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2.
Complement Ther Med ; : 103052, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38763206

RESUMO

OBJECTIVE: The purpose of this systematic review was to examine the association between folic acid supplementation during pregnancy and the risk of preeclampsia. METHODS: Relevant studies were included by searching Embase, PubMed, Scope, Web of science, Cochrane Library databases. Studies were reviewed according to prespecified inclusion and exclusion criteria. Study characteristics were summarized, and study quality was assessed. Risk ratios (RR) and 95% confidence intervals (CI) were used as indicators of effect to assess the relationship between folic acid supplementation and risk of preeclampsia. RESULTS: The protocol of this study was prospectively registered with the PROSPERO (registration No. CRD42022380636).A total of nine studies were included, divided into three groups according to the type of study, containing a total of 107 051 and 105 222 women who were supplemented and not supplemented with folic acid during pregnancy. The results showed that folic acid supplementation during pregnancy could not be proven to reduce the risk of preeclampsia. CONCLUSION: The results of the study suggest that folic acid supplementation alone is not associated with a decreased risk of pre-eclampsia,but the inferences are somewhat limited by the low methodological quality of the included literature, and therefore higher quality studies are needed to prove this point.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38692503

RESUMO

OBJECTIVE: To understand the priorities and preferences of people with disabilities (PwDs) and older adults regarding accessible Autonomous Vehicles (AVs) to address existing transportation barriers. DESIGN: Two national surveys, "Voice of the Consumer (VoC)" and "Voice of the Provider (VoP)," were conducted to gather feedback from accessible AV consumers and providers respectively in the United States (US). SETTING: This US based study focused on PwDs and older adults who may face transportation challenges and those who provide or design AV solutions. PARTICIPANTS: The 922 consumers and 45 providers in the surveys encompassed a diverse range of disability types, caregiver roles, and age groups. INTERVENTIONS: Not Applicable MAIN OUTCOME MEASURES: The main outcomes are consumer usage needs and provider preferences for features in accessible autonomous transportation. Patterns in usage needs and feature preferences through two-step clustering algorithm was applied, subsequent to the descriptive analysis of participant demographics and their responses. RESULTS: Participants strongly preferred AV features enhancing personal transportation, especially for rural medical appointments. Most sought comprehensive AV automated features. Wheelchair users emphasized accessible entrances, particularly for lower-income brackets ($25,000 - $49,000). Provider priorities closely aligned with consumer preferences, reinforcing content validity. CONCLUSION: The study highlights the importance of prioritizing wheelchair accessibility in AVs and improving access to medical appointments, especially in rural and low-income communities. Implications include developing inclusive AV services for PwDs and underserved populations. The research establishes a foundation for a more equitable and accessible transportation landscape through AV technology integration.

4.
Heliyon ; 10(7): e28653, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38590905

RESUMO

Background & aims: With a drastic increase in the number of chronic hepatitis B (CHB) patients with coexisting nonalcoholic fatty liver disease (NAFLD), there is an urgent need to evaluate antiviral treatment effects in this special population. Methods: CHB patients with hepatic steatosis (CHB + HS) were prospectively recruited with followed-up of 3 years. HS and liver fibrosis were assessed by transient elastography. HS was defined as controlled attenuation parameter (CAP) ≥248 dB/m, and fibrosis progression was defined with ≥1-stage fibrosis increment. Multivariate and propensity score matching (PSM) analysis were used to evaluate antiviral therapy effects on fibrosis progression. Results: In total 212 recruited CHB + HS patients (median age 36 years, median ALT 59 U/L), 49.1% (104/212) received antiviral therapy and 50.9% (108/212) did not. Among patients with antiviral therapy, rates of serum HBV DNA undetectable, HBeAg and HBsAg loss, and ALT normalization at year 3 were 88.5%, 31.0%, 8.7% and 70.2%, respectively. Patients with mild-moderate HS didn't differ patients with severe HS regarding biochemical and virological responses. Antiviral therapy was independently associated with a lower risk of fibrosis progression among the entire cohort (odds ratio 0.473, 95% CI 0.245-0.911, P = 0.025). This finding was further verified by PSM analysis. When stratified by the severity of HS, the antiviral therapy benefits in reducing fibrosis progression were mainly seen in patients with mild-moderate HS. Conclusions: Among CHB + HS patients, long-term antiviral treatment effectively inhibits HBV replication and reduces fibrosis progression. Our findings have implications for the optimal management of this population.

5.
Front Pharmacol ; 15: 1360972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650625

RESUMO

Ethnopharmacological relevance: As a representative classical prescription, Sijunzi decoction has powerful therapeutic effects on spleen-stomach qi insufficiency. Ulcerative colitis (UC) is a chronic, diffuse, and non-specifically inflammatory disorder, the etiology of which still remains unclear. In the traditional Chinese medicine (TCM) perspective, splenic asthenia is the primary cause of UC. Based on this, Sijunzi decoction has been extensively used in TCM clinical practice to alleviate UC in recent years. However, the pharmacological mechanism of Sijunzi decoction in modern medicine is still not completely clear, which limits its clinical application. Aim of the study: The purpose of this study was to investigate the Sijunzi decoction's curative effect on acute UC mice and probe into its potential pharmacological mechanism. Materials and methods: The UC mouse model was set up by freely ingesting a 3% dextran sulfate sodium (DSS) solution. The relieving role of Sijunzi decoction on UC in mice was analyzed by evaluating the changes in clinical parameters, colon morphology, histopathology, inflammatory factor content, intestinal epithelial barrier protein expression level, and gut microbiota balance state. Finally, multivariate statistical analysis was conducted to elucidate the relationship between inflammatory factors, intestinal epithelial barrier proteins, and gut microbiota. Results: First, the research findings revealed that Sijunzi decoction could visibly ease the clinical manifestation of UC, lower the DAI score, and attenuate colonic damage. Moreover, Sijunzi decoction could also significantly inhibit IL-6, IL-1ß, and TNF-α while increasing occludin and ZO-1 expression levels. Subsequently, further studies showed that Sijunzi decoction could remodel gut microbiota homeostasis. Sijunzi decoction was beneficial in regulating the levels of Alistipes, Akkermansia, Lachnospiraceae_NK4A136_group, and other bacteria. Finally, multivariate statistical analysis demonstrated that key gut microbes were closely associated with inflammatory factors and intestinal epithelial barrier proteins. Conclusion: Sijunzi decoction can significantly prevent and treat UC. Its mechanism is strongly associated with the improvement of inflammation and intestinal epithelial barrier damage by regulating the gut microbiota.

6.
Front Endocrinol (Lausanne) ; 15: 1354577, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577568

RESUMO

Introduction: Osteoporosis, a disease of reduced bone mass and microstructural deterioration leading to fragility fractures, is becoming more prevalent as aging progresses, significantly increasing the socioeconomic burden. In past studies, there has been a growing awareness of the harmful effects of heavy metals on bone, with cadmium being a significant exposure factor. The purpose of this study was to look into the association between adult bone mineral density(BMD) and blood cadmium levels. Methods: Based on information from the 2013-2014, 2017-2018 NHANES, weighted multiple regression, generalized weighted modeling, and smoothed curve fitting were utilized to investigate the association between blood cadmium and femur BMD. Furthermore, subgroup analyses were conducted to investigate any differences in the associations between age, sex, race, chronic kidney disease, and diabetes. Results: In 2,146 participants, blood cadmium levels and total femur [-0.02 (-0.03, -0.01), 0.0027], femoral neck [-0.01 (-0.02, -0.00), 0.0240], femoral trochanter [-0.01 (-0.02, -0.00), 0.0042], and intertrochanteric femoral trochanter [-0.02 (-0.03, -0.00), 0.0101] BMD were negatively correlated. Subgroup analyses showed that this association was more pronounced in women, non-Hispanic white people and other Hispanics, and those with chronic kidney disease and diabetes. Our results pointed to a negative relationship between femoral BMD and blood cadmium. This negative association varied by age, sex, race, diabetes, and chronic kidney disease. In particular, bone mineral density was more significantly negatively affected by blood cadmium levels in groups with diabetes and chronic kidney disease. Conclusion: Our findings demonstrated a significant negative association between blood cadmium levels and bone mineral density in a population of U.S. adults.


Assuntos
Diabetes Mellitus , Insuficiência Renal Crônica , Adulto , Humanos , Feminino , Densidade Óssea , Estudos Transversais , Cádmio , Inquéritos Nutricionais
7.
Zhongguo Fei Ai Za Zhi ; 27(3): 187-192, 2024 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-38590193

RESUMO

BACKGROUND: As a new technique developed in recent years, bronchoscopic intervention therapy has the advantages of minimal invasion, high safety and repeatability. The aim of this study is to investigate the clinical characteristics of bronchopleural fistula (BPF) induced by surgeries for lung malignancies or benign diseases and the effect of bronchoscopic intervention therapy for BPF, so as to provide support for prevention and treatment of BPF. METHODS: Data 64 patients with BPF who were treated by bronchoscopic intervention in Respiratory Disease Center of Dongzhimen Hospital, Beijing University of Chinese Medicine from June 2020 to September 2023 were collected. Patients with fistula diameter ≤5 mm were underwent submucous injection of macrogol, combined with blocking therapy with N-butyl cyanoacrylate, medical bioprotein glue or silicone prosthesis. Patients with fistula diameter >5 mm were implanted with different stents and cardiac occluders. Locations and characteristics of fistulas were summarized, meanwhile, data including Karnofsky performance status (KPS), shortbreath scale (SS), body temperature, pleural drainage volume and white blood cell count before and after operation were observed. RESULTS: For all 64 patients, 96 anatomic lung resections including pneumonectomy, lobectomy and segmentectomy were executed and 74 fistulas occurred in 65 fistula locations. The proportion of fistula in the right lung (63.5%) was significantly higher than that in the left (36.5%). Besides, the right inferior lobar bronchial fistula was the most common (40.5%). After operation, KPS was significantly increased, while SS, body temperature, pleural drainage volume and white blood cell count were significantly decreased compared to the preoperative values (P<0.05). By telephone follow-up or readmission during 1 month to 38 months after treament, median survival time was 21 months. 33 patients (51.6%) showed complete response, 7 patients (10.9%) showed complete clinical response, 18 patients (28.1%) showed partial response, and 6 patients (9.4%) showed no response. As a whole, the total effective rate of bronchoscopic intervention for BPF was 90.6%. CONCLUSIONS: BPF induced by pulmonary surgery can lead to severe symptoms and it is usually life-threating. Bronchoscopic intervention therapy is one of the fast and effective therapeutic methods for BPF.


Assuntos
Fístula Brônquica , Neoplasias Pulmonares , Doenças Pleurais , Humanos , Fístula Brônquica/etiologia , Fístula Brônquica/cirurgia , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/etiologia , Doenças Pleurais/etiologia , Doenças Pleurais/cirurgia , Pleura , Pneumonectomia/efeitos adversos
8.
Front Oncol ; 14: 1357982, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38532934

RESUMO

Due to their unique location, airway tumors have a significant impact on patient quality of life and survival. Current research has focused extensively on malignant airway tumors; however, benign airway tumors, especially rare ones, are less understood due to their low incidence. These tumors are often misdiagnosed and mistreated due to diagnostic challenges. Therefore, there is still a lack of consensus on the treatment of some rare benign airway tumors. Our center summarizes the diagnosis and treatment of four rare cases of benign airway stenosis in recent years, highlighting the bronchoscopic manifestations and therapeutic approaches to improve the understanding of these diseases.

9.
Anal Chim Acta ; 1298: 342408, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38462333

RESUMO

BACKGROUND: In vitro screening strategies based on the inhibition of α-glucosidase (GAA) activity have been widely used for the discovery of potential antidiabetic drugs, but they still face some challenges, such as poor enzyme stability, non-reusability and narrow range of applicability. To overcome these limitations, an in vitro screening method based on GAA@GOx@Cu-MOF reactor was developed in our previous study. However, the method was still not satisfactory enough in terms of construction cost, pH stability, organic solvent resistance and reusability. Thence, there is still a great need for the development of in vitro screening methods with lower cost and wider applicability. RESULTS: A colorimetric sensing strategy based on GAA/(Au-Au/IrO2)@Cu(PABA) cascade catalytic reactor, which constructed through simultaneous encapsulating Au-Au/IrO2 nanozyme with glucose oxidase-mimicking and peroxidase-mimicking activities and GAA in Cu(PABA) carrier with peroxidase-mimicking activity, was innovatively developed for in vitro screening of GAA inhibitors in this work. It was found that the reactor not only exhibited excellent thermal stability, pH stability, organic solvent resistance, room temperature storage stability, and reusability, but also possessed cascade catalytic performance, with approximately 12.36-fold increased catalytic activity compared to the free system (GAA + Au-Au/IrO2). Moreover, the in vitro GAA inhibitors screening method based on this reactor demonstrated considerable anti-interference performance and detection sensitivity, with a detection limit of 4.79 nM for acarbose. Meanwhile, the method owned good reliability and accuracy, and has been successfully applied to the in vitro screening of oleanolic acid derivatives as potential GAA inhibitors. SIGNIFICANCE: This method not only more effectively solved the shortcomings of poor stability, narrow scope of application, and non-reusability of natural enzymes in the classical method compared with our previous work, but also broaden the application scope of Au-Au/IrO2 nanozyme with glucose oxidase and peroxidase mimicking activities, and Cu(PABA) carrier with peroxidase mimicking activity, which was expected to be a new generation candidate method for GAA inhibitor screening.


Assuntos
Ácido 4-Aminobenzoico , Inibidores de Glicosídeo Hidrolases , Inibidores de Glicosídeo Hidrolases/farmacologia , Glucose Oxidase , Reprodutibilidade dos Testes , Colorimetria/métodos , Peroxidases , Solventes , Peróxido de Hidrogênio
10.
Zhongguo Fei Ai Za Zhi ; 27(2): 157-160, 2024 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-38453449

RESUMO

Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly malignant tumor, which includes the following five pathologic types: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. The onset of PSC is occult with non-specific clinical symptoms and signs. The clinical manifestations include irritating cough, bloody sputum, dyspnea, chest pain and so on, which are closely related to the growth and invasion site of the tumor. PSC tends to metastasize early, so most patients are already in local advanced stage or advanced stage with a median survival of 9 months at the time of hospital visit. A patient with primary PSC which led to 90% stenosis in central airway was treated by combined method of vascular and tracheoscopic intervention in our respiratory center. This treatment prolonged the patient's survival time and got a satisfactory effect at 19-month follow-up after surgery. Herein we report the case for clinical reference.
.


Assuntos
Carcinoma , Carcinossarcoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Prognóstico , Carcinoma/patologia , Carcinossarcoma/cirurgia , Carcinossarcoma/patologia , Pulmão/patologia
11.
Ann Med ; 56(1): 2316258, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38364214

RESUMO

INTRODUCTION: Establishing reference ranges for central airway parameters and exploring their influencing factors in Han Chinese non-smoking adults. METHODS: This prospective cross-sectional study was conducted on Han Chinese non-smoking adults who underwent chest CT scans at the Tongzhou Campus of Dongzhimen Hospital Affiliated with the Beijing University of Chinese Medicine between September 2022 and November 2022. The SYNAPSE 3D image analysis software was utilized, enabling the extraction of critical parameters such as central airway length, airway wall thickness (AWT), airway lumen area (ALA), and subcarinal angle (SCA). Pearson's correlation coefficient analysis and multiple linear regression analysis methods were employed to evaluate the relationship between central airway parameters and age, sex, weight, and height. RESULTS: The study encompassed 888 Han Chinese non-smoking adults, comprising 456 females and 432 males. Significant sex differences were noted in central airway length, AWT, and ALA, with measurements in males exceeding those in females (p < 0.01) with no significant difference in SCA. Correlation analyses unveiled relationships between central airway parameters and age, sex, weight, and height. During multiple linear regression analyses, no conclusive evidence emerged to demonstrate the independent or combined explanatory or predictive capacity of the aforementioned variables for central airway length and SCA. Although sex has a significant impact on AWT and ALA, its capability in explanation or prediction remains limited. The conclusions drawn from the primary analysis receive reinforcement from the outcomes of sensitivity analyses. CONCLUSION: Establishing the distribution range of central airway parameters in non-smoking Han Chinese adults. It observed significant sex differences in these parameters, except for the SCA. However, the study found that the predictive or explanatory power of age, sex, weight, and height for central airway parameters was either limited or non-significant.


Assuntos
Sistema Respiratório , Tomografia Computadorizada por Raios X , Adulto , Feminino , Humanos , Masculino , China/epidemiologia , Estudos Transversais , Estudos Prospectivos , População do Leste Asiático , Sistema Respiratório/anatomia & histologia
12.
Curr Res Food Sci ; 8: 100677, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38303998

RESUMO

Our prophase studies have manifested that the sweet triterpenoid glycoside from the leaves of Cyclocarya paliurus (CPST) effectively improved the disorders of glucolipid metabolism in vitro and in patients. The current purpose was to further detect its mechanisms involved. The results demonstrated that CPST could ameliorate high-fat diet (HFD)-induced insulin resistance (IR), which was linked to reducing HFD-induced mice's body weight, serum glucose (GLUO), triglyceride (TG), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C), lowering the area under the oral glucose tolerance curve and insulin tolerance, elevating the percentage of brown adipose, high-density lipoprotein cholesterol (HDL-C), reducing fat droplets of adipocytes in interscapular brown adipose tissue (iBAT) and cross-sectional area of adipocytes. Further studies manifested that CPST obviously downregulated TLR4, MyD88, NLRP3, ASC, caspase-1, cleased-caspase-1, IL-18, IL-1ß, TXNIP, and GSDMD protein expressions and p-NF-кB/NF-кB ratio in iBAT. These aforementioned findings demonstrated that CPST ameliorated HFD induced IR by regulating TLR4/NF-κB/NLRP3 signaling pathway, which in turn enhancing insulin sensitivity and glucose metabolism.

15.
Biosens Bioelectron ; 246: 115872, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38039731

RESUMO

Multicolor-based visual immunosensor is a promising tool for rapid analysis without the use of bulky instruments. Herein, an anti-fenitrothion nanobody-alkaline phosphatase fusion protein (VHHjd8-ALP) was employed to develop a multicolor visual immunosensor (MVIS) and a ratiometric fluorescence MVIS (RFMVIS, respectively). After one-step competitive immunoassay, the VHHjd8-ALP bound to microplate catalyzed phenyl phosphate disodium salt (ArP) into phenol. Under high alkaline condition (pH 12), the phenol reduced KMnO4 to intermediate (K2MnO4) and further to MnO2 in alkaline condition (pH 12), accompanied by a visible color transition of purple-green-yellow, which can be used for semiquantitative visual analysis or qualitative detection by measuring RGB value. RFMVIS was proposed on the basis of MVIS to further improve sensitivity. The CdTe quantum dot and fluorescein were used as signal probes to develop the fluorescent immunosensor. The CdTe dots with red emission (644 nm) was quenched by oxidation of KMnO4, whereas the fluorescein with green emission (520 nm) remained constant, accompanied by a fluorescent color transition of green-yellow-red. By measuring the ratio of the fluorescence intensity (I644/I520), the ratiometric fluorescence immunosensor was developed for qualitative analysis. The two visual immunosensors were sensitive and simple, and they showed good accuracy and practicability in the recovery test, thus are ideal tools for rapid screening.


Assuntos
Técnicas Biossensoriais , Compostos de Cádmio , Pontos Quânticos , Permanganato de Potássio , Fenitrotion , Fosfatos , Compostos de Manganês , Telúrio , Imunoensaio , Óxidos , Fluoresceínas , Fenóis , Corantes Fluorescentes , Limite de Detecção , Espectrometria de Fluorescência
16.
J Formos Med Assoc ; 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38097430

RESUMO

BACKGROUND: The burden of nonalcoholic fatty liver disease (NAFLD) is growing in patients with chronic hepatitis B (CHB). NAFLD is typically associated with obesity, however, it is increasingly being identified in non-obese patients. This study aimed to investigate disease severity and antiviral response in non-obese patients with CHB with NAFLD (CHB + NAFLD). METHODS: A total of 809 patients with CHB + NAFLD were prospectively recruited and followed up for 3 years. NAFLD was diagnosed by transient elastography and defined as controlled attenuation parameter ≥248 dB/m, in the absence of excessive alcohol intake. Obesity status was defined by the Asian body mass index (BMI) cutoff of 25 kg/m2. Metabolic abnormality was defined by the presence of dyslipidemia, hypertension or diabetes. Fibrosis staging was defined according to the EASL-ALEH guidelines, with fibrosis progression defined as ≥1-stage increment. RESULTS: In the total cohort (median age 40 years, 59.0% antiviral-treated), 33.3% were non-obese. Non-obese patients were less metabolically abnormal than obese patients (60.2% vs 72.0%, P = 0.003). After 3-year follow up, the rate of fibrosis progression was comparable between non-obese and obese patients (17.5% vs 21.9% in the total cohort, P = 0.145; 15.7% vs 14.6% in antiviral-treated cohort with persistent viral suppression, P = 0.795). No significant differences in virological and biochemical responses were observed between non-obese and obese patients (P >0.05 for all). CONCLUSIONS: Approximately one third of CHB + NAFLD patients were non-obese. Non-obese patients, while less metabolically abnormal, had a similar risk for fibrosis progression as obese patients. Obesity status did not impact the efficiency of antiviral therapy.

18.
Disabil Rehabil Assist Technol ; : 1-12, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37987718

RESUMO

PURPOSE: This study aimed to explore the requirements for accessible Autonomous Vehicles (AVs) and AV services from a consumer perspective, focusing on people with disabilities (PwDs) and older adults. METHODS: Two national surveys were conducted, capturing current transportation trends and AV priorities. Participants (n = 922) with disabilities and older adults were included in the analysis. RESULTS: Transportation choices exhibited significant divergence based on the underlying causes of disabilities, showcasing distinct inclinations and impediments within each category. AV services, encompassing family conveyance and package delivery, proved integral, but their specific desirability fluctuated in accordance with the nature of disabilities. Notably, medical appointments emerged as the foremost AV utilisation requirement, particularly pronounced among individuals with hearing impairments. Preferences for orchestrating AV rides and the preferred vehicle types displayed disparities linked to the various disability classifications. The employment of mobile applications, websites, and text messages were preferred mediums for arranging rides. Features such as automated route guidance and collision prevention garnered unanimous precedence among AV attributes. Key priorities, spanning wheelchair accessibility, user profiles, and seamless communication with AVs, were universally emphasised across all participant clusters. The study indicated a moderate comfort level with AV deployment, implying the potential for favourable reception within the population of PwDs and older adults. CONCLUSION: The study highlights the significance of considering diverse needs in accessible AV development of vehicle and infrastructure and policies.


The findings inform evidence-based interventions and programmes that prioritise accessibility needs, promoting social inclusion and equitable transportation solutions.Continued research and advocacy are essential for successful autonomous vehicle integration, catering to the needs of all individuals.

19.
Heliyon ; 9(9): e19750, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37810045

RESUMO

Background: Understanding the effects of a delayed time-to-treatment initiation(TTI) for non-small cell lung cancer (NSCLC) is vital. Methods: We analyzed NSCLC data from the Surveillance, Epidemiology, and End Results database, focusing on lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). TTI was studied as both continuous and dichotomous variables. Restricted cubic splines were employed to identify potential nonlinear dependency between the hazard ratio (HR) and TTI. Propensity score matching was used to ensure a balanced patient allocation, and then survival differences between groups were assessed using Kaplan-Meier analysis and competing risk models. We used overall survival (OS) as the primary outcome and cancer-specific cumulative mortality (CSCM) as a complementary indicator. Finally, sensitivity analyses were performed on censored data. Results: A total of 80,020 with NSCLC were analyzed. TTI was assessed as a continuous variable, showing a noticeable increase in the HR for stage I to II NSCLC with TTI >1 month. Conversely, the trend for stage III to IV NSCLC was the opposite. In stage I LUAD, the 'early' group demonstrated a higher OS compared to the 'delayed' group (Log-rank P = 0.002), while there was no significant difference in CSCM (Fine-gray P = 0.321). In stage I LUSC, there was no significant difference in OS(Log-rank P = 0.260), but the 'early' group had a lower CSCM (Fine-gray P = 0.018). For stage II-IV NSCLC, the 'delayed' group did not exhibit a negative impact on OS or CSCM. The sensitivity analysis further supported the results of the main analysis. Conclusion: Prolongation of TTI ≥31 days has a negative impact on OS or CSCM in stage I NSCLC only. Further exploration and validation are needed to determine whether these results can be used as evidence for a 'safe' TTI threshold setting for future NSCLC.

20.
Int Immunopharmacol ; 124(Pt B): 110957, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37734200

RESUMO

BACKGROUND & AIMS: Switching of the macrophage activation phenotype affects the pathogenesis of alcoholic liver diseases, and metabolic reprogramming can provide the energy demand for macrophage phenotypes shift. However, the molecular mechanism by which immune metabolism regulates the activation of proinflammatory macrophages remains unclear. APPROACH: Expression of Fgl2 was examined in patients with alcoholic hepatitis and healthy controls. Mice were fed with a Lieber-DeCarli diet. Livers from mice were used to observe liver injury and macrophage activation. Fgl2 overexpressing THP-1 cell was used to find interacting partners through immunoprecipitation plus mass spectrometry. Naive bone marrow derived macrophages stimulated with LPS and ethanol were used for cell experiments. RESULTS: Expression of Fgl2 was elevated in macrophages of livers from mice with chronic-binge ethanol feeding or patients with alcoholic hepatitis. Fgl2 depletion ameliorated ethanol diet-induced hepatic steatosis and oxidative injury as well as the levels of proinflammatory cytokines. Fgl2-/- mice exhibited suppressed M1 polarization and glycolysis pathway activation. Fgl2 interacted with the M2 isoform of pyruvate kinase (PKM2) in macrophages and facilitated PKM2 nuclear translocation, thus promoting glycolysis in M1 macrophages and the secretion of proinflammatory cytokines. Furthermore, Fgl2 overexpression in THP-1 cells enhances PKM2-dependent glycolysis and inflammation, which could be reversed by activation of enzymatic PKM2 using DASA58. CONCLUSIONS: Taken together, Fgl2 hastens the development of alcoholic liver injury by mediating PKM2 dependent aerobic glycolysis in proinflammatory macrophages. Strategies that inhibiting proinflammatory macrophage activation by silencing Fgl2 might be a potential therapeutic intervention for alcoholic liver injury.


Assuntos
Hepatite Alcoólica , Animais , Humanos , Camundongos , Citocinas/metabolismo , Etanol/toxicidade , Etanol/metabolismo , Fibrinogênio/metabolismo , Glicólise , Hepatite Alcoólica/patologia , Fígado/patologia , Macrófagos , Camundongos Endogâmicos C57BL
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