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1.
Exp Mol Med ; 56(5): 1137-1149, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38689087

RESUMO

Osimertinib, a selective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), effectively targets the EGFR T790M mutant in non-small cell lung cancer (NSCLC). However, the newly identified EGFR C797S mutation confers resistance to osimertinib. In this study, we explored the role of pyruvate dehydrogenase kinase 1 (PDK1) in osimertinib resistance. Patients exhibiting osimertinib resistance initially displayed elevated PDK1 expression. Osimertinib-resistant cell lines with the EGFR C797S mutation were established using A549, NCI-H292, PC-9, and NCI-H1975 NSCLC cells for both in vitro and in vivo investigations. These EGFR C797S mutant cells exhibited heightened phosphorylation of EGFR, leading to the activation of downstream oncogenic pathways. The EGFR C797S mutation appeared to increase PDK1-driven glycolysis through the EGFR/AKT/HIF-1α axis. Combining osimertinib with the PDK1 inhibitor leelamine helped successfully overcome osimertinib resistance in allograft models. CRISPR-mediated PDK1 knockout effectively inhibited tumor formation in xenograft models. Our study established a clear link between the EGFR C797S mutation and elevated PDK1 expression, opening new avenues for the discovery of targeted therapies and improving our understanding of the roles of EGFR mutations in cancer progression.


Assuntos
Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Neoplasias Pulmonares , Mutação , Piruvato Desidrogenase Quinase de Transferência de Acetil , Humanos , Acrilamidas/farmacologia , Acrilamidas/uso terapêutico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Animais , Linhagem Celular Tumoral , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Feminino , Masculino , Indóis , Pirimidinas
2.
Nat Commun ; 15(1): 2936, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580644

RESUMO

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.


Assuntos
Doenças Autoimunes , Colangite , Cirrose Hepática Biliar , Camundongos , Animais , Cirrose Hepática Biliar/terapia , Imunoterapia Adotiva , Receptor de Morte Celular Programada 1 , Linfócitos T CD8-Positivos , Colangite/terapia , Doenças Autoimunes/genética
3.
J Cardiothorac Surg ; 19(1): 155, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532497

RESUMO

BACKGROUND: To demonstrate the effectiveness and feasibility of robotic portal resection (RPR) for mediastinal tumour using a prospectively collected database. METHODS: Data from 73 consecutive patients with mediastinal tumours who underwent RPRs were prospectively collected from August 2018 to April 2023. All patients underwent chest and abdominal enhanced computed tomography (CT) and preoperative multidisciplinary team (MDT) discussion. The patients were stratified into two groups based on tumour size: Group A (tumour size < 4 cm) and Group B (tumour size ≥ 4 cm). General clinical characteristics, surgical procedures, and short outcomes were promptly recorded. RESULTS: All of the cases were scheduled for RPRs. One patient (1/73, 1.4%) was switched to a small utility incision approach because of extensive pleural adhesion. Two patients (2.8%) converted to sternotomy, however, no perioperative deaths occurred. Most of the tumours were located in the anterior mediastinum (51/73, 69.9%). Thymoma (27/73, 37.0%) and thymic cyst (16/73, 21.9%) were the most common diagnoses. The median diameter of tumours was 3.2 cm (IQR, 2.4-4.5 cm). The median total operative time was 61.0 min (IQR, 50.0-90.0 min). The median intraoperative blood loss was 20 mL (IQR, 5.0-30.0 ml), and only one patient (1.4%) experienced an intraoperative complication. The median length of hospital stay was 3 days (IQR, 2-4 days). Compared with Group A, the median total operative time and console time of Group B were significantly longer (P = 0.006 and P = 0.003, respectively). The volume of drainage on the first postoperative day was greater in group B than in group A (P = 0.013). CONCLUSION: RPR is a safe and effective technique for mediastinal tumour treatment, which can expand the application of minimally invasive surgery for the removal of complicated mediastinal tumours.


Assuntos
Neoplasias do Mediastino , Procedimentos Cirúrgicos Robóticos , Robótica , Timoma , Neoplasias do Timo , Humanos , Neoplasias do Mediastino/cirurgia , Robótica/métodos , Neoplasias do Timo/cirurgia , Timoma/cirurgia , Resultado do Tratamento , Estudos Retrospectivos
4.
Talanta ; 273: 125938, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38503125

RESUMO

The expression levels of microRNA (miRNA) vary significantly in correlation with the occurrence and progression of cancer, making them valuable biomarkers for cancer diagnosis. However, their quantitative detection faces challenges due to the high sequence homology, low abundance and small size. In this work, we established a strand displacement amplification (SDA) approach based on miRNA-triggered structural "Lock" nucleic acid ("Lock" DNA), coupled with the CRISPR/Cas12a system, for detecting miRNA-21 in breast cancer cells. The "Lock" DNA freed the CRISPR-derived RNA (crRNA) from the dependence on the target sequence and greatly facilitated the extended detection of different miRNAs. Moreover, the CRISPR/Cas12a system provided excellent amplification ability and specificity. The designed biosensor achieved high sensitivity detection of miRNA-21 with a limit of detection (LOD) of 28.8 aM. In particular, the biosensor could distinguish breast cancer cells from other cancer cells through intracellular imaging. With its straightforward sequence design and ease of use, the Lock-Cas12a biosensor offers significant advantages for cell imaging and early clinical diagnosis.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Neoplasias , Ácidos Nucleicos , MicroRNAs/genética , Sistemas CRISPR-Cas , Diagnóstico por Imagem , Limite de Detecção
5.
World J Gastroenterol ; 30(4): 418-420, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38313234

RESUMO

The present letter to the editor is related to the review with the title "Past, present, and future of long-term treatment for hepatitis B virus." Chronic hepatitis B (CHB) represents an important and pressing public health concern. Timely identification and effective antiviral therapy hold the potential to reduce liver-related mortality attributable to chronic infection with hepatitis B virus (HBV) substantially. However, the current global treatment rates for CHB remain conspicuously low, with the excessively stringent treatment criteria advocated by national CHB guidelines being a contributing factor to these low rates. Nevertheless, recent strides in comprehending this malady and the emergence of novel antiviral agents prompt the imperative re-evaluation of treatment standards to extend the sphere of potential beneficiaries. An impending need arises for a novel paradigm for the classification of patients with CHB, the expansion of antiviral treatment eligibility for HBV-infected individuals, and even the streamlining of the diagnostic process for CHB to amplify cost-effectiveness and augment survival prospects.


Assuntos
Hepatite B Crônica , Humanos , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Vírus da Hepatite B/genética , DNA Viral , Antígenos E da Hepatite B
6.
Anal Chem ; 95(48): 17708-17715, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-38000080

RESUMO

MicroRNAs (miRNAs), a class of small molecules with important regulatory functions, have been widely used in the field of biosensing as biomarkers for the early diagnosis of various diseases. Therefore, it is crucial to develop an miRNA detection platform with high sensitivity and specificity. Here, we have designed a CRISPR/Cas13-based enzymatic cyclic amplification system and regarded the magnetic upconversion nanoparticles (MUCNPs) as a biosensor of outputting the detection signal for the highly sensitive and high-fidelity detection of miRNAs. MUCNPs were composed of UCNPs (fluorescence donors) and Fe3O4@AuNPs (fluorescence acceptors) through double-stranded DNA hybrid coupling. The target miRNA acted as an activator, which could activate the trans-cleavage activity of Cas13a to the well-designed Trigger containing two uracil ribonucleotides (rU) in its loop and trigger a strand displacement reaction to generate a large amount of single-stranded DNA, resulting in the release of the UCNPs from MUCNPs. Benefiting from the high fidelity and high selectivity of CRISPR/Cas13a, the great effect of triggered enzymatic cycle amplification, and the high-intensity luminescent signal of MUCNPs, this method possessed miRNA detection capability with high sensitivity and specificity even in the complex environment with 10% fetal bovine serum (FBS) and a serum sample. Meanwhile, the detection limit could be as low as 83.2 fM. In addition, this method effectively reduced the effect of photobleaching and maintained high stability, which was expected to achieve efficient and sensitive miRNA detection.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , MicroRNAs , MicroRNAs/genética , Ouro , DNA , DNA de Cadeia Simples , Técnicas Biossensoriais/métodos , Limite de Detecção
7.
Zhen Ci Yan Jiu ; 48(7): 625-34, 2023 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-37518955

RESUMO

OBJECTIVE: To observe the effect of acupoint catgut embedding (CE) on Nod-like receptor protein 3 (NLRP3)/Caspase-1 signaling pathway in "deficiency-stasis" syndrome type ulcerative colitis (UC) rats, so as to explore its mechanisms underlying improvement of UC. METHODS: A total of 58 male SD rats were randomly divided into control group (10 rats) and model group (48 rats). The "deficiency-stasis" type UC model was established by gavage of adenine and folium sennae solution for 4 weeks, followed by clycter of mixture solution of 5% trinitro-benzene-sulfonic acid and 50% ethanol. A total of 44 UC rats were randomized into model, salicylazosulfapyridine (SASP), non-acupoint CE, and acupoint CE groups (11 rats in each group). The catgut embedment was applied to bilateral "Zusanli"(ST36), "Shenshu"(BL23), "Pishu"(BL20), "Dachangshu"(BL25), "Geshu" (BL17) and "Tianshu"(ST25), or non-acupoints (the fat muscles of the buttocks), separately, once every two weeks, 3 times altogether. Rats of the SASP group received gavage of SASP solution, and those of the other groups received gavage of same amount of normal saline, once daily for 42 days. The rat's general conditions and the colon length were recorded, the disease activity index (DAI, 0 to 4 points) and colonic mucosal damage index (CMDI, 0 to 5 points) were calculated. Histopathological changes of the colonic mucosa tissue were observed after HE staining, and the tissue damage index (TDI, 0 to 6 points) was given. The levels of serum NLRP3, interleukin (IL)-1ß and IL-18 were measured by ELISA, and the expression levels of NLRP3, Caspase-1, apoptosis-associated speck-like protein (ASC), IL-1ß and IL-18 mRNAs were measured by fluorescence quantitative PCR. The expression levels of NLRP3 and Caspase-1 proteins in the colon tissues were measured by Western blot, and the immunoactivity of colonic ASC was detected by immunohistochemistry. RESULTS: Compared with the control group, the rats' body mass and colonic length were significantly decreased (P<0.01), and DAI score, CMDI score, TDI score, contents of serum NLRP3, IL-1ß and IL-18, expression levels of colonic NLRP3, ASC, Caspase-1, IL-1ß and IL-18 mRNAs, and NLRP3 and Caspase -1 proteins as well as colonic ASC immunoactivity were significantly up-regulated in the model group (P<0.01). Compared with the model group, both SASP and acupoint CE groups had a significant increase in body mass and colonic length (P<0.01), and a marked decrease in DAI score, CMDI score, TDI score, contents of serum NLRP3, IL-1ß and IL-18, expression levels of NLRP3, ASC, Caspase-1, IL-1ß and IL-18 mRNAs and NLRP3 and Caspase-1 proteins and ASC immunoactivity (P<0.01). The above indexes were improved in the acupoint CE group in relevant to those of the non-acupoint CE group (P<0.01). HE staining of colonic mucosal tissue showed obvious ulcerative surface, destroyed recess, disordered arrangement of glands, mucosal edema and congestion, infiltration of a large number of inflammatory cells in the model group, which was obviously milder in both SASP and acupoint CE groups. CONCLUSION: Acupoint embedding can alleviate colonic injury and inhibit inflammatory reaction in rats with "deficiency-stasis" type UC by down-regulating colonic NLRP3/Caspase-1 signaling.


Assuntos
Colite Ulcerativa , Ratos , Masculino , Animais , Colite Ulcerativa/genética , Colite Ulcerativa/terapia , Ratos Sprague-Dawley , Interleucina-18/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Categute , Caspases , Transdução de Sinais , Sulfassalazina , Caspase 1/genética
8.
Talanta ; 265: 124849, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37421793

RESUMO

It is of great significance to develop a highly sensitive and intuitive virus detection tool. A portable platform is constructed for quantitative detection of viral DNA based on the principle of fluorescence resonance energy transfer (FRET) between upconversion nanoparticles (UCNPs) and graphene oxide nanosheets (GOs) in this work. To implement a high sensitivity and low detection limit, GOs are modified by magnetic nanoparticles to prepare magnetic graphene oxide nanosheets (MGOs). Among them, the application of MGOs can not only eliminate the background interference, but also amplify the fluorescence intensity to a certain extent. Whereafter, a simple carrier chip based on photonic crystals (PCs) is introduced to realize a visual solid-phase detection, which also amplifies the luminescence intensity of the detection system. Finally, under the application of the 3D printed accessory and smartphone program of red-green-blue (RGB) evaluation, the portable detection can be completed simply and accurately. In a word, this work proposes a portable DNA biosensor with the triple functions of quantification, visualization and real-time detection can be used as a high-quality viral detection strategy and clinical diagnosis method.


Assuntos
Técnicas Biossensoriais , Nanopartículas de Magnetita , Nanopartículas , Smartphone , Limite de Detecção , Nanopartículas/química , DNA Viral/genética , Técnicas Biossensoriais/métodos
9.
Clin Lung Cancer ; 24(6): e226-e235, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37263866

RESUMO

BACKGROUND: We aimed to investigate the impact of the number of harvested lymph nodes (LNs) on the overall survival (OS) and disease-free survival (DFS) of patients with clinical node-negative (cN0) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 2247 patients with cN0 NSCLC between 2001 and 2014 were included. Scatter plots of hazard ratios from Cox proportional hazards models against the number of harvested LNs were created, and curves were fitted using a LOWESS smoother. Chow test was used to determine the cut-off points for the optimal number of harvested LNs. Long-term survival was compared between groups divided by the cut-off points. RESULTS: The increasing numbers of harvested LNs and N2 level LNs were independent factors favoring OS and DFS. Seventeen LNs and 10 N2 level LNs were determined as the optimal cut-off points. The patients with ≥17 harvested LNs had a better OS (P = .001) and DFS (P = .002), while the patients with ≥10 harvested N2 level LNs also had a better OS (P < .001) and DFS (P = .001). The increasing numbers of harvested LNs and N2 level LNs were independent prognostic factors associated with prolonged OS and DFS only in patients with clinical T2 (cT2) NSCLC. CONCLUSIONS: The increasing numbers of harvested LNs and N2 level LNs were associated with better OS and DFS in cN0 NSCLC patients that were suitable for lobectomies. At least 17 LNs and 10 N2 level LNs were required to be harvested, especially in cT2 patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Linfonodos/patologia , Excisão de Linfonodo , Prognóstico , Estudos Retrospectivos
10.
Thorac Cancer ; 14(16): 1512-1519, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37128686

RESUMO

BACKGROUND: To explore whether robotic lobectomy (RL) is superior to video-assisted lobectomy (VAL) in terms of short-term outcomes in patients with pulmonary neoplasms. METHODS: From January 30, 2019 to February 28, 2022, a series of consecutive minimally invasive lobectomies were performed for patients with pulmonary neoplasms. Perioperative outcomes such as operation time, blood loss, dissected lymph nodes (LNs), surgical complications, postoperative pain control, length of postoperative stay in hospital, and total cost of hospitalization were compared. RESULTS: A total of 336 cases including 173 RLs and 163 VALs were enrolled. Baseline characteristics were comparable between groups. RLs were associated with shorter operation time (median [interquadrant range, IQR], 107 min [90-130] vs. 120 min [100-149], p < 0.001), less blood loss (median [IQR], 50 mL [30-60] vs. 50 mL [50-80], p = 0.02), and lower blood transfusion rate (3.5% vs. 9.8%, p = 0.02) compared with VALs. More LNs were harvested by the robotic approach (median [IQR], 29 [20-41] vs. 22 [15-45], p = 0.04). The incidences of conversion, major postoperative complications, extra analgesic usage, and postoperative length of stay were all comparable between the RL and VAL groups. As predicted, the total cost of hospitalization was greater in the RL group (median [IQR], $16728.35 [15682.16-17872.15] vs. $10713.47 [9662.13-11742.15], p < 0.001). CONCLUSION: RL improved surgical efficacy with shortened operative time, less blood loss, and more thorough LN dissection compared with VAL, compromised by higher cost.


Assuntos
Neoplasias Pulmonares , Procedimentos Cirúrgicos Robóticos , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Pneumonectomia/efeitos adversos , Neoplasias Pulmonares/patologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Tempo de Internação , Cirurgia Torácica Vídeoassistida/efeitos adversos
11.
Chin J Integr Med ; 29(8): 750-760, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37148482

RESUMO

Ulcerative colitis (UC) is a chronic, non-specific intestinal disease that not only affects the quality of life of patients and their families but also increases the risk of colorectal cancer. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is an important component of inflammatory response system, and its activation induces an inflammatory cascade response that is involved in the development and progression of UC by releasing inflammatory cytokines, damaging intestinal epithelial cells, and disrupting the intestinal mucosal barrier. Chinese medicine (CM) plays a vital role in the prevention and treatment of UC and is able to regulate NLRP3 inflammasome. Many experimental studies on the regulation of NLRP3 inflammasome mediated by CM have been carried out, demonstrating that CM formulae with main effects of clearing heat, detoxifying toxicity, drying dampness, and activating blood circulation. Flavonoids and phenylpropanoids can effectively regulate NLRP3 inflammasome. Other active components of CM can interfere with the process of NLRP3 inflammasome assembly and activation, leading to a reduction in inflammation and UC symptoms. However, the reports are relatively scattered and lack systematic reviews. This paper reviews the latest findings regarding the NLRP3 inflammasome activation-related pathways associated with UC and the potential of CM in treating UC through modulation of NLRP3 inflammasome. The purpose of this review is to explore the possible pathological mechanisms of UC and suggest new directions for development of therapeutic tools.


Assuntos
Colite Ulcerativa , Colite , Humanos , Inflamassomos/metabolismo , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Medicina Tradicional Chinesa , Qualidade de Vida
12.
JCI Insight ; 8(8)2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-36881472

RESUMO

Primary Sjögren's syndrome (pSS) is a systemic autoimmune inflammatory disease mainly defined by T cell-dominated destruction of exocrine glands. Currently, CD8+ T cells are thought to be involved in the pathogenesis of pSS. However, the single-cell immune profiling of pSS and molecular signatures of pathogenic CD8+ T cells have not been well elucidated. Our multiomics investigation showed that both T cells and B cells, especially CD8+ T cells, were undergoing significant clonal expansion in pSS patients. TCR clonality analysis revealed that peripheral blood granzyme K+ (GZMK+) CXCR6+CD8+ T cells had higher a proportion of clones shared with CD69+CD103-CD8+ tissue-resident memory T (Trm) cells in labial glands in pSS. CD69+CD103-CD8+ Trm cells featured by high expression of GZMK were more active and cytotoxic in pSS compared with their CD103+ counterparts. Peripheral blood GZMK+CXCR6+CD8+ T cells with higher CD122 expression were increased and harbored a gene signature similar to Trm cells in pSS. Consistently, IL-15 was significantly elevated in pSS plasma and showed the capacity to promote differentiation of CD8+ T cells into GZMK+CXCR6+CD8+ T cells in a STAT5-dependent manner. In summary, we depicted the immune profile of pSS and further conducted comprehensive bioinformatics analysis and in vitro experimental investigations to characterize the pathogenic role and differentiation trajectory of CD8+ Trm cells in pSS.


Assuntos
Síndrome de Sjogren , Humanos , Linfócitos T CD8-Positivos , Diferenciação Celular , Granzimas/metabolismo , Glândulas Salivares Menores , Análise de Célula Única
13.
Ann Surg Oncol ; 30(5): 2757-2764, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36774436

RESUMO

BACKGROUND: Our study aimed to compare the short-term outcomes between robot-assisted segmentectomy (RAS) and video-assisted segmentectomy (VAS) for small pulmonary nodules. METHODS: The study included of 299 segmentectomies (132 RAS and 167 VAS procedures) for small pulmonary nodules between June 2018 and November 2021. The patients were divided into two groups: the RAS group and the VAS group. Propensity score-matching (PSM) analysis was performed to minimize bias. A logistic regression model was performed to identify the independent risk factors associated with complications. RESULTS: Before PSM, the following clinical variables were not balanced: age (P = 0.004), tumor size (P < 0.001), forced expiratory volume for 1 s (FEV1), and FEV1 percentage (P < 0.001). The patients with RAS had a shorter operative time (P = 0.014), less blood loss, a shorter postoperative hospital stay, less use of strong opioids, less drainage on postoperative day 1, and less postoperative total drainage, but more cost (all P < 0.001). Conversion to open surgery was performed for two patients in the VAS group but none in the RAS group. After PSM, 53 pairs were successfully matched. The data again suggested that the patients with RAS had less blood loss, a shorter postoperative hospital stay, and less use of strong opioids, but more cost (all P < 0.001). The operation time also was shorter in the RAS group, with a borderline statistically significant P value (0.053). CONCLUSIONS: In our study, RAS had better short-term outcomes than VAS, indicating a safer and more efficient technique than VAS.


Assuntos
Nódulos Pulmonares Múltiplos , Robótica , Humanos , Pneumonectomia/métodos , Pontuação de Propensão , Mastectomia Segmentar , Cirurgia Torácica Vídeoassistida/efeitos adversos , Estudos Retrospectivos
16.
J Robot Surg ; 17(4): 1477-1484, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36787021

RESUMO

Although robotic segmentectomy has been applied for the treatment of small pulmonary lesions for many years, studies on the learning curve of robotic segmentectomy are quite limited. Thus, we aim to investigate the learning curve of robotic portal segmentectomy with 4 arms (RPS-4) using prospectively collected data in patients with small pulmonary lesions. One hundred consecutive patients with small pulmonary lesions who underwent RPS-4 between June 2018 and April 2021 were included in the study. Da Vinci Si/Xi systems were used to perform RPS-4. The mean operative time, console time, and docking time for the entire cohort were 119.2 ± 41.6, 85.0 ± 39.6, and 6.6 ± 2.8 min, respectively. The learning curve of RPS-4 can be divided into three different phases: 1-37 cases (learning phase), 38-78 cases (plateau phase), and > 78 cases (mastery phase). Moreover, 64 cases were required to ensure acceptable surgical outcomes. The total operative time (P < 0.001), console time (P < 0.001), blood loss (P < 0.001), and chest tube duration (P = 0.014) were reduced as experience increased. In conclusion, the learning curve of RPS-4 could be divided into three phases. 37 cases were required to pass the learning phase, and 78 cases were needed to truly master this technique.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Pneumonectomia , Curva de Aprendizado , Estudos Retrospectivos , Duração da Cirurgia
17.
Chinese Pharmacological Bulletin ; (12): 1463-1469, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013727

RESUMO

Aim To investigate the regulatory effects of 3-bromopyruvate (3-BrPA) on apoptosis and autophagy of fibroblast-like synoviocytes (FLS) in rats based on AMPK/mTOR signaling pathway and the underlying mechanism. Methods FLS of rats in vitro were cultured and induced by tumor necrosis factor-α (TNF-α) to construct a model of rheumatoid arthritis (R A). MTT assay was used to explore the optimal concentration of TNF-α and 3 -BrPA for induction and treatment of FLS. The effects of 3-BrPA on the migration and invasion of FLS were detected by Wound healing assay and Transwell assay. The apoptosis of FLS was tested by flow cytometry and mitochondrial membrane potential assay kit (JC-1). Moreover, FLS autophagic flux was detected by mCherry-EGFP-LC3B-overexpressed plasmids, and the expression of apoptosis/autophagy-related proteins as well as AMPK/mTOR pathway-related proteins were detected by Western blot. Results 3-BrPA (15 μmol • L) significantly inhibited the proliferation, migration, and invasion of FLS stimulated by TNF-a (25 μg • L

18.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-982305

RESUMO

Ulcerative colitis (UC) is a chronic, non-specific intestinal disease that not only affects the quality of life of patients and their families but also increases the risk of colorectal cancer. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is an important component of inflammatory response system, and its activation induces an inflammatory cascade response that is involved in the development and progression of UC by releasing inflammatory cytokines, damaging intestinal epithelial cells, and disrupting the intestinal mucosal barrier. Chinese medicine (CM) plays a vital role in the prevention and treatment of UC and is able to regulate NLRP3 inflammasome. Many experimental studies on the regulation of NLRP3 inflammasome mediated by CM have been carried out, demonstrating that CM formulae with main effects of clearing heat, detoxifying toxicity, drying dampness, and activating blood circulation. Flavonoids and phenylpropanoids can effectively regulate NLRP3 inflammasome. Other active components of CM can interfere with the process of NLRP3 inflammasome assembly and activation, leading to a reduction in inflammation and UC symptoms. However, the reports are relatively scattered and lack systematic reviews. This paper reviews the latest findings regarding the NLRP3 inflammasome activation-related pathways associated with UC and the potential of CM in treating UC through modulation of NLRP3 inflammasome. The purpose of this review is to explore the possible pathological mechanisms of UC and suggest new directions for development of therapeutic tools.


Assuntos
Humanos , Inflamassomos/metabolismo , Colite Ulcerativa/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Medicina Tradicional Chinesa , Qualidade de Vida , Colite
19.
World J Gastrointest Surg ; 14(5): 514-520, 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35734619

RESUMO

BACKGROUND: Castleman disease is an uncommon nonclonal lymphoproliferative disorder, which frequently mimics both benign and malignant abnormalities in several regions. Depending on the number of lymph nodes or regions involved, Castleman disease (CD) varies in diagnosis, treatment and prognosis. It rarely occurs in the pancreas alone without any distinct clinical feature and tends to be confused with pancreatic paraganglioma (PGL), neuroendocrine tumors (NETs), and primary tumors, thus impeding proper diagnosis and treatment. CASE SUMMARY: A 28-year-old woman presented with a lesion on the neck of the pancreas, detected by ultrasound during a health examination. Physical examination and laboratory findings were normal. The mass showed hypervascularity on enhanced computed tomography (CT), significantly increased 18F-fluorodeoxyglucose uptake on positron emission tomography (PET)/CT, and slightly increased somatostatin receptor (SSTR) expression on 68Ga-DOTATATE PET/CT, suggesting no distant metastases and subdiagnoses such as pancreatic PGL, NET, or primary tumor. Intraoperative pathology suggested lymphatic hyperplasia, and only simple tumor resection was performed. The patient was diagnosed with the hyaline vascular variant of CD, which was confirmed by postoperative immunohistochemistry. The patient was discharged successfully, and no recurrence was observed on regular review. CONCLUSION: High glucose uptake and slightly elevated SSTR expression are potentially new diagnostic features of CD of the pancreas.

20.
Thorac Cancer ; 13(15): 2106-2116, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35702992

RESUMO

BACKGROUND: To investigate the impact of station 3A lymph node dissection (LND) on overall survival (OS) and disease-free survival (DFS) in completely resected right-side non-small-cell lung cancer (NSCLC) patients. METHODS: A total of 1661 cases with completely resected right-side NSCLC were included. Propensity score matching (PSM) was performed to minimize selection bias, and a logistic regression model was conducted to investigate the risk factors associated with station 3A lymph node metastasis (LNM). The Kaplan-Meier method and Cox proportional hazards model were used to evaluate the impact of station 3A LND on survival. RESULTS: For the entire cohort, 503 patients (30.3%) underwent station 3A LND. Of those, 11.3% (57/503) presented station 3A LNM. Univariate and multivariate logistic analyses showed that station 10 LNM, tumor location, and the number of resected lymph nodes were independent risk factors associated with station 3A LNM. Before PSM, patients with station 3A LND had worse 5-year OS (p = 0.002) and DFS (p = 0.011), and more drainage on postoperative day 1 (p = 0.041) than those without. After PSM, however, station 3A LND was not associated with the 5-year OS (65.7% vs. 63.6%, p = 0.432) or DFS (57.4% vs. 56.0%, p = 0.437). The multivariate analysis further confirmed that station 3A LND was not a prognostic factor (OS, p = 0.361; DFS, p = 0.447). CONCLUSIONS: Station 3A LND could not improve long-term outcomes and it was unnecessary to dissect station 3A lymph nodes during surgery of right-side NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos
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