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1.
Water Res ; 257: 121670, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38723347

RESUMO

In this study, the performance of a novel up-flow electrocatalytic hydrolytic acidification reactor (UEHAR) and anoxic/oxic (ANO2/O2) combined system (S2) was compared with that of a traditional anaerobic/anoxic/oxic (ANA/ANO1/O1) system (S1) for treating coking wastewater at different hydraulic retention time (HRT). The effluent non-compliance rates of chemical oxygen demand (COD) of S2 were 45 %, 35 %, 25 % and 55 % lower than S1 with HRT of 94, 76, 65 and 54 h. The removal efficiency of benzene, toluene, ethylbenzene and xylene (BTEX) in S2 was 10.6 ± 2.4 % higher than that in S1. The effluent concentration of volatile phenolic compounds (VPs) in S2 was lower than 0.3 mg/L. The dehydrogenase activity (DHA) and adenosine triphosphate (ATP) of O2 were enhanced by 67.2 ± 26.3 % and 40.6 ± 14.2 % compared with O1, respectively. Moreover, COD was used to reflect the mineralization index of organic matter, and the positive correlation between COD removal rate and microbial activity, VPs, and BTEX was determined. These results indicated that S2 had extraordinary microbial activity, stable pollutant removal ability, and transcendental effluent compliance rate.

2.
Int Immunopharmacol ; 133: 112053, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38615380

RESUMO

Although PD-1 inhibitors have revolutionized the treatment paradigm of non-small cell lung cancer (NSCLC), their efficacy in treating NSCLC has remained unsatisfactory. Targeting cancer-associated fibroblasts (CAFs) is a potential approach for improving the immunotherapy response. Multitarget antiangiogenic tyrosine kinase receptor inhibitors (TKIs) can enhance the efficacy of PD-1 inhibitors in NSCLC patients. However, the effects and mechanisms of antiangiogenic TKIs on CAFs have not been elucidated. In this study, we first compared anlotinib with other antiangiogenic TKIs and confirmed the superior efficacy of anlotinib. Furthermore, we established NSCLC-associated CAF models and found that anlotinib impaired CAF viability and migration capacity and contributed to CAF apoptosis and cell cycle arrest in the G2/M phase. Moreover, anlotinib treatment attenuated the capacity of CAFs to recruit lung cancer cells and macrophages. Experiments in animal models suggested that anlotinib could enhance the efficacy of anti-PD1 therapy in NSCLC and affect CAF proliferation and apoptosis. Anlotinib increased the abundance of tumor-infiltrating CD8 + T cells, and PD-1 inhibitor-induced cytotoxicity to tumor cells was achieved through the transformation of the tumor microenvironment (TME) caused by anlotinib, which may partly explain the synergistic antitumor effect of anlotinib and PD-1 inhibitors. Mechanistically, anlotinib affects CAF apoptosis and cell viability at least in part by inhibiting the AKT pathway. In conclusion, our study suggested that anlotinib could regulate the TME, inhibit the AKT pathway and promote CAF apoptosis, providing new insights into the antitumor effect of anlotinib and improving the efficacy of immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Apoptose , Indóis , Neoplasias Pulmonares , Receptor de Morte Celular Programada 1 , Proteínas Proto-Oncogênicas c-akt , Quinolinas , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Animais , Indóis/farmacologia , Indóis/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Apoptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Camundongos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Camundongos Endogâmicos BALB C , Sinergismo Farmacológico
3.
Patient Prefer Adherence ; 18: 709-720, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524198

RESUMO

Background: Colorectal, and gastric cancers have the second, and fourth mortality rates worldwide, respectively. Endoscopic screening is a crucial diagnostic tool for colorectal, and gastric cancers. Effective interventions can improve adherence to endoscopic screening in high-risk populations, which is important for cancer prevention and mortality reduction. This study aimed to identify interventions that could improve adherence to endoscopic screening for cancer in high-risk populations. Methods: Combination keywords including colorectal cancer, gastric cancer, screening adherence, and interventions were used to search for articles in PubMed, Web of Science, Cochrane Library, and MEDLINE Complete. The review methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SCR). Results: A total of 12 articles were included in this review: 9 randomized controlled trials(RCT) and 3 quasi-experimental studies(QEDs). Among the extracted studies, 11 were about colorectal cancer, and 1 was about gastric cancer. Most studies used lecture-based or Information Technology-based health education interventions. Narrative interventions have proven to be novel and effective approaches for promoting adherence to endoscopic screening. Health education interventions included cancer epidemiology, cancer risk factors, warning symptoms, and screening methods. Conclusion: All interventions involved were effective in increasing individual knowledge of cancer-related endoscopic screening, willingness to undergo screening, and screening behaviors. These findings provide a reference for designing endoscopy-related cancer screening interventions.

4.
Public Health Nurs ; 41(3): 476-486, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468509

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival. OBJECTIVES: The aim of this study was to identify the facilitators and barriers to participation in HCC screening among high-risk populations. METHODS: A comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at-risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta-analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of seven articles met the inclusion criteria. Qualitative (n = 1) and quantitative (n = 6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta-analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk et al. CONCLUSIONS: Many barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high-risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Incidência
5.
World J Gastroenterol ; 30(6): 542-555, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38463023

RESUMO

BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are important prognostic factors for gastric cancer (GC) that indicate an increased risk of metastasis and poor outcomes. Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment decisions. However, prior models using conventional computed tomography (CT) images to predict LVI or PNI separately have had limited accuracy. Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion. We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients. AIM: To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately. METHODS: This study used a retrospective dataset involving 257 GC patients (training cohort, n = 172; validation cohort, n = 85). First, several clinical indicators, including serum tumor markers, CT-TN stages and CT-detected extramural vein invasion (CT-EMVI), were extracted, as were quantitative spectral CT parameters from the delineated tumor regions. Next, a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters. A logistic regression (LR)-based nomogram model was subsequently constructed to predict LVI/PNI status, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: In both the training and validation cohorts, CT T3-4 stage, CT-N positive status, and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant (P < 0.05). LR analysis of the training group showed preoperative CT-T stage, CT-EMVI, single-energy CT values of 70 keV of venous phase (VP-70 keV), and the ratio of standardized iodine concentration of equilibrium phase (EP-NIC) were independent influencing factors. The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824, respectively, which were slightly greater than those of CT-T and CT-EMVI (AUC = 0.793, 0.762). The nomogram combining CT-T stage, CT-EMVI, VP-70 keV and EP-NIC yielded AUCs of 0.918 (0.866-0.954) and 0.874 (0.784-0.936) in the training and validation cohorts, which are significantly higher than using each of single independent factors (P < 0.05). CONCLUSION: The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC, with accuracy boosted by integrating clinical markers.


Assuntos
Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Prognóstico , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X/métodos , Aprendizado de Máquina
6.
Nurs Open ; 11(2): e2085, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38391107

RESUMO

AIM: A specific, valid and reliable measure is much needed to dynamically assess the recovery of symptoms in oesophagectomy patients. This study describes developing and validating the Convalescent Symptom Assessment Scale for oesophagectomy patients (CSAS_EC). DESIGN: An instrument development and cross-sectional validation study was conducted. METHODS: This study consists of two components: instrument development and psychometric tests. In instrument development, the literature review, qualitative interviews, Delphi method expert consultation and face validation were used to develop and refine scale content. In psychometric tests, the clinical test version scale was used to conduct a cross-sectional in the thoracic surgery department from 17 June to 20 November 2022. The Classical Test Theory and Multidimensional Item Response Theory (MIRT) analyses examined psychometric properties. RESULTS: In instrument development, literature review (n = 20), qualitative interviews (n = 21), expert consultation (n = 12) and pre-survey (n = 15) led to the development of the clinical test version scale. In psychometric tests, a total of 331 participants were enrolled. Confirmatory factor analysis and MIRT analysis verified that a model with 28 items in four dimensions was good. The four dimensions were early recovery symptoms, late recovery symptoms, persistent present symptoms and psychosocial symptoms. The Cronbach's α is 0.827. The validity and reliability were demonstrated to be acceptable. CONCLUSIONS: The CSAS_EC scale can be used as a tool to evaluate the recovery status of oesophagectomy patients.


Assuntos
Convalescença , Esofagectomia , Humanos , Estudos Transversais , Esofagectomia/efeitos adversos , Reprodutibilidade dos Testes , Avaliação de Sintomas
7.
Eur J Oncol Nurs ; 68: 102501, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38194901

RESUMO

PURPOSE: The objective of this randomized controlled trial was to examine the effectiveness of promoted resilience intervention to facilitate resilience, self-efficacy, coping mode, and social support for oesophageal cancer patients in rural China. METHODS: A two-arm, parallel design, single-blinded, randomized controlled trial was conducted in a comprehensive tertiary hospital in Anhui from August 2021 to September 2022. A total of 82 oesophageal cancer patients were assigned to two groups via blocked randomization. The intervention group (n = 41) received the Promoted Psychological Resilience Intervention based on survivors' experiences and the control group (n = 41) received routine care. Study data were collected using the sociodemographic information, Connor-Davidson Resilience Scale, Strategies Used by People to Promote Health, Medical Coping Modes Questionnaire, and Perceived Social Support Scale. RESULTS: The groups were well-balanced at baseline. Post-intervention and three months after intervention, the resilience, self-efficacy, acceptance-resignation, and social support were all significantly different in the intervention and control groups (p < 0.05 for each). The main effect of group, time, and the interaction between group and time was statistically significant in the scores of resilience, self-efficacy, acceptance-resignation, and social support, except for the factor of self-determination and friends support (p < 0.05 for each). CONCLUSIONS: This study demonstrated that an intervention program based on the experiences of long-term oesophageal cancer survivors can promote patients' resilience.


Assuntos
Neoplasias Esofágicas , Testes Psicológicos , Resiliência Psicológica , Humanos , Adaptação Psicológica , Promoção da Saúde , China
8.
Org Lett ; 26(4): 971-976, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38265233

RESUMO

Cinnamoyl-containing nonribosomal peptides (CCNPs) constitute a unique family of actinobacterial secondary metabolites that display a broad spectrum of biological activities. Here, we present a genome mining approach targeting cyclase and is isomerase to discover new CCNPs, which led to the identification of 207 putative CCNP gene clusters from public bacterial genome databases. After strain prioritization, a novel class of CCNP-type glycopeptides named malacinnamycin was identified. A plausible biosynthetic pathway for malacinnamycin was deduced by bioinformatics analysis.


Assuntos
Biologia Computacional , Peptídeos , Vias Biossintéticas/genética , Genoma Bacteriano , Família Multigênica , Cinamatos/química
9.
Angew Chem Int Ed Engl ; 63(10): e202314046, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38072825

RESUMO

Cyclic peptides with cyclophane linkers are an attractive compound type owing to the fine-tuned rigid three-dimensional structures and unusual biophysical features. Cytochrome P450 enzymes are capable of catalyzing not only the C-C and C-O oxidative coupling reactions found in vancomycin and other nonribosomal peptides (NRPs), but they also exhibit novel catalytic activities to generate cyclic ribosomally synthesized and post-translationally modified peptides (RiPPs) through cyclophane linkage. To discover more P450-modified multicyclic RiPPs, we set out to find cryptic and unknown P450-modified RiPP biosynthetic gene clusters (BGCs) through genome mining. Synergized bioinformatic analysis reveals that P450-modified RiPP BGCs are broadly distributed in bacteria and can be classified into 11 classes. Focusing on two classes of P450-modified RiPP BGCs where precursor peptides contain multiple conserved aromatic amino acid residues, we characterized 11 novel P450-modified multicyclic RiPPs with different cyclophane linkers through heterologous expression. Further mutation of the key ring-forming residues and combinatorial biosynthesis study revealed the order of bond formation and the specificity of P450s. This study reveals the functional diversity of P450 enzymes involved in the cyclophane-containing RiPPs and indicates that P450 enzymes are promising tools for rapidly obtaining structurally diverse cyclic peptide derivatives.


Assuntos
Produtos Biológicos , Ciclofanos , Peptídeos/química , Peptídeos Cíclicos/química , Biologia Computacional/métodos , Sistema Enzimático do Citocromo P-450/metabolismo , Processamento de Proteína Pós-Traducional , Produtos Biológicos/química
10.
Breast Cancer Res Treat ; 203(3): 543-551, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37897648

RESUMO

PURPOSE: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method. RESULTS: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46 years (mean, 48.1 years; range, 10-80 years). The tumor sizes ranged from 0.3 to 6.8 cm, with a mean of 3.5 cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients. CONCLUSION: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve diagnosis and management in this unique subtype of breast cancer.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma , Neoplasias de Mama Triplo Negativas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/patologia , Hibridização in Situ Fluorescente , China , Prognóstico , Neoplasias de Mama Triplo Negativas/patologia
11.
J Am Chem Soc ; 145(50): 27325-27335, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38069901

RESUMO

Cyclization of linear peptides is an effective strategy to convert flexible molecules into rigid compounds, which is of great significance for enhancing the peptide stability and bioactivity. Despite significant advances in the past few decades, Nature and chemists' ability to macrocyclize linear peptides is still quite limited. P450 enzymes have been reported to catalyze macrocyclization of peptides through cross-linkers between aromatic amino acids with only three examples. Herein, we developed an efficient workflow for the identification of P450-modified RiPPs in bacterial genomes, resulting in the discovery of a large number of P450-modified RiPP gene clusters. Combined with subsequent expression and structural characterization of the products, we have identified 11 novel P450-modified RiPPs with different cross-linking patterns from four distinct classes. Our results greatly expand the structural diversity of P450-modified RiPPs and provide new insights and enzymatic tools for the production of cyclic peptides.


Assuntos
Produtos Biológicos , Ribossomos , Ribossomos/metabolismo , Peptídeos/química , Peptídeos Cíclicos/química , Sistema Enzimático do Citocromo P-450/metabolismo , Processamento de Proteína Pós-Traducional , Produtos Biológicos/química
12.
Orthop Surg ; 15(12): 3101-3107, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37817420

RESUMO

OBJECTIVE: The treatment of distal third humeral shaft fracture is difficult. Studies have shown that anterior minimally invasive plate has lower probability of complication and higher healing rate. However there is no applicable anatomical plate at present. This study is to investigate the clinical effect of intramedullary nail combined with anterior minimally invasive plate in the treatment of distal humeral shaft fractures. METHODS: The data of 83 patients with lower humerus shaft fracture treated from September 2015 to January 2020 were analyzed. According to different treatment methods, they were divided into two groups: 40 patients were treated with intramedullary nailing combined with minimally invasive anterior plate fixation (group A), and 43 patients were treated with double plate fixation through posterior approach (group B). General preoperative data, operative time, intraoperative blood loss, total incision length, fracture healing time, shoulder and elbow visual analogue scale (VAS) score, Constant-Murley shoulder function score, Mayo elbow function score, and complications were recorded and compared between the two groups. Two independent sample t-tests was used for follow-up, age, BMI, operation time, intraoperative bleeding, total incision length, fracture healing time, Constant-Murley score and Mayo score, and rank sum test was used for VAS score of shoulder and elbow. RESULTS: There was no significant difference in preoperative general data between the two groups (p > 0.05), indicating comparability. There were no significant differences in operation time, total incision length, fracture healing time, Constant-Murley shoulder function score at the last follow-up, Mayo elbow function score, and shoulder and elbow VAS pain score between 2 groups (p > 0.05). The amount of intraoperative blood loss in observation group was 76.98 ± 16.46, which was significantly less than that in control group, and the difference was statistically significant (p < 0.01). There were no radial nerve injury, musculocutaneous nerve injury, incision infection and fracture nonunion in the observation group. In the control group, four cases of iatrogenic radial nerve injury, three cases of incision infection and three cases of fracture nonunion were found. The complication rate was 23.3% (10/43). There was statistical difference in the incidence of complications between the two groups (p < 0.01). CONCLUSION: A humeral intramedullary nail combined with an anterior minimally invasive plate in the treatment of distal humeral shaft fracture has the advantages of less soft tissue damage, less blood transfusion, high fracture healing rate and low risk of iatrogenic radial nerve injury, which is an effective method for clinical treatment of this type of fracture.


Assuntos
Fixação Intramedular de Fraturas , Fraturas Distais do Úmero , Fraturas do Úmero , Humanos , Fraturas do Úmero/cirurgia , Perda Sanguínea Cirúrgica , Fixação Interna de Fraturas/métodos , Fixação Intramedular de Fraturas/métodos , Placas Ósseas , Úmero , Consolidação da Fratura , Infecção da Ferida Cirúrgica , Doença Iatrogênica , Resultado do Tratamento , Estudos Retrospectivos
13.
J Transl Med ; 21(1): 651, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37737201

RESUMO

BACKGROUND: Pathological neovascularization plays a pivotal role in the onset and progression of tumors and neovascular eye diseases. Despite notable advancements in the development of anti-angiogenic medications that target vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), the occurrence of adverse reactions and drug resistance has somewhat impeded the widespread application of these drugs. Therefore, additional investigations are warranted to explore alternative therapeutic targets. In recent years, owing to the swift advancement of high-throughput sequencing technology, pan-cancer analysis and single-cell sequencing analysis have emerged as pivotal methodologies and focal areas within the domain of omics research, which is of great significance for us to find potential targets related to the regulation of pathological neovascularization. METHODS: Pan-cancer analysis and scRNA-seq data analysis were employed to forecast the association between Actin filament-associated protein 1 like 1 (AFAP1L1) and the development of tumors and endothelial cells. Tumor xenograft model and ocular pathological neovascularization model were constructed as well as Isolectin B4 (IsoB4) staining and immunofluorescence staining were used to assess the effects of AFAP1L1 on the progression of neoplasms and neovascular eye diseases in vivo. Transwell assay, wound scratch assay, tube forming assay, three-dimensional germination assay, and rhodamine-phalloidin staining were used to evaluate the impact of AFAP1L1 on human umbilical vein endothelial cells (HUVECs) function in vitro; Dual luciferase reporting, qRT-PCR and western blot were used to investigate the upstream and downstream mechanisms of pathological neovascularization mediated by AFAP1L1. RESULTS: Our investigation revealed that AFAP1L1 plays a crucial role in promoting the development of various tumors and demonstrates a strong correlation with endothelial cells. Targeted suppression of AFAP1L1 specifically in endothelial cells in vivo proves effective in inhibiting tumor formation and ocular pathological neovascularization. Mechanistically, AFAP1L1 functions as a hypoxia-related regulatory protein that can be activated by HIF-1α. In vitro experiments demonstrated that reducing AFAP1L1 levels can reverse hypoxia-induced excessive angiogenic capacity in HUVECs. The principal mechanism of angiogenesis inhibition entails the regulation of tip cell behavior through the YAP-DLL4-NOTCH axis. CONCLUSION: In conclusion, AFAP1L1, a newly identified hypoxia-related regulatory protein, can be activated by HIF-1α. Inhibiting AFAP1L1 results in the inhibition of angiogenesis by suppressing the germination of endothelial tip cells through the YAP-DLL4-NOTCH axis. This presents a promising therapeutic target to halt the progression of tumors and neovascular eye disease.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Células Endoteliais , Neovascularização Patológica , Humanos , Inibidores da Angiogênese , Proteínas de Ligação ao Cálcio , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular , Animais
14.
J Cancer Surviv ; 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37460857

RESUMO

BACKGROUND: Patients with advanced pancreatic ductal adenocarcinoma (PDAC) need timely medical assistance since the emergence of complications due to the disease and antitumor treatment. Studies have confirmed that instant messaging can improve the quality of life and compliance of cancer patients. However, the prognostic role of instant doctor-patient communication based on instant messaging applications in PDAC has not been studied. METHODS: Patients with PDAC who received first-line chemotherapy at Peking Union Medical College Hospital between January 2015 and October 2022 were reviewed. We categorized patients into two groups according to whether they received WeChat-based instant doctor-patient communication, and the prognosis and toxicity data between the two groups were compared. RESULTS: A total of 431 PDAC patients were enrolled, of whom 163 had long-term instant communication with their doctors based on WeChat, and 268 did not receive WeChat-based instant communication. There was no significant correlation between WeChat-based communication and first-line chemotherapy overall response rate (14.1% vs. 8.6%, p = 0.074), incidence of grade ≥ 3 adverse events (66.9% vs. 65.7%, p = 0.814) or overall survival (14.7 vs. 13.9 months, p = 0.170) in all enrolled patients. However, patients who received WeChat-based instant communication had a higher completion rate of first-line chemotherapy (42.0% vs. 30.7%, p = 0.023). Consistently, in the patients who developed grade ≥ 3 adverse events (n = 231), those who received WeChat-based instant communication had significantly longer overall survival (17.3 vs. 15.3 months, p = 0.018), even after adjustment for biases. CONCLUSIONS: WeChat-based instant doctor-patient communication demonstrated no superiority in improving the efficacy of chemotherapy or preventing chemotherapy toxicity in PDAC patients, but it may contribute to improving the completion rate of chemotherapy and the prognosis in patients who experienced severe adverse events. IMPLICATIONS FOR CANCER SURVIVORS: Instant doctor‒patient communication may help to timely and appropriately deal with adverse events and prolong the survival time of patients with PDAC, supporting the promotion of mobile technology in clinical practice.

15.
Aging Dis ; 14(6): 2177-2192, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37199594

RESUMO

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment, but its clinical benefit is limited in advanced gastric cancer (GC). Cancer-associated fibroblasts (CAFs) have been reported to be associated with ICB resistance, but the underlying mechanism has not been fully elucidated. Our previous single-cell RNA-seq analysis of GC revealed that POSTN+FAP+ extracellular matrix CAFs (eCAFs) communicate with macrophages. Here, we evaluated the correlation between eCAFs and ICB response in TCGA-STAD and real-world cohorts. Immune infiltration analysis and correlation analysis were performed to assess the relationship between eCAFs and macrophages. We first confirmed a negative correlation between the abundance of eCAFs and the overall response rate (ORR) to anti-PD-1 treatment in TCGA-STAD and real-world GC cohorts. Overexpression of POSTN in CAFs enhanced macrophage chemotaxis, while POSTN interference showed the opposite effect in vitro and in vivo. Furthermore, the cell density of POSTN+ CAFs was positively correlated with the infiltration level of CD163+ macrophages in GC patient tissues. The results demonstrated that POSTN secreted by CAFs enhances macrophage chemotaxis by activating the Akt signaling pathway in macrophages. Additionally, we found that POSTN+FAP+ eCAFs may exist in multiple solid tumors and are associated with ICB resistance. eCAFs promote macrophage chemotaxis through the secretion of POSTN, thereby leading to ICB resistance. High expression of POSTN is likely to predict a poor response to ICB. POSTN downregulation may be considered as a candidate therapeutic strategy to improve ICB efficacy.

16.
J Clin Nurs ; 32(13-14): 4116-4127, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36895018

RESUMO

AIM: To design a protocol based on the experiences of long-term survivors to facilitate resilience for oesophageal cancer patients in rural China. BACKGROUND: According to the latest Global Cancer Statistics Report, 604,000 new cases of oesophageal cancer were reported, of which over 60% of the disease burden is distributed in China. The incidence of oesophageal cancer in rural China (15.95/100,000) is twice as high as those in urban areas (7.59/100,000). To be sure, resilience can help patients better adapt to post-cancer life. But universal interventions involving improving the resilience of oesophageal cancer patients have much less been explored, especially for rural patients. METHODS: The two-arm, parallel design, non-blinded, randomised controlled trial will be implemented in 86 adults diagnosed with oesophageal cancer and will be randomly assigned to the control group or the intervention group via the blocked randomisation. The intervention group will undergo an intervention with one-on-one guidance from a nurse while viewing a CD of the experiences of long-term survivors with oesophageal cancer in rural areas. Every 2 weeks, a theme session will be introduced, and the entire intervention will continue for 12 weeks. Psychosocial variables (resilience, self-efficacy, coping mode and family support) will be surveyed at baseline, post-intervention and 3 months after the intervention. The paper complies with the Standard Protocol Items: Recommendations for Intervention Trials 2013 and Consolidated Standards of Reporting Trials guidelines for study protocols adapted for designing and reporting parallel group randomised trials. CONCLUSION: The intervention programme transitions from hospitalisation to discharge, which includes one-on-one interventions by medical personnel and a portable CD describing the experiences of long-term survivors with rural oesophageal cancer. Once the intervention's effectiveness is proven, this protocol will provide psychological support for massive oesophageal cancer patients. RELEVANCE TO CLINICAL PRACTICE: The intervention programme may be used as an auxiliary therapy to promote patients' postoperative psychological rehabilitation. This programme has the advantages of being cost-effective, flexible, accessible, and convenient and can be implemented without the limitation of time, place and clinical medical staff. TRIAL REGISTRATION: The Chinese Clinical Trial Registration number is ChiCTR2100050047. Registered on 16 August 2021.


Assuntos
COVID-19 , Neoplasias Esofágicas , Adulto , Humanos , SARS-CoV-2 , Sobreviventes , Efeitos Psicossociais da Doença , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
J Clin Nurs ; 32(17-18): 5579-5595, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36802111

RESUMO

AIMS AND OBJECTIVE: To systematically review and synthesise existing qualitative research evidence describing the survival experience of patients undergoing oesophagectomy during recovery. BACKGROUND: Patients with oesophageal cancer undergoing surgical treatment have severe physical and psychological burdens during the recovery period. Qualitative studies on the survival experience of patients undergoing oesophagectomy are increasing annually, but there is no integration of qualitative evidence. DESIGN: A systematic review and synthesis of qualitative studies were conducted following the ENTREQ. METHODS: Five English (CINAHL, Embase, PubMed, Web of Science and Cochrane Library) and three Chinese (Wanfang, CNKI and VIP) databases were searched for literature on the survival of patients undergoing oesophagectomy during the recovery period from its establishment in April 2022. The quality of the literature was evaluated by the 'Qualitative Research Quality Evaluation Criteria for the JBI Evidence-Based Health Care Centre in Australia', and the data were synthesised by the thematic synthesis method of Thomas and Harden. RESULTS: A total of 18 studies were included, and four themes were identified: physical and mental dual challenges, impaired social functioning, efforts to return to normal life, lack of knowledge and skills in post-discharge care, and thirst for external support. CONCLUSIONS: Future research should focus on the problem of reduced social interaction during the recovery of patients with oesophageal cancer, formulating individualised exercise intervention programs and establishing a sound social support system. RELEVANCE TO CLINICAL PRACTICE: The results of this study provide evidence-based support for nurses to carry out targeted interventions and reference methods for patients with oesophageal cancer to rebuild their lives. NO PATIENT OR PUBLIC CONTRIBUTION: The report was a systematic review and did not involve a population study.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Humanos , Assistência ao Convalescente , Alta do Paciente , Pesquisa Qualitativa , Neoplasias Esofágicas/cirurgia
18.
Angew Chem Int Ed Engl ; 62(5): e202214026, 2023 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-36458944

RESUMO

Lorneic acid and related natural products are characterized by a trialkyl-substituted benzene ring. The formation of the aromatic core in the middle of the polyketide chain is unusual. We characterized a cytochrome P450 enzyme that can catalyze the hallmark benzene ring formation from an acyclic polyene substrate through genetic and biochemical analysis. Using this P450 as a beacon for genome mining, we obtained 12 homologous type I polyketide synthase (PKS) gene clusters, among which two gene clusters are activated and able to produce trialkyl-substituted aromatic polyketides. Quantum chemical calculations were performed to elucidate the plausible mechanism for P450-catalyzed benzene ring formation. Our work expands our knowledge of the catalytic diversity of cytochrome P450.


Assuntos
Policetídeos , Policetídeos/química , Benzeno , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Sistema Enzimático do Citocromo P-450 , Metabolismo Secundário
19.
Chemosphere ; 312(Pt 1): 137215, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36375608

RESUMO

Polybrominated diphenyl ethers (PBDEs) are efficient brominated flame retardants and are released into various environmental media via usage, recycling and disposal. This study investigated the concentrations and ecological risks of two typical PBDEs, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209), in surface waters across China from 2011 to 2018. The results showed that the concentration of BDE-209 (8.25 ng L-1) was higher than that of BDE-47 (1.02 ng L-1), and the concentrations of BDE-47 and BDE-209 in the lakes (2.56 ng L-1 and 22.19 ng L-1, respectively) were higher than those in the rivers (0.58 ng L-1 and 7.05 ng L-1, respectively). In addition, the concentration of BDE-209 in the wet season (2.61 ng L-1) was lower than that in the dry season (10.83 ng L-1), whereas the concentration of BDE-47 in the wet season (0.24 ng L-1) was a little lower than that in the dry season (0.99 ng L-1). BDE-47 and BDE-209 concentrations showed a gradual decrease in surface waters across China during the eight-year period. Based on the species sensitivity distribution (SSD) models, the 5% hazardous concentration (HC5) and predicted no-effect concentration (PNEC) values were derived using the acute and chronic toxicity data of BDE-47 and BDE-209. Results showed that the PNEC values based on the acute and chronic toxicity data were 2.08 µg L-1 and 0.52 µg L-1 for BDE-47, respectively and 370 µg L-1 and 0.34 µg L-1 for BDE-209, respectively. The risk quotient (RQ) values of BDE-47 in surface waters across China were far smaller than 0.1 (low ecological risk). Similarly, the RQ values of BDE-209 were also smaller than 0.1, except for those at Baiyangdian Lake and Chaohu Lake, where the probability of 0.1 ≤ RQ < 1.0 (medium ecological risk) was approximately 10% based on 10,000 Monte Carlo simulations.


Assuntos
Retardadores de Chama , Éteres Difenil Halogenados , Éteres Difenil Halogenados/análise , Monitoramento Ambiental , Éter , Retardadores de Chama/análise , Medição de Risco , Etil-Éteres , China
20.
Rev. bras. med. esporte ; 29: e2022_0720, 2023. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1423498

RESUMO

ABSTRACT Introduction: Contemporary table tennis teaching lacks attention to global abilities; some studies suggest that functional training can supply the demands of the high level of sport competition. Objective: Study the effect of functional training on teaching table tennis to college students. Methods: A controlled random selection was carried out (n=40), in which the experimental group (n=20) chose a functional training program. In contrast, the control group (n=20) participated in the teaching of traditional table tennis skills. The training frequency was one hour daily, three times a week, lasting six weeks. Table tennis-specific fitness was assessed before and after the experiment. Data were cataloged and statistically analyzed. Results: On the manual skills index, the experimental group's score increased from 63,194 to 79,683 points after the experiment, and the control group's score increased from 64,788 to 68,775 points after the experiment. In the regression index, the experimental group score increased from 63.645 to 78.614, and the control group score increased from 64.152 to 70.574. Conclusion: The functional training mode proposed in this paper can rapidly improve the competitive level of table tennis and improve the competitive performance of its practitioners. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.


RESUMO Introdução: O ensino contemporâneo no tênis de mesa carece de atenção em habilidades globais, alguns estudos sugerem que o treinamento funcional possa suprir as demandas requisitadas pelo alto nível de competição esportiva. Objetivo: Estudar o efeito do treinamento funcional sobre o ensino do tênis de mesa nos estudantes universitários. Métodos: Foi realizada uma seleção randômica controlada (n=40), na qual o grupo experimental (n=20) escolheu um programa de treinamento funcional, enquanto o grupo de controle (n=20) participou do ensino das habilidades tradicionais do tênis de mesa. A frequência do treinamento foi de uma hora diária, três vezes por semana, com duração de seis semanas. A aptidão física específica do tênis de mesa foi avaliada antes e depois do experimento. Os dados foram catalogados e analisados estatisticamente. Resultados: No índice de habilidades manuais, a pontuação do grupo experimental aumentou de 63.194 para 79.683 pontos após o experimento, e a pontuação do grupo de controle aumentou de 64.788 para 68.775 pontos após o experimento. No índice de retrocesso, a pontuação do grupo experimental aumentou de 63.645 para 78.614, e a pontuação do grupo de controle aumentou de 64.152 para 70.574. Conclusão: O modo de treinamento funcional proposto neste artigo pode melhorar rapidamente o nível competitivo do tênis de mesa e melhorar o desempenho competitivo de seus praticantes. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.


RESUMEN Introducción: La enseñanza contemporánea en tenis de mesa carece de atención en habilidades globales, algunos estudios sugieren que el entrenamiento funcional puede suplir las demandas requeridas por el alto nivel de competición deportiva. Objetivo: Estudiar el efecto del entrenamiento funcional en la enseñanza del tenis de mesa en estudiantes universitarios. Métodos: Se realizó una selección aleatoria controlada (n=40), en la que el grupo experimental (n=20) eligió un programa de entrenamiento funcional, mientras que el grupo de control (n=20) participó en la enseñanza de las habilidades tradicionales del tenis de mesa. La frecuencia del entrenamiento fue de una hora diaria, tres veces por semana, con una duración de seis semanas. Se evaluó la forma física específica del tenis de mesa antes y después del experimento. Los datos se catalogaron y analizaron estadísticamente. Resultados: En el índice de habilidades manuales, la puntuación del grupo experimental aumentó de 63,194 a 79,683 puntos después del experimento, y la del grupo de control aumentó de 64,788 a 68,775 puntos después del experimento. En el índice de regresión, la puntuación del grupo experimental aumentó de 63,645 a 78,614, y la del grupo de control, de 64,152 a 70,574. Conclusión: El modo de entrenamiento funcional propuesto en este artículo puede mejorar rápidamente el nivel competitivo del tenis de mesa y mejorar el rendimiento competitivo de sus practicantes. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

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