RESUMO
Esophageal squamous cell carcinoma (ESCC) commonly has aggressive properties and a poor prognosis. Investigating the molecular mechanisms underlying the progression of ESCC is crucial for developing effective therapeutic strategies. Here, by performing transcriptome sequencing in ESCC and adjacent normal tissues, we find that E74-like transcription factor 4 (ELF4) is the main upregulated transcription factor in ESCC. The results of the immunohistochemistry show that ELF4 is overexpressed in ESCC tissues and is significantly correlated with cancer staging and prognosis. Furthermore, we demonstrate that ELF4 could promote cancer cell proliferation, migration, invasion, and stemness by in vivo assays. Through RNA-seq and ChIP assays, we find that the stemness-related gene fucosyltransferase 9 ( FUT9) is transcriptionally activated by ELF4. Meanwhile, ELF4 is verified to affect ESCC cancer stemness by regulating FUT9 expression. Overall, we first discover that the transcription factor ELF4 is overexpressed in ESCC and can promote ESCC progression by transcriptionally upregulating the stemness-related gene FUT9.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/metabolismo , Neoplasias Esofágicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismoRESUMO
Steroid hormones have been reported to be associated with endocrine system diseases. This paper proposes a novel procedure of deep eutectic solvent (DES)-assisted liquid-liquid extraction (LLE) to extract six steroid hormones (including cortisone, cortisol, androstenedione, testosterone, 17-hydroxyprogesterone, and progesterone) from serum coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of five types of L-proline, choline chloride, and citric acid-based DESs were tailored; the DES from L-proline and ethylene glycol at a molar ratio of 1:4 with 20 % acetonitrile was selected as the best-fit assisted solvent for the six steroid hormones compared with other DESs. The parameters for extraction by selected DES were optimized using Box-Behnken design (BBD), and the optimal extraction conditions are 200 µL of acetonitrile, 100 µL of the sample, and 80 µL of DES. Under optimum conditions, the method has good linear calibration ranges (between 0.07 ng mL-1 and 600 ng mL-1), correlation coefficients of determination (r2>0.99), and low limits of quantification (between 0.02 and 0.60 ng mL-1). The extraction recoveries were in the range of 81.84-114.43 %, and the intra-day and inter-day relative standard deviations (RSDs) were less than 10 %.In general, the DES-LC-MS/MS method is a simple and environmentally-friendly method, which can be complementary to the presently available methods for determining steroid hormones in serum.
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Solventes Eutéticos Profundos , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Limite de Detecção , Esteroides/análise , Extração Líquido-Líquido , Hidrocortisona/análise , Acetonitrilas/análise , Prolina , Cromatografia Líquida de Alta PressãoRESUMO
Transcription factor 3 (TCF3) is a member of the basic Helix - Loop - Helix (bHLH) transcription factor (TF) family and is encoded by the TCF3 gene (also known as E2A). It has been shown that TCF3 functions as a key transcription factor in the pathogenesis of several human cancers and plays an important role in stem cell maintenance and carcinogenesis. However, the effect of TCF3 in the progression of esophageal squamous cell carcinoma (ESCC) is poorly known. In our study, TCF3 was found to express highly and correlated with cancer stage and prognosis. TCF3 was shown to promote ESCC invasion, migration, and drug resistance both from the results of in vivo and in vitro assays. Moreover, further studies suggested that TCF3 played these roles through transcriptionally regulating Inhibitor of DNA binding 1(ID1). Notably, we also found that TCF3 or ID1 was associated with ESCC stemness. Furthermore, TCF3 was correlated with the expression of cancer stemness markers CD44 and CD133. Therefore, maintaining cancer stemness might be the underlying mechanism that TCF3 transcriptionally regulated ID1 and further promoted ESCC progression and drug resistance.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Carcinogênese , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Proteína 1 Inibidora de Diferenciação/genética , Fator 3 de Transcrição , Fatores de TranscriçãoRESUMO
Nonsmall cell lung cancer (NSCLC) is a major subtype of lung cancer, causing substantial cancer-related deaths worldwide. However, the molecular basis of NSCLC development and progression remains understudied. Recently, a circular RNA, circDLG1, has been implicated in carcinogenesis and cancer metastasis. Yet, how circDLG1 affects NSCLC progression has not been reported. Here this study aims to elucidate the role of circDLG1 in NSCLC. First, we found that circDLG1 was significantly upregulated in both the GEO dataset and NSCLC tissues. Next, we silenced the expression of circDLG1 in NSCLC cell lines. Knockdown of circDLG1 upregulated miR-144 and downregulated Protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), resulting in suppression of the proliferation activity and metastasis ability of NSCLC. In addition, circDLG1 knockdown significantly decreased the expression of the mesenchymal markers, proliferating cell nuclear antigen (PCNA), and N-cadherin, while increasing the expression level of E-cadherin. In conclusion, we demonstrate that circDLG1 promotes the pathogenesis and progression of NSCLC by regulating the miR-144/AKT/mTOR signaling axis, providing potential diagnostic and therapeutic targets for designing innovative treatment strategies.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , RNA Circular/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Oncogenes/genética , Proliferação de Células/genética , Linhagem Celular TumoralRESUMO
The present study was aimed to investigate whether Gasdermin D (GSDMD)-mediated pyroptosis participated in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (AKI), and to explore the role of caspase-1 and caspase-11 pyroptosis pathways in this process. The mice were divided into four groups: wild type (WT), WT-LPS, GSDMD knockout (KO) and KO-LPS. The sepsis-associated AKI was induced by intraperitoneal injection of LPS (40 mg/kg). Blood samples were taken to determine the concentration of creatinine and urea nitrogen. The pathological changes of renal tissue were observed via HE staining. Western blot was used to investigate the expression of pyroptosis-associated proteins. The results showed that the concentrations of serum creatinine and urea nitrogen in the WT-LPS group were significantly increased, compared with those in the WT group (P < 0.01); whereas serum creatinine and urea nitrogen in the KO-LPS group were significantly decreased, compared with those in the WT-LPS group (P < 0.01). HE staining results showed that LPS-induced renal tubular dilatation was mitigated in GSDMD KO mice. Western blot results showed that LPS up-regulated the protein expression levels of interleukin-1ß (IL-1ß), GSDMD and GSDMD-N in WT mice. GSDMD KO significantly down-regulated the protein levels of IL-1ß, caspase-11, pro-caspase-1, caspase-1(p22) induced by LPS. These results suggest that GSDMD-mediated pyroptosis is involved in LPS-induced sepsis-associated AKI. Caspase-1 and caspase-11 may be involved in GSDMD cleavage.
Assuntos
Injúria Renal Aguda , Caspases , Sepse , Animais , Camundongos , Caspase 1 , Caspases/metabolismo , Creatinina , Lipopolissacarídeos , Camundongos Knockout , Nitrogênio , Ureia , Gasderminas/metabolismoRESUMO
BACKGROUND: Cisplatin (DDP)-based chemotherapy is commonly adopted as the first-line treatment for patients with oesophageal squamous cell carcinoma (OSCC), but the high rate of drug resistance limits its clinical application and the underlying mechanisms at play remain unclear. The aims of this study were to elucidate the role of abnormal signal transmission and metabolism in the chemoresistance of OSCC under hypoxia and to identify targeted drugs that enhance the sensitivity of DDP chemotherapy. METHODS: Upregulated genes in OSCC were determined by RNA sequencing (RNA-seq), the Cancer Genome Atlas (TCGA) database, immunohistochemistry (IHC), real-time quantitative PCR (RT-qPCR), and western blotting (WB). The clinicopathological significance of insulin-like growth factor-I receptor (IGF1R), argininosuccinate synthetase 1 (ASS1), and pyrroline-5-carboxylate reductase 1 (PYCR1) in OSCC was analysed using tissue micriarray (TMA). Metabolic abnormalities were determined by untargeted metabolomics analysis. The DDP-resistance role of IGF1R, ASS1, and PYCR1 in OSCC was investigated in vitro and in vivo. RESULTS: Generally, tumour cells exist in a hypoxic microenvironment. By genomic profiling, we determined that IGF1R, as a receptor tyrosine kinase (RTK), was upregulated in OSCC under low-oxygen conditions. Clinically, enhanced IGF1R expression was associated with higher tumour stages and a poorer prognosis in OSCC patients, and its inhibitor, linsitinib, showed synergistic effects with DDP therapy in vivo and in vitro. Since oxygen-deprivation frequently lead to metabolic reprogramming, we further learned via metabolomics analysis that abnormal IGF1R pathways promoted the expression of metabolic enzymes ASS1 and PYCR1 by the transcriptional activity of c-MYC. In detail, enhanced expression of ASS1 promotes arginine metabolism for biological anabolism, whereas PYCR1 activates proline metabolism for redox balance, which maintains the proliferation ability of OSCC cells during DDP treatment under hypoxic conditions. CONCLUSION: Enhanced expression of ASS1 and PYCR1 via IGF1R pathways rewired arginine and proline metabolism, promoting DDP resistance in OSCC under hypoxia. Linsitinib targeting IGF1R signaling may lead to promising combination therapy options for OSCC patients with DDP resistance.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , Prolina/farmacologia , Linhagem Celular Tumoral , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Hipóxia , Arginina/farmacologia , Oxigênio , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Microambiente Tumoral , Receptor IGF Tipo 1RESUMO
BACKGROUND AND AIMS: This retrospective study aimed to evaluate the effect and safety of endoscopic submucosal dissection (ESD) for large laterally spreading lesions located in the descending duodenum based on multi-center experiences. METHODS: This multicentric retrospective study included 3 hospitals in China. Fifty-one patients with laterally spreading lesions of the duodenum who underwent ESD between February 2019 and December 2020 were enrolled. The en bloc resection rates, en bloc R0 resection rates, complication rates, and local recurrence after ESD were evaluated. RESULTS: Of the 51 patients, the median age was 62 years old (ranging from 37 to 76 years old); among them, 29 were male and 22 were female. The average lesion size was 2.3 cm (ranging from 1.5 to 4.0 cm). All 51 lesions achieved en bloc R0 resection successfully, with the procedure time ranging from 20 to 117 min (median: 45.5 min). The hospital length of stay ranged from 4 to 90 days (median: 8.0 d). Two patients experienced delayed bleeding 3 days after ESD and 2 other patients were diagnosed with delayed perforation. Tumor residual and local recurrence did not occur during a short follow-up period. CONCLUSIONS: ESD for laterally spreading lesions of the descending duodenum is feasible.
Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Ressecção Endoscópica de Mucosa/métodos , Estudos Retrospectivos , Neoplasias Colorretais/cirurgia , Mucosa Intestinal/cirurgia , Mucosa Intestinal/patologia , Duodeno/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND : There remain concerns regarding the technical feasibility of endoscopic resection for large gastrointestinal stromal tumors (GISTs), mainly relating to the risk of tumor rupture and the adequacy of the resection margins. This study aimed to evaluate the feasibility and therapeutic outcomes of the newly developed no-touch endoscopic full-thickness resection (NT-EFTR) technique for GISTs. METHODS : In this retrospective study, 92 patients with gastric GISTs undergoing NT-EFTR were included. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. RESULTS : The median tumor size was 2.5âcm and en bloc resection was achieved in all patients with negative surgical margins. The median time of the NT-EFTR procedure was 59.5 minutes. Large tumors (>â3.0âcm), extraluminal tumor growth pattern, and large gastric defects were significant contributors to long operative times. Patients were discharged within 4 days postoperatively. During follow-up, all patients were free from local recurrence and distant metastasis. CONCLUSIONS : NT-EFTR was a feasible method for the resection of gastric GISTs and can be expected to achieve complete radical resection. Large tumors with extraluminal growth and large gastric defects impact procedural difficulty.
Assuntos
Ressecção Endoscópica de Mucosa , Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Ressecção Endoscópica de Mucosa/métodos , Gastroscopia/métodosRESUMO
OBJECTIVES: Post-ESD esophageal stricture especially after wholly circumferential ESD remains an unresolved issue without ideal strategies. Our initiative novel self-control stricture-preventing water balloon may be an alternative. METHODS: Patients with esophageal neoplastic lesions expected to result in a whole circular mucosa defect after esophageal ESD from February 2018 to August 2020 were included in the study. We used a novel self-control stricture-preventing water balloon combined with oral prednisolone as preventive strategy for the enrolled patients. RESULTS: Thirty-seven patients (9 females and 28 males, patients aged 52 to 82 years) finished the 12-week treatment including steroid treatment and balloon placement. The median size of longitudinal diameter was 7 cm (range from 4 to 14 cm). All the lesions achieved curative resection and the median procedure time was 110 min (range 50 to 180 min). Balloons were found migration in 4 patients. As a result, there were 3 patients (8.1%) experienced stricture. Generally, patients could tolerate to balloons, only with mild uncomfortableness, such as occasional sore throat, cough, and retrosternal pain. In addition, during the follow-up period, no significant adverse events associated to oral steroid administration were observed and no recurrence was found. CONCLUSIONS: Our novel self-control stricture-preventing water balloon based on the oral steroid therapy is effective and safe. This strategy well prevents esophageal stricture after complete circumferential ESD.
Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Estenose Esofágica , Autocontrole , Masculino , Feminino , Humanos , Estenose Esofágica/etiologia , Estenose Esofágica/prevenção & controle , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Constrição Patológica/etiologia , Neoplasias Esofágicas/patologia , EsteroidesRESUMO
Renal tubular epithelial cells injury is one of the most important pathological features in hyperuricemic nephropathy (HN). However, the involvement of gasdermin D (GSDMD)-mediated pyroptosis in HN remains obscure. We found GSDMD was upregulated in the kidney tissue of HN mice, which was accompanied by the loss of renal function, renal tubular fibrosis, and reduced body weight. These changes in HN mice were inhibited by GSDMD knockout. Knockdown of GSDMD inhibited the high uric acid-induced injury in cultured cells (NRK-52E). Mechanistically, co-immunoprecipitation showed that RIG-I exist in a complex with caspase-1. Overexpression of RIG-I induced increased expression of caspase-1 protein and caspase-1 activity. Caspase-1 interference significantly reduced the increase of caspase-1 activity and IL-1ß production caused by RIG-I overexpression. Knockdown of RIG-I or caspase-1 decreased high uric acid-induced injury in NRK-52E. This work illustrates that targeting the RIG-I/caspase-1/GSDMD may provide potential therapeutic benefits to HN.
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PURPOSE: Glomerular mesangial cell (GMC) dysfunction plays a vital role in the pathogenesis of diabetic kidney disease (DKD). Transient receptor potential canonical 6 (TRPC6) has been demonstrated to be involved in the development of DKD. However, the underlying mechanism remains unclear. The present study investigated the role of TRPC6 in GMC dysfunction and the related mechanism. METHODS: Diabetic rats and cultured GMCs were used in the experiment. The diabetic rat model was created by intraperitoneal injection of streptozotocin. Protein and mRNA levels were assessed by Western blotting and quantitative RT-PCR, respectively. Histological changes in the kidneys were observed by immunochemistry and hematoxylin and eosin. TRPC6 knockdown was achieved by adenovirus-mediated TRPC6 shRNA delivery in vivo and TRPC6 siRNA transfection in vitro. RESULTS: TRPC6 expression was increased in diabetic rat kidneys. Knockdown of TRPC6 attenuated diabetes-induced kidney functional deterioration. In addition, the increases in extracellular matrix components, including collagen IV, collagen I, and fibronectin production, as well as NFAT2 expression were also suppressed. In cultured GMCs, high glucose (25 mM, HG) treatment increased the expression of TRPC6. Knockdown of TRPC6 alleviated HG-induced increases in collagen IV, fibronectin, and NFAT2 expression. Knockdown of NFAT2 also inhibited the upregulation of proteins, including collagen IV and fibronectin, in HG-treated GMCs. CONCLUSION: These results demonstrate that inhibition of TRPC6/NFAT2 signaling attenuates GMC dysfunction and the development of DKD and suggest that pharmacological targeting of TRPC6/NFAT2 in GMCs may provide beneficial effects for DKD.
Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Ratos , Animais , Células Mesangiais , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Fibronectinas/metabolismo , Canal de Cátion TRPC6/genética , Canal de Cátion TRPC6/metabolismo , RNA Interferente Pequeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Estreptozocina , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Linfócitos T , Glucose/metabolismo , RNA Mensageiro/metabolismo , Colágeno/metabolismo , Células CultivadasRESUMO
The protective effects of antibiotics against infection in cancer patients treated with chemotherapy remains unclear and related studies have been performed in healthy or pathogen-infected animal models. Here, we aimed to study the effects of antibiotic use on intestinal infection in tumor-bearing mice treated with chemotherapy and to determine the underlying mechanisms. Subcutaneous CT26 tumor-bearing mice were assigned to four groups: the control (Ctrl) group without any treatment, the antibiotic (ATB) group treated with a mixture of ampicillin, streptomycin, and colistin, the 5-fluorouracil (FU) group treated with four cycles of intraperitoneal injections of FU, and the ATB + FU group treated with the combination of ATB and FU. Gut microbial composition was determined and mesenteric lymph nodes (mLNs) were isolated for bacterial culturing. Intestinal permeability and integrity were assessed and the expression of cytokines was analyzed by quantitative PCR, ELISA, or flow cytometry (FCM). Monocytes in the colonic lamina propria (LP) were measured by FCM. Compared with the Ctrl and FU groups, the numbers of positive bacterial culturing results for mLNs were higher, and gut bacterial compositions were altered in the ATB and ATB + FU groups, with significantly decreased alpha diversity in the ATB + FU group. Intestinal integrity regarding the expression of tight junction proteins and intestinal permeability were not impaired significantly after treatments, but the colons were shorter in the ATB + FU group. The expression levels of intestinal IL-17A and IL-22, as well as the percentages of IL-17A+ cells in the colonic LP of the ATB + FU group, were lower than those in the FU group. The percentages of Ly6Chi monocytes in the colonic LP were lower, but those in the spleen were higher in the ATB + FU group than in the FU group. The mRNA levels of colonic CCL8 were reduced in the ATB + FU group. Antibiotic use is associated with an increased incidence of intestinal infections in tumor-bearing mice treated with chemotherapy, which might in turn be associated with a dysregulated gut microbiota that inhibits colonic monocyte recruitment and IL-17A and IL-22 production.
Assuntos
Microbioma Gastrointestinal , Neoplasias , Camundongos , Animais , Monócitos , Interleucina-17/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Mucosa Intestinal/metabolismo , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Fluoruracila/metabolismo , Neoplasias/metabolismo , Camundongos Endogâmicos C57BL , Interleucina 22RESUMO
Esophageal squamous cell carcinoma (ESCC) is notorious for the rapid progression especially early tumor metastasis due to the unclear mechanism. Recently, ETV5 attracts much attention for its potential role as an oncogenic transcription factor involved in multiple cancers. However, no one reported the mechanism behind the association between ETV5 expression and esophageal squamous cell carcinoma progression. In this study, we found that ETV5 was upregulated in ESCC both from online database and our ESCC tissues and ETV5 was associated with tumor staging and prognosis. Knockdown of ETV5 or its downstream genes SKA1 and TRPV2 significantly suppress ESCC cells migration and invasion, respectively. Additionally, in vivo study showed knockdown of ETV5 inhibited tumor metastasis. Further experiments unveiled ETV5 could transcriptionally upregulate the expression of SKA1 and TRPV2 and further activate MMPs in ESCC progression. In conclusion, ETV5 was associated with ESCC tumor staging and ESCC prognosis clinically. ETV5 promoted metastasis of ESCC by activating MMPs through augmenting the transcription of SKA1 and TRPV2. ETV5 was likely to be a novel oncogene and therapeutic target in ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , Prognóstico , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: Submucosal tunneling endoscopic resection (STER) is widely applied for treatment of gastrointestinal submucosal tumors (SMTs) originating from the muscularis propria layer. However, the tumor location within the proximal esophagus makes STER a challenge for the endoscopists. The aim of this study was to summarize the technique skill and evaluate the outcomes of proximal esophageal STER. STUDY DESIGN: A total of 72 patients with SMTs in the proximal esophagus undergoing STER were included from February 2019 to March 2021. Imaging 3-dimensional reconstruction was used for patients with large SMTs. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. RESULTS: In this study, all the tumors were removed completely and no gross disease was remaining. The en bloc resection was achieved in 90.28% of patients, and the complications rate was 6.95%. Three-dimensional reconstruction was used for 30 patients (41.67%) with large SMTs (transverse diameter >2.0 cm). Based on statistical analysis, tumors with irregular shape and larger size were the significant contributors to piecemeal resection. Larger tumors increase the risk of long operation time, and irregular tumor shapes increase the risk of complications. The median hospitalization time was 4 days. All of the complications were cured by conservative treatment. A median follow-up of 12 months was available, and all patients were free from local recurrence or distant metastasis during the study period. CONCLUSIONS: STER is an effective and safe methodology for the resection of proximal esophageal SMTs. Tumor size and shape mainly impact the piecemeal resection rate, STER-related complications, and procedural difficulty.
Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Neoplasias Gastrointestinais , Neoplasias Gástricas , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Mucosa Gástrica/patologia , Neoplasias Gastrointestinais/patologia , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
Our study aimed to determine the effects of pilocarpine and the mechanisms involving muscarinic acetylcholine receptors (mAChRs) on glycine receptors (GlyRs) in neurons of the spinal cord ventral horn. An enzymatic digestion combined with acute mechanical separation was applied to isolate neurons from the spinal cord ventral horn. Patch-clamp recording was then used to investigate the outcomes of pilocarpine. Our results indicate that pilocarpine increased the glycine currents in a concentration-dependent manner, which was blocked by the M3-AChR selective antagonists 4-DAMP and J104129. Pilocarpine also enhanced the glycine currents in nominally Ca2+-free extracellular solution. Conversely, the enhancement of glycine currents by pilocarpine disappeared when intracellular Ca2+ was chelated by BAPTA. Heparin and Xe-C, which are IP3 receptor antagonists, also totally abolished the pilocarpine effect. Furthermore, Bis-IV, a PKC inhibitor, eliminated the pilocarpine effect. Additionally, PMA, a PKC activator, mimicked the pilocarpine effect. These results indicate that pilocarpine may increase the glycine currents by activating the M3-AChRs and IP3/Ca2+/PKC pathways.
Assuntos
Células do Corno Anterior , Glicina , Células do Corno Anterior/metabolismo , Glicina/metabolismo , Glicina/farmacologia , Pilocarpina/farmacologia , Transdução de Sinais , Medula Espinal/metabolismoRESUMO
OBJECTIVES: To investigate why patients with terminal illness and their families in Shanghai choose the hospice ward and their decision-making process. METHODS: This was a mixed-method study consisting of a cross-sectional survey and a descriptive qualitative study. Medical decision-makers for patients hospitalized in hospice wards were recruited between September 2019 and July 2021. A medical decision-maker is a family member who makes medical decisions for a patient. All 146 participants completed a self-developed 10-item questionnaire that included five items about their demographic characteristics and five items about the decision-making process. The semi-structured interviews were conducted with nine participants to understand the family's decision-making process when they chose a hospice ward. The interviews were analyzed using qualitative content analysis. RESULTS: The mean age of the 146 participants was 57.6 years old. Of the decision-makers, 56.85% were the patients' children. Family-dominated discussions involving other family members were the main decision-making mode (84.93%). Patient participation in the decision-making process was reported in 43.15% of families. The participation of doctors (17.81%) and nurses (2.05%) were reported in a small number of families. The most common reason for choosing the hospice ward was the inability to find any other hospital for the patients (82.19%). The most common ways to learn about the service were neighbors and friends (38.36%) and social media (28.77%). Two themes and six categories emerged from the interviews. The first theme was reasons for choosing hospice wards. The reasons included being unable to care for the patients at home, staying in a hospice ward could reduce the psychological stress for home care, being unable to be admitted into tertiary/secondary hospitals, and thinking a hospice ward was a suitable place for the family. The second theme was the decision process of choosing a hospice ward. This theme included the following two categories, i.e., ways to learn about the hospice ward and family-discussion decision mode. CONCLUSION: To most families having dying patients, a hospice ward is a reasonable and balanced choice after the families experience huge care stress and practical difficulties. The participation of patients should be encouraged in the family discussion so that their wishes can be known. More efforts will be needed to guide the families with dying patients to make reasonable medical choices. Social media can be a good way to improve public awareness of hospice services in the future. Meanwhile, healthcare providers should be more involved in the decision-making process.
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BACKGROUND: Endoscopic submucosal dissection (ESD) of superficial squamous epithelial lesions at the pharynx is still a challenge for most endoscopists due to the limited working space and inexperience. The aim of this study was to evaluate the outcomes of ESD for superficial pharyngeal carcinomas. METHODS: A total of 30 superficial carcinomas at the pharynx in 27 consecutively treated patients were included. The rates of en bloc resection, complete resection, major complications, local recurrence, and metastasis were evaluated retrospectively as the therapeutic outcomes. RESULTS: The en bloc and complete resection rates were respectively 100% and 93.3%. No bleeding, perforation, or dyspnea during or after the ESD procedure occurred. There was 1 patient with emphysema. The median hospital stay was 6 days. During the follow-up period of 1 year, 1 patient had neck lymph node metastasis. CONCLUSION: ESD is effective and safe for resection of superficial carcinomas at the pharynx, with a high complete resection rate and favorable outcomes.