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Dongping Lake is one of the most important regulation and storage lakes along the eastern route of the South-to-North Water Diversion Project in China, the water quality condition of which directly influences the safety of water diverting, because it serves as a Yangtze River water redistribution control point. However, the changes in algae, and in environmental factors affecting their community structures, before and after the water diversion project are rarely reported. In this study, the temporal variations of phytoplankton abundance were examined based on monthly samples collected at three stations from May 2010 to April 2022. The total abundance of algae greatly decreased after the water diversion project was implemented, with a relatively stable biodiversity and evenness before and after the water translocation. Multiple statistical methods were used together with the water quality indices (WQIs) and the nutrient status index (TSIM) to evaluate overall water condition and analyse relationships among environmental factors. The WQIs demonstrated a general "Good" water quality with a seasonal differentiation, and that water conditions during water transfer periods were better than during non-water transfer periods, which may be ascribed to the improved hydraulic conditions and purified water environment during water transfer periods. Redundancy analysis showed that water temperature, ammonia nitrogen, water transparency, and total phosphorus were the most important environmental factors, with relatively decreased contribution rates towards phytoplankton communities after the water translocation. Importantly, some dominant phytoplankton genera of Chlorophyta, Bacillariophyceae, and Cyanophyceae were similarly affected by water transparency, and nitrogen and phosphorus nutrients in summer after the water translocation. These research findings helped us gain a comprehensive understanding of the changing patterns of water quality and microalgae and their relationships before and after the water diversion project, providing a guidance for future lake management in regulating hydraulic conditions and improving water quality of Dongping Lake.
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Lagos , Fitoplâncton , Lagos/química , Monitoramento Ambiental , China , Fósforo/análise , Nitrogênio/análiseRESUMO
There remains no consensus on the effects of changes in the environment factors under the action of water diversions on phytoplankton communities. Herein the changing rules applying to phytoplankton communities subject to water diversion were unveiled based on long-term (2011-2021) time-series observations on Luoma Lake, located on the eastern route of the South-to-North Water Diversion Project. We found that nitrogen decreased and then increased, while phosphorus increased after operation of the water transfer project. Algal density and diversity were not affected by water diversion, while the duration of high algal density was shorter after water diversion. Phytoplankton composition had dramatic differences before and after water transfer. The phytoplankton communities exhibited greater fragility when they first experienced a human-mediated disturbance, and then they gradually adapted to more interferences and acquired stronger stability. We furthermore found the niche of Cyanobacteria narrowed while that of Euglenozoa widened under the pressure of water diversion. In addition to WT and DO, the main environmental factor before water diversion was NH4-N, whereas the effect of NO3-N and TN on phytoplankton communities increased after water diversion. These findings fill the knowledge gap as to the consequence of water diversion on water environments and phytoplankton communities.
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Cianobactérias , Fitoplâncton , Humanos , Lagos , Água , Nitrogênio/análise , Fósforo/análise , China , Monitoramento AmbientalRESUMO
BACKGROUND: Patients with cancer are a high-risk population in the COVID-19 pandemic. We aimed to describe clinical characteristics and outcomes of patients with cancer and COVID-19, and examined risk factors for mortality in this population. METHODS: We did a retrospective, multicentre, cohort study of 205 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and with a pathological diagnosis of a malignant tumour in nine hospitals within Hubei, China, from Jan 13 to March 18, 2020. All patients were either discharged from hospitals or had died by April 20, 2020. Clinical characteristics, laboratory data, and cancer histories were compared between survivors and non-survivors by use of χ2 test. Risk factors for mortality were identified by univariable and multivariable logistic regression models. FINDINGS: Between Jan 13 and Mar 18, 2020, 205 patients with cancer and laboratory-confirmed SARS-CoV-2 infection were enrolled (median age 63 years [IQR 56-70; range 14-96]; 109 [53%] women). 183 (89%) had solid tumours and 22 (11%) had haematological malignancies. The median duration of follow-up was 68 days (IQR 59-78). The most common solid tumour types were breast (40 [20%] patients), colorectal (28 [14%]), and lung cancer (24 [12%]). 54 (30%) of 182 patients received antitumour therapies within 4 weeks before symptom onset. 30 (15%) of 205 patients were transferred to an intensive care unit and 40 (20%) died during hospital admission. Patients with haematological malignancies had poorer prognoses than did those with solid tumours: nine (41%) of 22 patients with haematological malignancies died versus 31 (17%) of 183 patients with solid tumours (hazard ratio for death 3·28 [95% CI 1·56-6·91]; log rank p=0·0009). Multivariable regression analysis showed that receiving chemotherapy within 4 weeks before symptom onset (odds ratio [OR] 3·51 [95% CI 1·16-10·59]; p=0·026) and male sex (OR 3·86 [95% CI 1·57-9·50]; p=0·0033) were risk factors for death during admission to hospital. INTERPRETATION: Patients with cancer and COVID-19 who were admitted to hospital had a high case-fatality rate. Unfavourable prognostic factors, including receiving chemotherapy within 4 weeks before symptom onset and male sex, might help clinicians to identify patients at high risk of fatal outcomes. FUNDING: National Natural Science Foundation of China.
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Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Neoplasias/mortalidade , Neoplasias/patologia , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Pandemias , Pneumonia Viral/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
The present study was carried out in Luoma Lake, a shallow lake in temperate eastern China. Based on a two-year study, the dynamics of phytoplankton functional groups and influencing factors were analyzed. A total of 178 taxa were identified and sorted into 20 codons, according to the phytoplankton functional group classification. In order to find the environmental factors driving phytoplankton variations, fifteen groups were analyzed in detail using redundancy analysis. Groups P (Fragilaria crotonensis), X2 (Chlamydomonas globosa, C. microsphaera and Chroomonas acuta), and MP (Navicula rotaeana) were dominant during low temperature periods, whereas groups X2, S1 (Pseudanabaena limnetica), and W1 (Euglena sp.) were dominant during high temperature periods. Water temperature, total phosphorus, and ammonium were the significant driving factors explaining phytoplankton succession. Furthermore, total phosphorus and ammonium could be broadly used in risk management for potential algal blooms in Luoma Lake.
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Ecossistema , Monitoramento Ambiental , Lagos , Fitoplâncton/classificação , Eutrofização , Fitoplâncton/fisiologia , Estações do Ano , Fatores de TempoRESUMO
Hongze Lake, located in the east route of the South-to-North Water Diversion Project (SNWDP), is a potential drinking water source for the residents along this water diversion project. Based on a monthly sampling at 11 stations in three regions of Hongze Lake, the spatiotemporal distribution pattern of cyanobacteria community was comprehensively investigated from March 2011 to February 2013. A total of 23 cyanobacterial species which belong to 16 genera were identified, and Microcystis was the most predominant cyanobacterial genus mainly composed of Microcystis wesenbergii in Hongze Lake. The cyanobacterial abundance ranged from 0 to 2.6 × 10(7) cells/L, and the average cyanobacteria abundance of Northern region was significantly higher than those of Western region and Eastern region in the 2-year study. The total cyanobacteria abundance and the Microcystis abundance both took on a similar seasonal regularity in the three regions. The results of correlation analysis indicated that Microcystis abundance was correlated with water temperature, chemical oxygen demand (COD)Mn, nitrate (NO3-N), and total nitrogen (TN)/total phosphorus (TP) mass ratio, among which water temperature had the highest correlation coefficient. In summer, cyanobacteria blooms may take place under suitable environmental conditions at some special areas in Hongze Lake, especially where the concurrence of slow water exchange and steady wind direction exists.
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Cianobactérias/crescimento & desenvolvimento , Lagos/microbiologia , Microbiologia da Água , China , Monitoramento Ambiental , Lagos/química , Microcystis/crescimento & desenvolvimento , Nitrogênio/análise , Fósforo/análise , Estações do Ano , Análise Espaço-Temporal , Temperatura , Poluentes Químicos da Água/análiseRESUMO
Neutrophil extracellular traps (NETs), which consist of chromatin DNA studded with granule proteins, are released by neutrophils in response to both infectious and sterile inflammation. Beyond the canonical role in defense against pathogens, the extrusion of NETs also contributes to the initiation, metastasis, and therapeutic response of malignant diseases. Recently, NETs have been implicated in the development and therapeutic responses of various types of tumors. Although extensive work regarding inflammation in tumors has been reported, a comprehensive summary of how these web-like extracellular structures initiate and propagate tumor progression under the specific microenvironment is lacking. In this review, we demonstrate the initiators and related signaling pathways that trigger NETs formation in cancers. Additionally, this review will outline the current molecular mechanisms and regulatory networks of NETs during dormant cancer cells awakening, circulating tumor cells (CTCs) extravasation, and metastatic recurrence of cancer. This is followed by a perspective on the current and potential clinical potential of NETs as therapeutic targets in the treatment of both local and metastatic disease, including the improvement of the efficacy of existing therapies.
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OBJECTIVES: Neoadjuvant chemoimmunotherapy has shown promising results for resectable, locoregionally advanced (LA) head and neck squamous cell carcinoma (L/A HNSCC). We published the first phase II trial of neoadjuvant camrelizumab combined with chemotherapy in resectable, L/A HNSCC, demonstrating it was safe and feasible with favorable pathological complete response (pCR). Here, we report the final analysis results for neoadjuvant chemoimmunotherapy in L/A HNSCC (minimum 2.0 years of follow-up). MATERIALS AND METHODS: Three cycles of chemoimmunotherapy were administered before surgery to patients with L/A HNSCC. Two-year disease-free survival (DFS), overall survival (OS) and quality of life (QOL) were reported. RESULTS: The overall two-year DFS and OS rates were 90 % and 100 %, respectively. With a median follow-up of 33.7 months, 9 of 10 (90 %) patients with pCR were alive and disease free. Patients with TNM stage (II/III) or < 20 % of residual viable tumor trended toward improved DFS; hazard ratio (HR), 0.44 [95 % confidence interval (CI), 0.04-5.28] and HR, 0.26 (95 % CI, 0.03-2.36), respectively. All QLQ-C30 functioning and symptom scales other than nausea and vomiting were resolved at 2 years after the completion of radiotherapy. CONCLUSION: Neoadjuvant camrelizumab in combination with chemotherapy provided encouraging clinical outcomes for patients with L/A HNSCC. Further studies with longer follow-up and larger samples are warranted. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1900025303. Registered Aug 22, 2019. https://www.chictr.org.cn/showproj.html?proj=41380.
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Neoplasias de Cabeça e Pescoço , Imunoterapia , Terapia Neoadjuvante , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Terapia Neoadjuvante/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Idoso , Imunoterapia/métodos , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Phytoplankton and water quality changes in highly urbanized lakes affect the surrounding water safety. However, due to the complexity and variability of natural changes and human disturbances, it is difficult for multi-year research with yearly sampling frequency to cover accurate changes of phytoplankton and water environment or provide constructive suggestions for managers. Based on monthly monitoring data spanning 2011-2020 in a highly urbanized subtropical lake (Hongze Lake, China), Mann-Kendall test, ANOVA analysis and variation partitioning analysis were used to assess the changes of phytoplankton and water environment, and detect dynamic responses of phytoplankton to environmental changes. Rising water temperature during winter and spring, the decrease in nitrate, and the increase in water flow and turbidity were the main environmental characteristics from 2011 to 2020. The average and maximum abundance of Chlorophyta, Bacillariophyta, and Cryptophyta significantly declined, while changes in Cyanobacteria were characterized by an increase of N2-fixing filamentous cyanobacteria and a decrease of non-filamentous cyanobacteria. The rising water temperature during spring may promote the early growth of N2-fixing filamentous cyanobacteria. The decrease in nitrate mainly resulted in the decrease of Chlorophyta and non-filamentous cyanobacteria, and the increase of N2-fixing filamentous cyanobacteria during summer and autumn. The increase of turbidity and water flow inhibited the growth of Chlorophyta, Bacillariophyta, Cryptophyta, and non-filamentous cyanobacteria, but created favourable conditions for the growth of N2-fixing filamentous cyanobacteria. In summer and autumn, managers should focus on the proliferation of N2-fixing filamentous cyanobacteria when precipitation increase, nitrogen nutrients decrease, and non-filamentous cyanobacteria risk under opposite conditions. These findings greatly improved our understanding of the dynamic response of phytoplankton communities to natural changes and anthropogenic disturbances in the urbanized subtropical lakes, and can be used to develop lake management strategies.
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Clorófitas , Cianobactérias , Diatomáceas , Humanos , Fitoplâncton , Lagos/microbiologia , Nitratos , Monitoramento Ambiental/métodos , China , Estações do Ano , Fósforo/análiseRESUMO
Radioresistance is the major factor of glioblastoma multiforme (GBM) treatment failure and relapse. Hypoxia and autophagy are linked to radioresistance and poor prognosis in solid tumors, but mechanisms remain unknown. Thus, we hypothesize that hypoxia may activate autophagy through two critical factors, HIF1A and Beclin-1, resulting in radioresistance of GBM in vitro and in vivo. In this study, we first demonstrated that HIF1A was overexpressed in GBM tissues and predicted a poor prognosis via bioinformatics. Secondly, we determined that hypoxia induced high expression of HIF1A and upregulated levels of Beclin-1 and autophagy, while HIF1A knockdown by shRNA reduced the expression of Beclin-1. Then we revealed the crosstalk and mechanisms of HIF1A-associated-Beclin-1 in three aspects: (a) transcriptional regulation, (b) protein interaction, and (c) HIF1A/BNIP3/Beclin-1 signaling pathway. Furthermore, we confirmed that silencing HIF1A enhanced the radiosensitivity of GBM in vitro and in vivo. Additionally, Beclin-1 suppression by 3-MA could reverse radioresistance induced by HIF1A under hypoxia. In conclusion, we demonstrated that hypoxia triggered autophagy via HIF1A-associated Beclin-1, resulting in radioresistance in GBM. HIF1A knockdown improved GBM radiosensitivity, and silencing Beclin-1 could reverse HIF1A-induced radioresistance under hypoxic conditions. These findings may help us comprehend the molecular underpinnings of hypoxia-induced autophagy and provide a novel perspective and prospective treatment for GBM radiosensitization.
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To investigate the distribution characteristics of the cyanobacteria community and the driving factors in impounded lakes and reservoirs in Shandong on the east route of the South-to-North Water Diversion Project, monthly samples of phytoplankton and the aquatic environment from Nansi Lake, Dongping Lake, Datun Reservoir, Donghu Reservoir, and Shuangwangcheng Reservoir were collected from May to November during 2010 to 2019. A total of 44 planktonic cyanobacteria taxa were identified with 23 filamentous cyanobacteria taxa. Pseudanabaena limnetica, Cylindrospermopsis raciborskii, Microcystis aeruginosa, and Microcystis wesenbergii were the dominant harmful cyanobacteria species, with a high detection frequency and abundance in all lakes and reservoirs. By analyzing the distribution characteristics of the cyanobacteria community in impounded lakes and reservoirs, we found that filamentous cyanobacteria had growth advantages in the water with large hydraulic disturbances, which should be the key points of cyanobacteria prevention and control in the future. Pearson correlation analysis and generalized linear fitting curve results showed that total nitrogen, total phosphorus, water temperature, and water depth played a key role in affecting the growth of P. limnetica, C. raciborskii, M. aeruginosa, and M. wesenbergii. The nitrogen and phosphorus nutrients could promote the growth of harmful cyanobacteria. Due to the good temperature adaptability, P. limnetica could still become the dominant species in early summer and late autumn, and C. raciborskii, M. aeruginosa, and M. wesenbergii had growth advantages when the water temperature was higher than 25â. In addition, shallow water was more conducive to the growth of C. raciborskii. It was suggested that based on strengthening of the control of nitrogen and phosphorus nutrient input in lakes and reservoirs, the key monitoring of P. limnetica in lakes should be conducted in early summer and late autumn, and the growth of C. raciborskii in shallow water areas should be paid close attention in the high temperature period to ensure the safety of water quality.
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Cianobactérias , Lagos , Lagos/microbiologia , Monitoramento Ambiental , Fitoplâncton , Fósforo/análise , Nitrogênio/análiseRESUMO
OBJECTIVE: The combination of stereotactic body radiation therapy (SBRT) and immune checkpoint inhibitors (ICIs) is actively being explored in advanced non-small-cell lung cancer (NSCLC) patients. However, little is known about the optimal fractionation and radiotherapy target lesions in this scenario. This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs. METHODS: The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec. 2015 to Sep. 2021. Patients were grouped according to radiation sites. Progression-free survival (PFS) and overall survival (OS) were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank (Mantel-Cox) test. RESULTS: A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study. Radiation sites included lung lesions (lung group, n=43), bone metastases (bone group, n=24), and brain metastases (brain group, n=57). Compared with the brain group, the mean PFS (mPFS) in the lung group was significantly prolonged by 13.3 months (8.5 months vs. 21.8 months, HR=0.51, 95%CI: 0.28-0.92, P=0.0195), and that in the bone group prolonged by 9.5 months with a 43% reduction in the risk of disease progression (8.5 months vs. 18.0 months, HR=0.57, 95%CI: 0.29-1.13, P=0.1095). The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group. The mean OS (mOS) in the lung and bone groups was longer than that of the brain group, and the risk of death decreased by up to 60% in the lung and bone groups as compared with that of the brain group. When SBRT was concurrently given with ICIs, the mPFS in the lung and brain groups were significantly longer than that of the bone group (29.6 months vs. 16.5 months vs. 12.1 months). When SBRT with 8-12 Gy per fraction was combined with ICIs, the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups (25.4 months vs. 15.2 months vs. 12.0 months). Among patients receiving SBRT on lung lesions and brain metastases, the mPFS in the concurrent group was longer than that of the SBRTâICIs group (29.6 months vs. 11.4 months, P=0.0003 and 12.1 months vs. 8.9 months, P=0.2559). Among patients receiving SBRT with <8 Gy and 8-12 Gy per fraction, the mPFS in the concurrent group was also longer than that of the SBRTâICIs group (20.1 months vs. 5.3 months, P=0.0033 and 24.0 months vs. 13.4 months, P=0.1311). The disease control rates of the lung, bone, and brain groups were 90.7%, 83.3%, and 70.1%, respectively. CONCLUSION: The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients. This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens. Dose fractionation regimens of 8-12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Inibidores de Checkpoint Imunológico , Estudos Retrospectivos , Radiocirurgia/métodosRESUMO
Breast cancer (BC) is the most common cancer in females and BC brain metastasis (BCBM) is considered as the second most frequent brain metastasis. Although the advanced treatment has significantly prolonged the survival in BC patients, the prognosis of BCBM is still poor. The management of BCBM remains challenging. Systemic treatments are important to maintain control of central nervous system disease and improve patients' survival. BCBM medical treatment is a rapidly advancing area of research. With the emergence of new targeted drugs, more options are provided for the treatment of BM. This review features currently available BCBM treatment strategies and outlines novel drugs and ongoing clinical trials that may be available in the future. These treatment strategies are discovered to be more efficacious and potent, and present a paradigm shift in the management of BCBMs.
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The intensity of cyanobacterial blooms that predominate in the world's lakes and reservoirs is variable, which may lead to differing effects on the freshwater ecosystem. Planktonic eukaryotes play key roles in the structure and function of freshwater ecosystems; however, little is known about the influence of cyanobacterial blooms on eukaryotic plankton communities and their function. Herein, the dynamics of eukaryotic plankton communities in Hongze Lake, which is the fourth largest freshwater lake in China, with a range of bloom levels occurred, from low to high, were studied to reveal the effect of cyanobacterial blooms' spatial heterogeneity on planktonic eukaryotes. Results showed that the diversity, richness, and evenness of eukaryotic plankton community were not affected by low level of bloom; however, they were decreased obviously by high level of bloom. Metazoa, Ochrophyta, Chloroplastida, Cryptomonadales, and Ciliophora were the main planktonic eukaryotes in this lake. Metazoa relative abundance declined 25.1% and relative abundance of eukaryotic phytoplankton (mainly Ochrophyta, Chloroplastida, and Cryptomonadales) and Ciliophora increased 17.4% and 2.0%, respectively, during the period with low level of bloom; conversely, the site with the high bloom level manifested the opposite changes. The linkage density of planktonic eukaryotic network was 0.188 and 0.138 with low and high level of bloom, respectively, indicating the stability of planktonic eukaryotes was lower when a high level of bloom occurred compared to that of a low bloom level. Our findings indicate that cyanobacterial blooms should be controlled at low level to avoid their obvious negative impact on microeukaryotes in lakes or reservoirs.
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Cianobactérias , Plâncton , Ecossistema , Eucariotos , Eutrofização , Lagos/microbiologiaRESUMO
Intracellular formation of therapeutic agents has become one of the effective ways for cancer-specific treatment. Herein, a tumor acidity-activatable photothermal/Fenton nanoagent (denoted as CoPy) was constructed based on oxidized zeolitic imidazolate framework-67 (oxZIF-67) nanosheet and pyrrole (Py) monomer for synergistic therapy. The CoPy showed negligible toxicity to normal cell models RAW264.7 and 3T3 cell lines, and could be degraded by ascorbic acid in normal physiological conditions. However, once uptaken by 4T1 cells, the acidic pH led to the release of Co3+, which served as a strong oxidant to induce the polymerization of Py to form polypyrrole (PPy) for site-specific photothermal therapy (PTT). Most appealingly, the PPy could chelate the generated Co2+ in the polymerization process to initiate the Fenton-like reaction, which was more capable to produce highly toxic hydroxyl radical (â¢OH) for chemodynamic therapy (CDT) compared to the free Co2+ ones. In vitro and in vivo experiments demonstrated that all functionalities on CoPy worked collaboratively, and 78% of tumors were inhibited through cooperative PTT/CDT. Such a novel therapeutic nanoagent with tumor selectivity opens new opportunities for combinational treatment paradigms.
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Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Humanos , Radical Hidroxila , Neoplasias/tratamento farmacológico , Polímeros , Pirróis , Nanomedicina TeranósticaRESUMO
Breast cancer is the most common malignant disease in female patients worldwide and can spread to almost every place in the human body, most frequently metastasizing to lymph nodes, bones, lungs, liver and brain. The liver is a common metastatic location for solid cancers as a whole, and it is also the third most common metastatic site for breast cancer. Breast cancer liver metastasis (BCLM) is a complex process. Although the hepatic microenvironment and liver sinusoidal structure are crucial factors for the initial arrest of breast cancer and progression within the liver, the biological basis of BCLM remains to be elucidated. Importantly, further understanding of the interaction between breast cancer cells and hepatic microenvironment in the liver metastasis of breast cancer will suggest ways for the development of effective therapy and prevention strategies for BCLM. In this review, we provide an overview of the recent advances in the understanding of the molecular mechanisms of the hepatic microenvironment in BCLM formation and discuss current systemic therapies for treating patients with BCLM as well as potential therapeutic development based on the liver microenvironment-associated signaling proteins governing BCLM.
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PURPOSE: This study aimed to assess the antitumor activity and safety of neoadjuvant chemotherapy combined with PD-1 inhibitor camrelizumab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: In this single-center, single-arm, phase 2 trial, patients with resectable stage III-IVB HNSCC received chemotherapy [albumin-bound paclitaxel 260 mg/m2 (or docetaxel 75 mg/m2) plus cisplatin 75 mg/m2] and camrelizumab 200 mg on day 1 of each 21-day cycle for three cycles, followed by surgery, and adjuvant radiotherapy. Co-primary end points were pathological complete response (pCR) rate and safety. RESULTS: Thirty patients were enrolled and completed the neoadjuvant therapy, with an objective response rate (ORR) of 96.7% (29/30). Twenty-seven patients underwent surgery without delay, with an R0 resection rate of 92.6% (25/27). The clinical to pathological downstaging rate was 100% (27/27). The pCR rate was 37.0% [95% confidence interval (CI), 19.4%-57.6%], and the major pathological response (MPR) rate was 74.1% (95% CI, 53.7%-88.9%). The median follow-up duration was 16.1 months (range, 8.3-28.5), and the disease-free survival rate at 12 months was 95.8% (95% CI, 73.9%-99.4%). Grade 3 neoadjuvant therapy-related adverse events included rash (1; 3.3%), pruritis (1; 3.3%), and thrombocytopenia (1; 3.3%), and no grade 4 or 5 treatment-related events occurred. The most common surgical complication was delayed wound healing (5; 18.5%). CONCLUSIONS: Neoadjuvant chemotherapy plus camrelizumab for locally advanced HNSCC showed high ORR, pCR, and MPR rates, with an acceptable safety profile. These data support further evaluation of neoadjuvant chemoimmunotherapy for the treatment of locally advanced HNSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Cisplatino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Terapia Neoadjuvante/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológicoRESUMO
BACKGROUND: The COVID-19 pandemic is a significant worldwide health crisis. Breast cancer patients with COVID-19 are fragile and require particular clinical care. This study aimed to identify the clinical characteristics of breast cancer patients with COVID-19 and the risks associated with anti-cancer treatment. METHODS: The medical records of breast cancer patients with laboratory-confirmed COVID-19 were collected among 9559 COVID-19 patients from seven designated hospitals from 13th January to 18th March 2020 in Hubei, China. Univariate and multivariate analyses were performed to assess risk factors for COVID-19 severity. RESULTS: Of the 45 breast cancer patients with COVID-19, 33 (73.3%) developed non-severe COVID-19, while 12 (26.7%) developed severe COVID-19, of which 3 (6.7%) patients died. The median age was 62 years, and 3 (6.7%) patients had stage IV breast cancer. Univariate analysis showed that age over 75 and the Eastern Cooperative Oncology Group (ECOG) score were associated with COVID-19 disease severity (P < 0.05). Multivariate analysis showed that patients who received chemotherapy within 7 days had a significantly higher risk for severe COVID-19 (logistic regression model: RR = 13.886, 95% CI 1.014-190.243, P = 0.049; Cox proportional hazards model: HR = 13.909, 95% CI 1.086-178.150, P = 0.043), with more pronounced neutropenia and higher LDH, CRP and procalcitonin levels than other patients (P < 0.05). CONCLUSIONS: In our breast cancer cohort, the severity of COVID-19 could be associated with baseline factors such as age over 75 and ECOG scores. Chemotherapy within 7 days before symptom onset could be a risk factor for severe COVID-19, reflected by neutropenia and elevated LDH, CRP and procalcitonin levels.
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , COVID-19/diagnóstico , Neutropenia/etiologia , SARS-CoV-2/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Proteína C-Reativa , China/epidemiologia , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Pessoa de Meia-Idade , Neutropenia/epidemiologia , Pandemias , Pró-Calcitonina/sangue , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: The prevalence of gene translocation in some mesenchymal tumors can be used as highly specific molecular diagnostic markers in clinic and pathology. EWSR1 is a partner gene in a large, diverse range of mesenchymal tumors. CASE DESCRIPTION: This paper describes the case of a 31-year-old man who was diagnosed with a primary intracranial mesenchymal tumor with EWSR1-CREM gene fusion and eventually returned to a normal live with no signs of tumor recurrence or metastasis after treatment, including surgery therapy, radiotherapy, and 6 cycles of vincristine-doxorubicin-cyclophosphamide chemotherapy, even though the classification and grade of the tumor are still controversial. CONCLUSIONS: This case is a novel entity of intracranial mesenchymal neoplasm with EWSR1-CREM gene fusion which was confirmed by histopathology, molecular pathology, and next-generation sequencing (NGS). The literature review shows only 5 cases of intracranial tumor harboring EWSR1-CREM gene fusion with similar features. With the further application of molecular pathology and NGS in clinical practice, there will be more intracranial mesenchymal tumor cases with EWSR1-CREM gene fusion found in the future, which may lead to further understanding of the diagnosis and clinical features of this neoplasm.
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Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Modulador de Elemento de Resposta do AMP Cíclico/genética , Fusão Gênica/genética , Proteína EWS de Ligação a RNA/genética , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Humanos , Masculino , Células-Tronco Mesenquimais/patologiaRESUMO
Diatoms play an important role as ecological indicators, and some species of diatoms can easily cause water blooms, thereby decreasing the production capacity of water treatment plants and endangering drinking water safety. Mastering the diatom community dynamics is crucial for water supply. In this study, diatom composition, spatial distribution and succession were investigated in Datun Reservoir, Donghu Reservoir and Shuangwangcheng Reservoir, which are important drinking water sources in Shandong province, China. Results showed that the three reservoirs could be classified as being between mesotrophic and moderately eutrophic. The diatom community in each of the three reservoirs exhibited no obvious seasonal succession. The diatom communities in the three reservoirs were relatively simple in composition, with Synedra and Cyclotella being the most dominant groups all year round. Synedra had a negative relationship with NO2-N. Cyclotella had a positive association with NO3-N, but was negatively associated with NH4-N and CODMn in the three reservoirs. Through the analysis of diatom and environmental factors, the three reservoirs have the potential of hosting diatom blooms in summer, when the higher temperature combines with reduced water flow.
Assuntos
Diatomáceas/crescimento & desenvolvimento , Monitoramento Ambiental , Abastecimento de Água/estatística & dados numéricos , China , Fósforo/análise , Estações do AnoRESUMO
To systematically explore the genes mediating functional crosstalk between metazoan biological processes, we apply comparative genetic interaction (GI) mapping in Saccharomyces cerevisiae and Caenorhabditis elegans to generate an inter-bioprocess network consisting of 178 C. elegans GIs. The GI network spans six annotated biological processes including aging, intracellular transport, microtubule-based processes, cytokinesis, lipid metabolic processes, and anatomical structure development. By proposing a strategy called "reciprocal functional test" for interacting gene pairs, we discover a group of genes that mediate crosstalk between distinct biological processes. In particular, we identify the ribosomal S6 Kinase/RSKS-1, previously characterized as an mTOR (mechanistic target of rapamycin) effector, as a regulator of DAF-2 endosomal recycling transport, which traces a functional correlation between endocytic recycling and aging processes. Together, our results provide an alternative and effective strategy for identifying genes and pathways that mediate crosstalk between bioprocesses with little prior knowledge.