates.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe , Éxons , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-met/genética , AnimaisRESUMO
PURPOSE: Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO classification of tumors of the central nervous system (CNS WHO), 5th edition, rates PXAs as grade 2 and grade 3. The histological grading was based on mitotic activity (≥2.5 mitoses/mm2). This study specifically evaluates the clinical, morphological, and, especially, the molecular characteristics of grade 2 and 3 PXAs. METHODS: Between 2003 and 2021, we characterized 53 tumors with histologically defined grade 2 PXA (n = 36, 68%) and grade 3 PXA (n = 17, 32%). RESULTS: Compared with grade 2 PXA, grade 3 PXA has a deeper location and no superiority in the temporal lobe and is more likely to be accompanied by peritumoral edema. In histomorphology, epithelioid cells and necrosis were more likely to occur in grade 3 PXA. Molecular analysis found that the TERT promoter mutation was more prevalent in grade 3 PXA than in grade 2 PXA (35% vs. 3%; p = 0.0005) and all mutation sites were C228T. The cases without BRAF V600E mutation or with necrosis in grade 3 PXA had a poor prognosis (p = 0.01). CONCLUSION: These data define PXA as a heterogeneous astrocytoma. Grade 2 and grade 3 PXAs have different clinical and histological characteristics as well as distinct molecular profiles. TERT promoter mutations may be a significant genetic event associated with anaplastic progression. Necrosis and BRAF V600E mutation play an important role in the prognosis of grade 3 PXA.
Assuntos
Astrocitoma , Proteínas Proto-Oncogênicas B-raf , Criança , Adulto Jovem , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Astrocitoma/genética , Astrocitoma/patologia , Mutação , PrognósticoRESUMO
To better respond to heavy air pollution, the local government of Baoji City, a traditionally industry dominated city in northwest China, released several warning levels between December 2019 and January 2020. The system aims to provide a more efficient control of pollution sources. In this study, a high-time resolution measurement of PM2.5-bound elements was applied to capture the diurnal-scale dynamic processes associated with major pollution activities in northwest China. A series of elements were quantified and used for source apportionment using the positive matrix factorization (PMF) model. Combined with the local characteristics, nine sources were resolved with contributions in descending order: fugitive dust (36.6 %), biomass burning (20.1 %), traffic-related (10.4 %), coal combustion (10.0 %), titanium alloy smelting (7.2 %), As-related industry (6.9 %), Zn-related industry (5.6 %), molybdenum alloy smelting (2.5 %), and Cr-related industry (0.7 %). The health risk assessment indicated non-carcinogenic risks for Mn and carcinogenic risks for As and Cr in both adults and children. The cumulative non-carcinogenic risk for the elements was 3.2 times the safety threshold, while the carcinogenic risk (CR) was 6.8 and 27 times the acceptable levels for children and adults, respectively. For source-resolved risks, As- and Cr-related industry emissions showed the highest carcinogenic risk. Five of the nine resolved sources for adults have CR values 1.4 and 9.7 times the acceptable level. This study provides valuable information for developing targeted strategies to control air pollutants and protect public health.
Assuntos
Poluentes Atmosféricos , Criança , Adulto , Humanos , Poluentes Atmosféricos/análise , Poeira/análise , China , Medição de Risco , Ligas , Monitoramento Ambiental , Material Particulado/análiseRESUMO
In this study, the environmental fate of carcinogenic polycyclic aromatic hydrocarbons (PAHs) in tropical lake sediments and their potential sources have been discussed. 15 PAHs (i.e. ΣPAH) have been investigated in two lakes, namely Songkhla Lake (SKL) and Nong Han Kumphawapi Lake (NHL), which are located at the southern and north-eastern parts of Thailand, respectively. Since these two lakes are registered as important wetlands under the Ramsar convention (United Nations Educational, Scientific and Cultural Organization: UNESCO), the quantitative identification of potential contributors of PAHs is an inevitable analytical tool for launching an evidence-based policy. The ΣPAH concentrations observed in SKL and NHL sediments (n = 135) were in the range of 19.4-1,218 ng g-1 and 94.5-1,112 ng g-1, respectively. While the exponential decline of ΣPAH contents were detected in SKL sediments, NHL showed a trend of enhancing PAH contents with depth. The averaged benzo [a]pyrene (B [a]P) contents of surface sediments in both lakes were much below the value stipulated by the United States Environmental Protection Agency (US-EPA) guidelines for carcinogen risk assessment. Based on numerous multivariate statistical techniques coupled with source apportionment analysis, "biomass burning" and "anthropogenic activities" are two potential contributors of the PAHs detected in the study areas. To achieve the long-term conservation of nature with related ecosystem services and cultural values, it is therefore important to promote decision-making based on ecotoxicological studies of carcinogenic substances.
RESUMO
Baoji is a typical heavy industrial city in northwest China. Its air quality is greatly impacted by the emission from the factories. Elements in fine particulate matter (PM2.5) that are greatly emitted from anthropogenic sources could pose diverse health impacts on humans. In this study, an online AMMS-100 atmospheric heavy metal analyzer was used to quantify 30 elements in PM2.5 under the weak and strong anthropogenic disturbance scenarios before the city lockdown period (from January 9th to 23rd) and the lockdown period (from January 26th to February 9th) due to the outbreak of COVID-19 in 2020. During the lockdown period, the average total concentration of total quantified elements was 3475.0 ng/m3, which was 28% and 33% lower than that of the week and strong anthropogenic disturbance scenarios during the pre-lockdown period. The greatest reductions were found for the elements of chromium (Cr), titanium (Ti), manganese (Mn), and Zinc (Zn), consistent with the industrial structure of Baoji. The mass concentrations of most elements showed obvious reductions when the government post-alerted the industries to reduce the operations and production. Dust, traffic sources, combustion, non-ferrous metal processing, and Ti-related industrial processing that are the contributors of the elements in the pre-lockdown period were apportioned by the positive matrix factorization (PMF) model. Substantial changes in the quantified elements' compositions and sources were found in the lockdown period. Health assessment was conducted and characterized by apportioned sources. The highest non-carcinogenic risk (HQ) was seen for Zn, demonstrating the high emissions from the related industrial activities. The concentration level of arsenic (As) exceeded the incremental lifetime carcinogenic risk (ILCR) in the lockdown period. This could be attributed to the traditional firework activities for the celebration of the Chinese New Year within the lockdown period.
Assuntos
Poluentes Atmosféricos , Arsênio , COVID-19 , Metais Pesados , Poluentes Atmosféricos/análise , Efeitos Antropogênicos , China , Cromo , Controle de Doenças Transmissíveis , Poeira/análise , Monitoramento Ambiental , Humanos , Manganês , Material Particulado/análise , Titânio , ZincoRESUMO
OBJECTIVE: To study the effect of dimethyloxalylglycine (DMOG) on angiogenesis in Choke â ¡ zone of rats cross-zone perforator flaps and its mechanism. METHODS: One hundred and twenty-six adult male Sprague Dawley rats were randomly divided into DMOG group, YC-1 group, and control group, with 42 rats in each group. Cross-zone perforator flap model with size of 12 cm×3 cm was made on the back of rats in the three groups. DMOG group was intraperitoneally injected with DMOG (40 mg/kg) at 1 day before operation, 2 hours before operation, and 1, 2, and 3 days after operation; YC-1 group and control group were intraperitoneally injected with YC-1 (10 mg/kg) and the same amount of normal saline at the same time points, respectively. The survival of flap was observed after operation. At 7 days after operation, the survival area of flap in each group was measured and the survival rate of flap was calculated. Flap transmittance test, gelatin-lead oxide angiography, and HE staining were used to observed the angiogenesis in the Choke â ¡ zone of flaps in each group. Immunohistochemical staining and Western blot were used to detect the expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α) in Choke â ¡ zone of flaps in each group. The expressions of VEGF and HIF-1α were also determined by ELISA at 3, 5, and 7 days. RESULTS: At 7 days after operation, there was no obvious necrosis at the distal end of the flap in DMOG group, while necrosis occurred in both the control group and YC-1 group, mainly located at the distal end. The flap survival rate of DMOG group was 90.28%±1.37%, which was significantly higher than that of YC-1 group (84.28%±1.45%) and control group (85.83%±1.60%) ( P<0.05). DMOG group had more angiogenesis in Choke â ¡ zone and the vascular structure was clear and complete. In YC-1 group and control group, the vessels in Choke â ¡ zone was less and the vascular structure was disordered. The number of vessels was (25.56±1.29)/field in the DMOG group, which was significantly higher than that in the YC-1 group [(7.38±0.54)/field] and the control group [(14.48±0.91)/field] ( P<0.05). At 3, 5, and 7 days after operation, HIF-1α and VEGF expressions in Chokeâ ¡zone of DMOG group were significantly higher than those in YC-1 group and control group ( P<0.05). CONCLUSION: DMOG can promote angiogenesis in Choke â ¡ zone, accelerate the early angiogenesis of the flap, improve the microcirculation and blood supply in the potential zone of the flap, reduce the injury of flap ischemia and hypoxia, and increase the survival rate of the flap.
Assuntos
Retalho Perfurante , Aminoácidos Dicarboxílicos , Animais , Sobrevivência de Enxerto , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Retalho Perfurante/irrigação sanguínea , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To investigate the accuracy and safety of pedicle screw placement assisted by orthopedic robot and C-arm fluoroscopy. METHODS: The clinical data of 36 patients with spinal diseases underwent surgical treatment from January 2019 to August 2020 was retrospectively analyzed. Among them, 18 cases were implanted pedicle screws assisted by orthopaedic robot(observation group), including 12 males and 6 females, aged from 16 to 61 years with an average of (38.44±3.60) years;there were 1 case of adolescent scoliosis, 1 case of spinal tuberculosis, 7 cases of lumbar spondylolisthesis, 4 cases of thoracic fracture and 5 cases of lumbar fracture. Another 18 cases were implanted pedicle screws assisted by C-arm fluoroscopy(control group), including 10 males and 8 females, aged from 18 to 58 years with an average of (43.22±2.53) years;there were 1 case of adolescent scoliosis, 6 cases of lumbar spondylolisthesis, 6 cases of thoracic fracture and 5 cases of lumbar fracture. The intraoperative fluoroscopy times, nail placement time and postoperative complications were recorded in two groups. CT scan was performed after operation. The Gertzbein-Robbins standard was used to evaluate the accuracy of pedicle screw placement which was calculated. RESULTS: The number of intraoperative fluoroscopy in observation group was(6.89±0.20) times, which was significantly higher than that in control group(14.00±0.18)times(P<0.05). The placement time of each screw in observation group was(2.56±0.12) min, which was significantly different from that in control group(4.22±0.17) min (P<0.05). One case of incision infection occurred in control group after operation, and recovered after active dressing change. During the follow-up period, no serious complications such as screw loosening and fracture occurred in two groups, and there was no significant difference in complications between two groups(P>0.05). A total of 107 screws were placed in observation group, including 101 screws in class A, 4 in class B, 2 in class C, 0 in class D and 0 in class E, the accuracy rate of pedicle screw placement=[(number of screws in class A+B) / the number of all screws placed in the group] ×100%=98.1%(105/107); and a total of 104 screws were placed in control group, including 90 screws in class A, 4 in class B, 5 in class C, 5 in class D and 0 in class E, the accuracy rate of pedicle screw implantation=[(number of screws in class A+B/the number of all screws placed in the group]×100%=90.3% (94/104); there was significant difference between two groups (P<0.05). CONCLUSION: Orthopaedic robot assisted pedicle screw placement has the advantages of less fluoroscopy times, shorter screw placement time and higher accuracy, which can further improve the surgical safety and has a broad application prospect in the orthopaedic.
Assuntos
Parafusos Pediculares , Procedimentos Cirúrgicos Robóticos , Robótica , Escoliose , Fusão Vertebral , Cirurgia Assistida por Computador , Adolescente , Adulto , Feminino , Fluoroscopia/métodos , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Fusão Vertebral/métodos , Adulto JovemRESUMO
The secondary formation and diffusion processes of aerosol are extraordinarily complex and significantly impact the environment and human health. Therefore, exploring the process of aerosol formation and diffusion based on independent new tracer has always been a concern. The 7Be and 10Be, which are generated only by the action of cosmic rays, are chemically stable and adsorbed on aerosol for transmission, so they have the potential characteristics of aerosol tracers. Here, we obtained the daily resolution atmospheric 7Be, 10Be, and 10Be/7Be without dust interference in Xi'an autumn and winter (heavy pollution period in a typical polluted area) by accelerator mass spectrometry. It is found that during the rapid formation of secondary aerosols (SA) under the stable 10Be/7Be ratio, which indicates the stable atmospheric vertical structure, the concentration of 7Be and 10Be is significantly negatively correlated (R2 > 0.9) with the aerosol concentration. Therefore, SA relative content in aerosols can be estimated by the dilution amount of 7Be and 10Be to reveal the secondary-formation process of aerosol (33% average contribution to aerosols during the winter heavy air pollution period). Furthermore, we also revealed the physical removal process of aerosols based on 7Be, 10Be, and 10Be/7Be, including precipitation removal and diffusion of vertical atmospheric movement caused by stratospheric air intrusion. In summary, meteoric cosmogenic 7Be and 10Be will provide a new way to study the secondary chemical formation and physical removal of aerosols.