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1.
BMC Surg ; 24(1): 145, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734631

RESUMO

BACKGROUND: Delayed gastric emptying (DGE) commonly occurs after pancreaticoduodenectomy (PD). Risk factors for DGE have been reported in open PD but are rarely reported in laparoscopic PD (LPD). This study was designed to evaluate the perioperative risk factors for DGE and secondary DGE after LPD in a single center. METHODS: This retrospective cohort study included patients who underwent LPD between October 2014 and April 2023. Demographic data, preoperative, intraoperative, and postoperative data were collected. The risk factors for DGE and secondary DGE were analyzed. RESULTS: A total of 827 consecutive patients underwent LPD. One hundred and forty-two patients (17.2%) developed DGE of any type. Sixty-five patients (7.9%) had type A, 62 (7.5%) had type B, and the remaining 15 (1.8%) had type C DGE. Preoperative biliary drainage (p = 0.032), blood loss (p = 0.014), and 90-day any major complication with Dindo-Clavien score ≥ III (p < 0.001) were independent significant risk factors for DGE. Seventy-six (53.5%) patients were diagnosed with primary DGE, whereas 66 (46.5%) patients had DGE secondary to concomitant complications. Higher body mass index, soft pancreatic texture, and perioperative transfusion were independent risk factors for secondary DGE. Hospital stay and drainage tube removal time were significantly longer in the DGE and secondary DGE groups. CONCLUSION: Identifying patients at an increased risk of DGE and secondary DGE can be used to intervene earlier, avoid potential risk factors, and make more informed clinical decisions to shorten the duration of perioperative management.


Assuntos
Esvaziamento Gástrico , Laparoscopia , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Humanos , Pancreaticoduodenectomia/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso , Fatores de Risco , Esvaziamento Gástrico/fisiologia , Gastroparesia/etiologia , Gastroparesia/epidemiologia , Adulto
2.
J Med Chem ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713486

RESUMO

CARM1, belonging to the protein arginine methyltransferase (PRMT) family, is intricately associated with the progression of cancer and is viewed as a promising target for both cancer diagnosis and therapy. However, the number of specific and potent CARM1 inhibitors is limited. We herein discovered a CARM1 inhibitor, iCARM1, that showed better specificity and activity toward CARM1 compared to the known CARM1 inhibitors, EZM2302 and TP-064. Similar to CARM1 knockdown, iCARM1 suppressed the expression of oncogenic estrogen/ERα-target genes, whereas activated type I interferon (IFN) and IFN-induced genes (ISGs) in breast cancer cells. Consequently, iCARM1 potently suppressed breast cancer cell growth both in vitro and in vivo. The combination of iCARM1 with either endocrine therapy drugs or etoposide demonstrated synergistic effects in inhibiting the growth of breast tumors. In summary, targeting CARM1 by iCARM1 effectively suppresses breast tumor growth, offering a promising therapeutic approach for managing breast cancers in clinical settings.

3.
Sci Rep ; 14(1): 8389, 2024 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600093

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to most chemotherapy drugs, leading to poor chemotherapy efficacy. Recently, Trametinib and Palbociclib have promising prospects in the treatment of pancreatic cancer. This article aims to explore the effects of Trametinib on pancreatic cancer and address the underlying mechanism of resistance as well as its reversal strategies. The GDSC (Genomics of Drug Sensitivity in Cancer) and CTD2 (Cancer Target Discovery and Development) were utilized to screen the potential drug candidate in PDAC cell lines. The dose-increase method combined with the high-dose shock method was applied to induce the Trametinib-resistant PANC-1 and MIA PaCa-2 cell lines. The CCK8 proliferation assay, colony formation assay, flow cytometry, and western blot were conducted to verify the inhibitory effect of Trametinib and Palbociclib. RNA-seq was performed in resistant PDAC cell lines to find the differential expression genes related to drug resistance and predict pathways leading to the reversal of Trametinib resistance. The GDSC and CTD2 database screening revealed that Trametinib demonstrates a significant inhibitory effect on PDAC. We found that Trametinib has a lower IC50 than Gemcitabine in PDAC cell lines. Both Trametinib and Gemcitabine can decrease the proliferation capacity of pancreatic cells, induce cell cycle arrest, and increase apoptosis. Simultaneously, the phosphorylation of the AKT and ERK pathways were inhibited by the treatment of Trametinib. In addition, the RNA-seq of Trametinib-induced resistance PDAC cell lines reveals that the cyclin-dependent kinase (CDK)-RB-E2F regulatory axis and G2/M DNA damage checkpoint might lead the drug resistance. Besides, the combination of Trametinib with Palbociclib could inhibit the proliferation and cell cycle of both resistant cells lines and also restore the sensitivity of drug-resistant cells to Trametinib. Last but not least, the interferon-α and interferon-γ expression were upregulated in resistance cell lines, which might lead to the reversal of drug resistance. The study shows Trametinib has a critical inhibitory effect on PDAC. Besides, the combination of Trametinib with Palbociclib can inhibit the proliferation of PDAC-resistant cells.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Gencitabina , Proliferação de Células , Linhagem Celular Tumoral , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Ciclo Celular , Quinases de Proteína Quinase Ativadas por Mitógeno , Quinase 4 Dependente de Ciclina
4.
Technol Health Care ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38669496

RESUMO

BACKGROUND: Cerebral examination via CTA is always the first choice for patients with unexpected brain injury or different types of brain lesions to detect ruptured hemangiomas, vascular infarcts, or other brain tissue lesions. OBJECTIVE: This study innovated the acrylic gauge with five eccentric circles for computed tomography angiography (CTA) analysis to optimize the spatial resolution via Taguchi's methodology. METHODS: The customized gauge was revised from the V-shaped slit gauge and transferred into five eccentric circles' slit gauge. The gauge was assembled with another six acrylic layers to simulate the human head. Taguchi's L18 orthogonal array was adopted to optimize the spatial resolution of CTA imaging quality. In doing so, six essential factors of CTA are kVp, mAs, spiral rotation pitch, FOV, rotation time of the CT and reconstruction filter, and each factor has either two or three levels to organize into eighteen combinations to simulate the full factor combination of 486 (21 × 35 = 486) times according to Taguchi's recommendation. Three well-trained radiologists ranked the gauge's 18 CTA scanned imaging qualities according to contrast, sharpness, and spatial resolution and derived the unique fish-bone-plot of six factors for further analysis. The optimal factor combination of CTA was proven by follow-up verification and ANOVA to obtain this study's dominant or minor factor. RESULTS: The optimal factor combination of CTA was A2 (120 kVp), B3 (200 mAs), C1 (Pitch 0.6), D2 (FOV 220 mm2), E1 (rotation time 0.33 s), and F3 (Brain sharp, UC). Furthermore, deriving a quantified MDD (minimum detectable difference) to imply the spatial resolution of CTA, a semiauto profile analysis program run in MATLAB and OriginPro was recommended to evaluate the MDD and to suppress the manual error in calculation. Eventually, the derived MDDs of the conventional and optimal factor combinations of CTA were 2.35 and 2.26 mm, respectively, in this study. CONCLUSION: Taguchi's methodology was found applicable for quantifying the CTA imaging quality in practical applications.

5.
J Gastrointest Surg ; 28(4): 474-482, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583898

RESUMO

BACKGROUND: The fistula risk score (FRS) is the widely acknowledged prediction model for clinically relevant postoperative pancreatic fistula (CR-POPF). In addition, the alternative FRS (a-FRS) and updated alternative FRS (ua-FRS) have been developed. This study performed external validation and comparison of these 3 models in patients who underwent laparoscopic pancreaticoduodenectomy (LPD) with Bing's pancreaticojejunostomy. METHODS: The FRS total points and predictive probabilities of a-FRS and ua-FRS were retrospectively calculated using patient data from a completed randomized controlled trial. Postoperative pancreatic fistula (POPF) and CR-POPF were defined according to the 2016 International Study Group of Pancreatic Surgery criteria. The correlations of the 4 risk items of the FRS model with CR-POPF and POPF were analyzed and represented using the Cramer V coefficient. The performance of the 3 models was measured using the area under the curve (AUC) and calibration plot and compared using the DeLong test. RESULTS: This study enrolled 200 patients. Pancreatic texture and pathology had discrimination for CR-POPF (Cramer V coefficient: 0.180 vs 0.167, respectively). Pancreatic duct diameter, pancreatic texture, and pathology had discrimination for POPF (Cramer V coefficient: 0.357 vs 0.322 vs 0.257, respectively). Only the calibration of a-FRS predicting CR-POPF was good. The differences among the AUC values of the FRS, a-FRS, and ua-FRS were not statistically significant (CR-POPF: 0.687 vs 0.701 vs 0.710, respectively; POPF: 0.733 vs 0.741 vs 0.750, respectively). After recalibrating, the ua-FRS got sufficient calibration, and the AUC was 0.713 for predicting CR-POPF. CONCLUSION: For LPD cases with Bing's pancreaticojejunostomy, the 3 models predicted POPF with better discrimination than predicting CR-POPF. The recalibrated ua-FRS had sufficient discrimination and calibration for predicting CR-POPF.


Assuntos
Laparoscopia , Fístula Pancreática , Humanos , Fístula Pancreática/etiologia , Fístula Pancreática/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticojejunostomia/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Laparoscopia/efeitos adversos
6.
Nucleic Acids Res ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676947

RESUMO

Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits cancer cell growth in vitro and tumorigenesis in vivo. Targeting CARM1-mediated GATAD2A/2B methylation with CARM1 specific inhibitors potently inhibit breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires arginine methylation established by CARM1 on a key chromatin remodeler, and targeting such methylation might represent a promising therapeutic avenue in the clinic.

7.
World J Surg Oncol ; 22(1): 43, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38317188

RESUMO

BACKGROUND: Textbook oncologic outcomes (TOO) have been used to evaluate long-term oncologic outcomes for patients after pancreaticoduodenectomy (PD) but not laparoscopic pancreaticoduodenectomy (LPD). The aim of the study was to assess the prognostic value of TOO for patients with pancreatic head cancer undergoing LPD and discuss the risk factors associated with achieving TOO. METHODS: Patients with pancreatic head cancer who underwent LPD in West China Hospital from January 2015 to May 2022 were consecutively enrolled. TOO was defined as achieving R0 resection, examination of ≥ 12 lymph nodes, no prolonged length of stay, no 30-day readmission/death, and receiving adjuvant chemotherapy. Survival analysis was used to determine the prognostic value of a TOO on overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify the risk factors of a TOO. The rates of a TOO and of each indicator were compared in patients who suffered or not from delayed gastric emptying (DGE). RESULTS: A total of 44 (25.73%) patients achieved TOO which was associated with improved median OS (TOO 32 months vs. non-TOO 20 months, P = 0.034) and a better RFS (TOO 19 months vs. non-TOO 13 months, P = 0.053). Patients suffering from DGE [odds ratio (OR) 4.045, 95% CI 1.151-14.214, P = 0.029] were independent risk factors for TOO. In addition, patients with DGE after surgery had a significantly lower rate of TOO (P = 0.015) than patients without DGE. CONCLUSIONS: As there were significant differences between patients who achieved TOO or not, TOO is a good indicator for long-term oncologic outcomes in patients with pancreatic head cancer after undergoing LPD. DGE is the risk factor for achieving TOO, so it is important to prevent the DGE after LPD to improve the rate of TOO.


Assuntos
Laparoscopia , Neoplasias Pancreáticas , Humanos , Pancreaticoduodenectomia/efeitos adversos , Pâncreas/cirurgia , Prognóstico , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
8.
Sci Rep ; 14(1): 726, 2024 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184756

RESUMO

Intra-abdominal adhesions have consistently posed a challenge for surgeons during procedures. This study aims to investigate the feasibility of utilizing indocyanine green (ICG) in conjunction with near-infrared imaging for the detection of intra-abdominal adhesions. In vitro, we analyzed factors affecting ICG fluorescence. We divided SD rats into groups to study ICG excretion in different digestive tract regions. Additionally, we reviewed surgical videos from previous cholecystectomy cases, categorizing them by ICG injection timing and assessing fluorescence imaging in various digestive tract regions. Finally, we preoperatively injected ICG into two cholecystectomized patients with abdominal adhesions, guiding intraoperative adhesiolysis with near-infrared fluorescence imaging. In vitro, we observed a significant influence of protein and ICG concentrations on ICG fluorescence intensity. Our rat experiments unveiled a strong and highly significant correlation (Kendall's tau-b = 1, P < 0.001) between the timing of ICG injection and the farthest point of intestinal fluorescence. A retrospective case analysis further validated this finding (Kendall's tau-b = 0.967, P < 0.001). Under the guidance of fluorescence navigation, two cholecystectomized patients with intra-abdominal adhesions successfully underwent adhesiolysis, and no postoperative complications occurred. The intraoperative combination of ICG with near-infrared fluorescence imaging effectively enhances the visibility of the liver, bile ducts, and various segments of the gastrointestinal tract while providing real-time navigation. This real-time fluorescence guidance has the potential to aid surgeons in the dissection of intra-abdominal adhesions.


Assuntos
Verde de Indocianina , Cirurgiões , Humanos , Animais , Ratos , Ratos Sprague-Dawley , Estudos Retrospectivos , Dissecação
9.
BMJ Open ; 14(1): e078092, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38199635

RESUMO

INTRODUCTION: Postoperative pancreatic fistula (POPF) remains one of the most severe complications of laparoscopic pancreaticoduodenectomy (LPD). Theoretically, transecting the pancreatic neck more distally has both advantages (more blood supply, and more central pancreatic duct) and disadvantages (maybe smaller the pancreatic duct) in preventing POPF. This theoretical contradiction pushed us to organise this trial to explore the impact of the level of pancreatic transection in clinical practice. We conduct this randomised trial with the hypothesis that extended pancreatic neck transection has superiority to conventional pancreatic neck transection. METHODS AND ANALYSIS: The LPDEXCEPT (Extended pancreatic neck transection versus conventional pancreatic neck transection during laparoscopic pancreaticoduodenectomy) trial is a multicentre, randomised-controlled, open-label, superiority trial in 4 centres whose annual surgical volume for LPD is more than 25 cases with pancreatic surgeons who had completed their learning curve. A total of 154 patients who meet the inclusive and exclusive criteria are randomly allocated to the extended pancreatic neck transection group or conventional pancreatic neck transection group in a 1:1 ratio. The stratified randomised block design will be applied, with stratified factors are surgical centre and the diameter of the main pancreatic duct measured by preoperative CT scan (preMPD). The primary outcome is the incidence of the clinically relevant pancreatic fistula. ETHICS AND DISSEMINATION: Ethics Committee on Biomedical Research of West China Hospital of Sichuan University has approved this trial in March 2023 (approval no. 2023-167). Results of this trial will be published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: NCT05808894.


Assuntos
Laparoscopia , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/efeitos adversos , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Pâncreas , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
10.
Int J Surg ; 110(3): 1441-1449, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38079605

RESUMO

BACKGROUND: Various surgical skills lead to differences in patient outcomes and identifying poorly skilled surgeons with constructive feedback contributes to surgical quality improvement. The aim of the study was to develop an algorithm for evaluating surgical skills in laparoscopic cholecystectomy based on the features of elementary functional surgical gestures (Surgestures). MATERIALS AND METHODS: Seventy-five laparoscopic cholecystectomy videos were collected from 33 surgeons in five hospitals. The phase of mobilization hepatocystic triangle and gallbladder dissection from the liver bed of each video were annotated with 14 Surgestures. The videos were grouped into competent and incompetent based on the quantiles of modified global operative assessment of laparoscopic skills (mGOALS). Surgeon-related information, clinical data, and intraoperative events were analyzed. Sixty-three Surgesture features were extracted to develop the surgical skill classification algorithm. The area under the receiver operating characteristic curve of the classification and the top features were evaluated. RESULTS: Correlation analysis revealed that most perioperative factors had no significant correlation with mGOALS scores. The incompetent group has a higher probability of cholecystic vascular injury compared to the competent group (30.8 vs 6.1%, P =0.004). The competent group demonstrated fewer inefficient Surgestures, lower shift frequency, and a larger dissection-exposure ratio of Surgestures during the procedure. The area under the receiver operating characteristic curve of the classification algorithm achieved 0.866. Different Surgesture features contributed variably to overall performance and specific skill items. CONCLUSION: The computer algorithm accurately classified surgeons with different skill levels using objective Surgesture features, adding insight into designing automatic laparoscopic surgical skill assessment tools with technical feedback.


Assuntos
Colecistectomia Laparoscópica , Laparoscopia , Humanos , Gestos , Laparoscopia/métodos , Colecistectomia Laparoscópica/métodos , Dissecação , Algoritmos , Competência Clínica
11.
Front Immunol ; 14: 1284334, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37942324

RESUMO

Objective: The aim of this study was to explore the safety and efficacy of multiple peptide-pulsed autologous dendritic cells (DCs) combined with cytotoxic T lymphocytes (CTLs) in patients with cancer. Methods: Five patients diagnosed with cancer between November 2020 and June 2021 were enrolled and received DC-CTLs therapy. Peripheral blood was collected and antigenic peptides were analyzed. The phenotype and function of DC-CTLs and the immune status of patients were detected using flow cytometry or IFN-γ ELISPOT analysis. Results: DCs acquired a mature phenotype and expressed high levels of CD80, CD86, CD83, and HLA-DR after co-culture with peptides, and the DC-CTLs also exhibited high levels of IFN-γ. Peripheral blood mononuclear cells from post-treatment patients showed a stronger immune response to peptides than those prior to treatment. Importantly, four of five patients maintained a favorable immune status, of which one patient's disease-free survival lasted up to 28.2 months. No severe treatment-related adverse events were observed. Conclusion: Our results show that multiple peptide-pulsed DCs combined with CTLs therapy has manageable safety and promising efficacy for cancer patients, which might provide a precise immunotherapeutic strategy for cancer.


Assuntos
Neoplasias , Linfócitos T Citotóxicos , Humanos , Leucócitos Mononucleares , Neoplasias/terapia , Peptídeos , Células Dendríticas
12.
Molecules ; 28(22)2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38005393

RESUMO

A novel gas-pressurized (GP) torrefaction method at 250 °C has recently been developed that realizes the deep decomposition of cellulose in lignocellulosic solid wastes (LSW) to as high as 90% through deoxygenation and aromatization reactions. However, the deoxygenation and aromatization mechanisms are currently unclear. In this work, these mechanisms were studied through a developed molecular structure calculation method and the GP torrefaction of pure cellulose. The results demonstrate that GP torrefaction at 250 °C causes 47 wt.% of mass loss and 72 wt.% of O removal for cellulose, while traditional torrefaction at atmospheric pressure has almost no impact on cellulose decomposition. The GP-torrefied cellulose is determined to be composed of an aromatic furans nucleus with branch aliphatic C through conventional characterization. A molecular structure calculation method and its principles were developed for further investigation of molecular-level mechanisms. It was found 2-ring furans aromatic compound intermediate is formed by intra- and inter-molecular dehydroxylation reactions of amorphous cellulose, and the removal of O-containing function groups is mainly through the production of H2O. The three-ring furans aromatic compound intermediate and GP-torrefied cellulose are further formed through the polymerization reaction, which enhances the removal of ketones and aldehydes function groups in intermediate torrefied cellulose and form gaseous CO and O-containing organic molecules. A deoxygenation and aromatization mechanism model was developed based on the above investigation. This work provides theoretical guidance for the optimization of the gas-pressurized torrefaction method and a study method for the determination of molecular-level structure and the mechanism investigation of the thermal conversion processes of LSW.

13.
Protein Pept Lett ; 30(12): 992-1000, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38013437

RESUMO

OBJECTIVES: We aim to investigate the regulatory mechanisms of miR-455-5p/SOCS3 pathway that underlie the proliferation, migration, and invasion of triple-negative breast cancer (TNBC) cells. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-455-5p expression in breast cancer tissues and cell lines. CCK8 and Transwell assays were conducted to assess the effects of miR-455-5p on breast cancer line proliferation, migration, and invasion. SOCS3 expression level in breast cancer tissues and cell lines was determined by qPCR and western blotting. The targeting relationship between miR-455-5p and SOCS3 was determined by dual luciferase reporter gene assay in different breast cancer cell lines. Finally, the upstream and downstream regulatory association between miR-455-5p and SOCS3 was confirmed in breast cancer cells by CCK8, western blot, and Transwell assays. RESULTS: MiR-455-5p expression was up-regulated in breast cancer tissues; miR-455-5p regulates TNBC proliferation, migration, and invasion of TNBC. SOCS3 was the direct target of miR-455-5p and was down-regulated in breast cancer. Interference with SOCS3 reversed the inhibitory effect of the miR-455-5p inhibitor on breast cancer cells' malignant potential. CONCLUSION: MiR-455-5p promotes breast cancer progression by targeting the SOCS3 pathway and may be a potential therapeutic target for breast cancer.


Assuntos
MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , MicroRNAs/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Células MCF-7 , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo
14.
Mol Med ; 29(1): 127, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710176

RESUMO

BACKGROUND: Recent years have witnessed impressive growth in applying natural medicine in tumor treatment. Saffron is reported to elicit an inhibitory property against BC. Herein, we sought to explore the specific components and mechanistic basis of saffron's anti-breast carcinoma (BC) function. METHODS: Bioinformatics analysis was employed to analyze saffron components' anti-BC activity and screen the corresponding target genes involved in BC. Then, the roles of the main saffron ingredient quercetin in the activity of BC cells were examined using CCK-8, MTS, flow cytometry, colony formation, Transwell, and Gelatin zymogram assays. Additionally, the interactions among Quercetin, EET, and Stat3 were assessed by immunofluorescence and Western blot, and LC-MS/MS determined the levels of AA, EETs, and CYP3A. Finally, BC xenograft mouse models were established to verify the anti-BC function of Quercetin in vivo. RESULTS: Quercetin, the main active component of saffron, inhibited BC progression. Quercetin suppressed BC cell growth, migration, and invasion and inhibited CYP3A4 expression and activity in BC. Mechanistically, Quercetin down-regulated CYP3A4 to block the nuclear translocation of Stat3 by decreasing the metabolization of AA to EETs, thereby alleviating BC. Moreover, exogenously added EETs counteracted the anti-tumor effect of Quercetin on BC. Quercetin also inhibited the tumor growth of tumor-bearing nude mice. CONCLUSION: Quercetin could inhibit the activity of CYP3A to down-regulate AA metabolites EETs, consequently hampering p-Stat3 and nuclear translocation, thus impeding BC development.


Assuntos
Produtos Biológicos , Neoplasias da Mama , Humanos , Animais , Camundongos , Feminino , Ácido Araquidônico , Citocromo P-450 CYP3A , Quercetina/farmacologia , Quercetina/uso terapêutico , Cromatografia Líquida , Camundongos Nus , Espectrometria de Massas em Tandem , Neoplasias da Mama/tratamento farmacológico
15.
BMC Surg ; 23(1): 219, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37550646

RESUMO

BACKGROUND: The use of single-incision plus one-port laparoscopic pancreaticoduodenectomy (SILPD + 1) has been never reported, and its safety and efficacy remain unknown. This study aimed to evaluate the short-term outcomes of SILPD + 1 compared with those of conventional laparoscopic pancreaticoduodenectomy (CLPD). METHOD: Fifty-seven cases of laparoscopic pancreaticoduodenectomy (LPD) were performed between November 2021, and March 2022. Among them, 10 cases of LPD were performed using a single-incision plus one-port device. Based on the same inclusion and exclusion criteria, 47 cases of LPD performed using traditional 5-trocar were included as a control group. The patient's demographic characteristics, intraoperative, and postoperative variables were prospectively collected and retrospectively analyzed. RESULTS: Three men and seven women were included in the SILPD + 1 group. All baseline parameters of both groups were comparable, except for age. Patients were younger in the SILPD + 1 group (47.2 ± 18.3 years vs. 60.6 ± 11.7 years, P = 0.05) than that in the CLPD group. Compared with the CLPD group, median operation time (222.5 (208.8-245.0) vs. 305.0 (256.0-37.0) min, P < 0.001) was shorter, median postoperative VAS scores on days 1-3 were lower, and median cosmetic score (21.0 (19.0-23.5) vs. 17.0 (16.0-20.0), P = 0.026) was higher one month after the surgery in the SILPD + 1 group. The estimated blood loss, conversion rate, blood-transfusion rate, exhaust time, time of drainage tube removal, postoperative hospital stays, and perioperative complications were comparable between the two groups. CONCLUSION: In a high-volume LPD center, SILPD + 1 is safe and feasible for well-selected patients without increasing the operation time and complications. It even has the advantages of reduced postoperative pain and improved cosmetic results.


Assuntos
Laparoscopia , Pancreaticoduodenectomia , Masculino , Humanos , Feminino , Pancreaticoduodenectomia/métodos , Estudos Retrospectivos , Tempo de Internação , Anastomose Cirúrgica , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia
16.
FEBS Open Bio ; 13(11): 2124-2146, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37596964

RESUMO

Ras homolog gene family member V (RHOV) is an atypical Rho GTPase that participates in various important cellular processes. Although RHOV has been identified to play an oncogenic role in lung cancer and triple-negative breast cancer, its role in other types of tumors remains unknown. In this study, we investigated the expression of RHOV in pan-cancer analysis using The Cancer Genome Atlas (TCGA) and Gene-Tissue Expression datasets. RHOV mRNA levels were dysregulated in several types of tumors. RHOV expression was identified as an independent prognostic factor in 7 of 33 types of tumors; however, the relationship varied according to tumor type. Higher RHOV expression was associated with a favorable prognosis in kidney renal cell carcinoma and prostate adenocarcinoma, for which RHOV expression was downregulated, whereas RHOV expression was associated with a poor prognosis for patients with adenoid cystic carcinoma, lung adenocarcinoma, pancreatic ductal adenocarcinoma, skin cutaneous melanoma, and uveal melanoma with upregulated RHOV expression. Furthermore, RHOV expression was associated with various clinicopathological parameters in these tumors. RHOV expression showed varied associations with different types of tumor-infiltrating immune cells and demonstrated a potential impact on the response to immunotherapy depending on the cancer type. Additionally, functional enrichment analysis of RHOV-related genes demonstrated a role in a wide range of developmental and immune-related processes. This study provides valuable insights into the role of RHOV in pan-cancer development, indicating its role as a tumor suppressor or oncogene according to the cancer type and tumor microenvironment.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Pulmonares , Melanoma , Neoplasias Pancreáticas , Neoplasias Cutâneas , Humanos , Masculino , Prognóstico , Microambiente Tumoral/genética , Melanoma Maligno Cutâneo
17.
World Neurosurg ; 178: e766-e772, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37562680

RESUMO

OBJECTIVE: We investigated the correlation between bone cement distribution and adjacent vertebral fractures (AVFs) after percutaneous vertebroplasty (PVP). METHODS: We retrospectively analyzed patients who underwent single-segment PVP for osteoporotic compression fractures in our hospital from January 2016 to January 2021 and divided the patients into 2 groups, A and B, on the basis of the criterion of whether there were AVFs of the operated vertebrae within 1 year after surgery. We compared the general data of the 2 groups, assessed the ability of 3 simple X-ray-based evaluation methods to predict the occurrence of AVF within 1 year after surgery and derived a simple and accurate evaluation method. RESULTS: A total of 570 patients were included in this study: 511 patients in group A and 59 patients in group B. There were no statistical differences in the general data such as age, gender, and fracture site between the 2 groups. The posterior-anterior (PA), lateral (LAT), and PA and LAT methods showed receiver operating characteristic curve (ROC) predicted postoperative AVF of 0.611, 0.691, and 0.714, respectively. The difference between the area under curve (AUC) of the PA method and LAT method was statistically significant (P = 0.0307), the difference between the AUC of PA method and PA and LAT method was statistically significant (P < 0.001), and the difference between the AUC of LAT method and PA and LAT method was not statistically significant (P = 0.3308).There was no statistical difference between the 2 groups of patients with PA method point of 1 and statistically different between patients with points of 2 and 3. There was statistical difference in points of 1, 2 and 3 in the LAT method between the 2 groups. There was a positive correlation between cement distribution scores and AVF by linear regression analysis of the 3 evaluation methods. CONCLUSIONS: The 3 evaluation methods reliably predict AVF after PVP, with the LAT method, PA and LAT method being more predictive than the PA method, but the LAT method is simpler, with bone cement being widely distributed after crossing the midline in the PA method and contact with the upper and lower end plates in the LAT method being a risk factor for AVF.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Vertebroplastia/efeitos adversos , Vertebroplastia/métodos , Cimentos Ósseos , Estudos Retrospectivos , Correlação de Dados , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/complicações , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/epidemiologia , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Fraturas por Compressão/complicações , Resultado do Tratamento
18.
Front Oncol ; 13: 1113490, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37519815

RESUMO

Background: Laparoscopic transduodenal ampullectomy (LTDA) is a function-preserving surgery for pre-malignant tumors of the ampulla of Vater (AoV). However, it is technically challenging, and only a few case reports of LTDA are available in the literature. Methods: A total of 43 cases of pre-malignant tumors of AoV were operated in West China Hospital, Sichuan University between January 2017 and July 2022. Among these patients, 9 patients (group 1) underwent LTDA, 19 patients (group 2) underwent laparoscopic pancreaticoduodenectomy (LPD), and 15 patients (group 3) underwent open transduodenal ampullectomy (OTDA). Prospective collection and retrospective analysis of the demographic characteristics, intraoperative variables, and postoperative variables were carried out. Results: The patients in the three groups were comparable in terms of sex, age, body mass index, tumor size, and preoperative blood tests. In comparison to the patients in group 2, the patients in group 1 were found to require less operative time (159.7 ± 47.5 min vs. 298.1 ± 62.6, p < 0.01) and suffered lower blood losses (23.3 ± 16.7 ml vs. 156.8 ± 112.1, p = 0.002) and complications. Moreover, the postoperative hospital stays (POHS) were significantly shorter for patients in group 1 (9.0 ± 5.3 days vs. 15.5 ± 7.3 days, p = 0.04). Compared to patients who underwent OTDA, the patients in LTDA suffered from less blood loss. The operative time and post-operative details were comparable. Conclusion: Therefore, LTDA was found to be safe and feasible in the setting of pre-malignant tumors of AoV in well-selected patients. However, multidisciplinary preoperative planning is essential before the surgery.

19.
ACS Omega ; 8(18): 16241-16250, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37179651

RESUMO

Alkali and alkaline earth metals (AAEMs) in agricultural organic solid waste (AOSW) contribute to the fouling and slagging during its combustion. In this study, a novel flue gas-enhanced water leaching (FG-WL) method using flue gas as the heat and CO2 source was proposed for effective AAEM removal from AOSW before combustion. The removal rate of AAEMs by FG-WL was significantly superior to that by conventional water leaching (WL) under the same pretreatment conditions. Furthermore, FG-WL also obviously reduced the release of AAEMs, S, and Cl during AOSW combustion. The ash fusion temperatures of the FG-WL-treated AOSW was higher than that of WL. The fouling and slagging tendency of AOSW greatly decreased through FG-WL treatment. Thus, FG-WL is a simple and feasible method for AAEM removal from AOSW and suppressing fouling and slagging during its combustion. Besides, it also provides a new pathway for the resource utilization of power plant flue gas.

20.
BMC Surg ; 23(1): 140, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37208624

RESUMO

BACKGROUND: Solid pseudopapillary tumor (SPT) of the pancreas is a rare low-grade malignant tumor. Here, we aimed to determine the safety and feasibility of laparoscopic parenchyma-sparing pancreatectomy for SPT located in the pancreatic head. METHODS: From July 2014 to February 2022, 62 patients with SPT located in the pancreatic head were operated laparoscopically in two institutions. These patients were divided into two groups according to the operative strategy: laparoscopic parenchyma-sparing pancreatectomy (27 patients, group 1) and laparoscopic pancreaticoduodenectomy (35 patients, group 2). The clinical data were retrospectively collected and analyzed in terms of demographic characteristics, perioperative variables, and long-term follow-up outcomes. RESULTS: The demographic characteristics of the patients in the two groups were comparable. Compared to the patients in group 2, those in group 1 required less operative time (263.4 ± 37.2 min vs. 332.7 ± 55.6 min, p < 0.001) and experienced less blood loss (105.1 ± 36.5mL vs. 188.3 ± 150.7 mL, p < 0.001). None of the patients in group 1 had tumor recurrence or metastasis. However, 1 (2.5%) patient in group 2 showed liver metastasis. CONCLUSION: Laparoscopic parenchyma-sparing pancreatectomy is a safe and feasible approach for SPT located in the pancreatic head, with favorable long-term functional and oncological results.


Assuntos
Laparoscopia , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Resultado do Tratamento , Pâncreas/cirurgia , Pâncreas/patologia , Pancreatectomia/métodos , Laparoscopia/métodos
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