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Objectives: To evaluate the efficacy of miniprobe endoscopic ultrasonography for the diagnosis and adjuvant treatment of patients with colorectal submucosal lesions. METHODS: The retrospective study was conducted at the Beijing Chao-Yang Hospital, Capital Medical University, China, and comprised data from January 1, 2016, to July 31, 2021, related to patients of either gender with colorectal submucosal lesions who underwent miniprobe endoscopic ultrasonography. The findings were compared with biopsy specimens and clinical diagnoses. Diagnostic features of miniprobe endoscopic ultrasonography were assessed along with its accuracy. Data was analysed using R 4.1.2. RESULTS: Of the 237 patients, 121(51.1%) were female and 116(48.9%) were male. The overall mean age was 55.6±12.9 years. Miniprobe endoscopic ultrasonography successfully imaged all 237(100%) colorectal submucosal lesions, and 188(79.3%) had consistent results compared to histopathological findings. The majority of lesions were <10mm 102(43.4%) or 10-19mm 84(35.7%) in size. Those detected with high echogenicity were 126(53.2%) and those with low/low-medium echogenicity were 83(35.0%). Tumour size 10-19mm and uneven echo quality significantly increased the accuracy of miniprobe endoscopic ultrasonography (p<0.05). CONCLUSIONS: Miniprobe endoscopic ultrasonography was able to provide precise information about the size, layer of origin, echogenicity and border of colorectal submucosal lesions, and had a high accuracy in the differential diagnosis of such lesions.
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Neoplasias Colorretais , Endossonografia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Endossonografia/métodos , Estudos Retrospectivos , China , Diagnóstico Diferencial , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologiaRESUMO
BACKGROUND: Among all types of superficial gastrointestinal (GI) neoplasms, colorectal lesions are recognized as one of the most difficult locations to operate, due to the limited operation space, physiological bends, poor visualization of the submucosal dissection plane sheltered by colorectal crinkle wall, and the thin intestinal mucosa layer which is easy to perforation. The purpose of this prospective study is to evaluate the feasibility, efficacy, and safety of a novel endoscopic traction technique in assisting the endoscopic submucosal dissection (ESD) procedure in colorectal lesions. METHOD: A total of 117 patients with colonic lesions who underwent endoscopic treatment were enrolled between August 2020 and January 2021 at the endoscopic center of Beijing Chao-yang Hospital of Capital Medical University. Based on whether traction device was used during the operation, 60 and 57 patients were assigned to the conventional ESD group and clips and rubber band triangle traction-assisted ESD group (CRT-ESD, in which three clips and a rubber band were used to form an elastic triangular traction device), respectively. The total procedure time (TPT), submucosal dissection time (SDT), submucosal dissection speed (SDS), and rate of adverse events of the two groups were analyzed. RESULTS: After excluding patients who did not undergo treatment (conventional ESD, 1; CRT-ESD, 4), 112 patients were included in the study (conventional ESD, 59; CRT-ESD, 53). The baseline characteristics of the patients were well balanced between the two groups. The TPT (58.71 ± 26.22 min vs 33.58 ± 9.88 min, p < 0.001) and SDT (49.24 ± 23.75 min vs 26.34 ± 8.75 min, p < 0.001) were significantly different between the conventional ESD group and CRT-ESD group. The CRT-ESD group had significantly higher SDS than that of the traditional ESD group (0.54 ± 0.42 cm2/min vs 0.89 ± 0.40 cm2/min, p < 0.001). There were 4 (6.8%) cases of perforation in the traditional ESD group, and no perforation occurred in traction-assisted ESD. CONCLUSIONS: Compared with traditional ESD, CRT-ESD with clip and rubber band is both safer and more effective in the treatment of colorectal lesions.
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Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Neoplasias Gastrointestinais , Humanos , Ressecção Endoscópica de Mucosa/métodos , Tração , Estudos Prospectivos , Resultado do Tratamento , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologiaRESUMO
Glycosylation is a common posttranslational modification of proteins, which plays a role in the malignant transformation, growth, progression, chemoresistance, and immune response of tumors. Disulfide isomerase family A3 (PDIA3) specifically acts on newly synthesized glycoproteins to promote the correct folding of sugar chains. Studies have shown that PDIA3 participates in multidrug-resistant gastric cancer (MDR-GC). In this study, we performed western blot analysis and immunohistochemistry to identify PDIA3 expression. Cell proliferation was assessed by CCK-8 assay. Transwell assays were used to detect the migration and invasion abilities of cells. Immunoprecipitation coupled to mass spectrometry (IP-MS) analysis was employed to identify PDIA3-interacting proteins and the associated pathways in MDR-GC cells. Glycoprotein interactions and translocation were detected by immunofluorescence assay. The results showed that PDIA3 knockdown significantly inhibited the proliferation, invasion, and migration abilities of MDR-GC cells. Kyoto Encyclopedia of Genes and Genomes analysis of the IP-MS results showed that PDIA3 was closely associated with focal adhesion pathways in MDR-GC cells. Additionally, important components of focal adhesion pathways, including fibronectin-1 (FN1) and integrin α5 (ITGA5), were identified as pivotal PDIA3-binding glycoproteins. Knockdown of PDIA3 altered the cellular locations of FN1 and ITGA5, leading to abnormal accumulation. In conclusion, our results suggest that knockdown of PDIA3 inhibited the malignant behaviors of MDR-GC cells and influenced the translocation of FN1 and ITGA5.
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Proliferação de Células , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Retículo Endoplasmático/enzimologia , Inativação Gênica , Proteínas de Neoplasias/biossíntese , Isomerases de Dissulfetos de Proteínas/biossíntese , Neoplasias Gástricas/enzimologia , Linhagem Celular Tumoral , Retículo Endoplasmático/genética , Retículo Endoplasmático/patologia , Humanos , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Isomerases de Dissulfetos de Proteínas/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
Berberine (BBR), a natural isoquinoline alkaloid, has been shown to be a promising therapeutic agent for colorectal cancer (CRC), but the molecular mechanism remains unclear. Here, we used mass spectrometry-based label-free proteomics to explore the potential targets of BBR in CRC cells. Comprehensive proteomic profiles demonstrated that of 8051 identified proteins, 503 and 277 differentially expressed proteins (DEPs) were screened out of CACO2 and LOVO cells, respectively. 83 DEPs were overlapped and most of these were down-regulated. A pathway enrichment analysis pinpointed mitochondrial translation, respiratory electron transport and the citric acid (TCA) cycle as biological effectors. The data of proteomics was subsequently confirmed by citrate synthase (CS), Tu translation elongation factor (TUFM), pentatricopeptide repeat domain 3 (PTCD3) and mitochondrial ribosomal protein L48 (MRPL 48) protein measurement. CS protein expression in CRC cells and tissues was higher than it was in normal specimens. Additionally, forcible downregulation of CS led to remarkable cell proliferation inhibition. Taken together, we concluded that the anticancer effects of BBR are attributable to mitochondrial protein synthesis, TCA and respiratory electron transport inhibition and that CS might be a useful therapeutic target in CRC treatment.
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BACKGROUND: The Asia-Pacific Colorectal Screening (APCS) score is effective to screen high-risk groups of advanced colorectal neoplasia (ACN) patients but needs revising and can be combined with the fecal immunochemical test (FIT). This paper aimed to improve the APCS score and evaluate its use with the FIT in stratifying the risk of ACN. METHODS: This prospective and multicenter study enrolled 955 and 1201 asymptomatic Chinese participants to form the derivation and validation set, respectively. Participants received the risk factor questionnaire, colonoscopy and FIT. Multiple logistic regression was applied, and C-statistic, sensitivity and negative predictive values (NPVs) were used to compare the screening efficiency. RESULTS: A modified model was developed incorporating age, body mass index (BMI), family history, diabetes, smoking and drinking as risk factors, stratifying subjects into average risk (AR) or high risk (HR). In the validation set, the HR tier group had a 3.4-fold (95% CI 1.8-6.4) increased risk for ACN. The C-statistic for the modified score was 0.69 ± 0.04, and 0.67 ± 0.04 for the original score. The sensitivity of the modified APCS score combined with FIT for screening ACN high-risk cohorts was 76.7% compared with 36.7% of FIT alone and 70.0% of the modified APCS score alone. The NPVs of the modified score combined with FIT for ACN were 98.0% compared with 97.0% of FIT alone and 97.9% of the modified APCS score alone. CONCLUSIONS: The modified score and its use with the FIT are efficient in selecting the HR group from a Chinese asymptomatic population.
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Colonoscopia , Neoplasias Colorretais/diagnóstico , Sangue Oculto , Fatores Etários , Consumo de Bebidas Alcoólicas , Doenças Assintomáticas , China , Neoplasias Colorretais/patologia , Diabetes Mellitus , Exercício Físico , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade , Valor Preditivo dos Testes , Estudos Prospectivos , Análise de Regressão , Medição de Risco , Fatores de Risco , Tamanho da Amostra , Sensibilidade e Especificidade , Fatores Sexuais , Fumar , Inquéritos e QuestionáriosRESUMO
Pancreatic stellate cells (PSCs), when activated, are characterized by proliferation and collagen synthesis, and contribute to extracellular matrix deposition in pancreatic fibrosis. Concomitantly, fibrosis is linked with the loss of PTEN (phosphatase and tensin homolog) protein in several organs. This study investigated the association between PTEN protein levels and the activated or apoptotic status of PSCs in a rat model of chronic pancreatitis. In addition, the activation status and biological behaviors of culture-activated PSCs were analyzed after lentiviral transfection with wildtype or mutant (G129E) PTEN for upregulation, or PTEN short hairpin RNA for downregulation, of PTEN. In vivo, PTEN levels gradually decreased during pancreatic fibrosis, which positively correlated with apoptosis of activated PSCs, but negatively with PSC activation. In vitro, activated PSCs with wildtype PTEN showed less proliferation, migration, and collagen synthesis compared with control PSCs, and greater numbers were apoptotic; activated PSCs with mutant PTEN showed similar, but weaker, effects. Furthermore, AKT and FAK/ERK signaling was involved in this process. In summary, activated PSCs during pancreatic fibrosis in vivo have lower levels of PTEN. In vitro, PTEN appears to prevent PSCs from further activation and promotes apoptosis through regulation of the AKT and FAK/ERK pathways.
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PTEN Fosfo-Hidrolase/metabolismo , Pâncreas/patologia , Células Estreladas do Pâncreas/enzimologia , Animais , Apoptose , Movimento Celular , Proliferação de Células , Células Cultivadas , Colágeno/metabolismo , Fibrose , Humanos , Masculino , Pâncreas/enzimologia , Células Estreladas do Pâncreas/citologia , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/fisiologia , Ratos Wistar , Transdução de SinaisRESUMO
Tobacco smoking is an independent risk factor for the initiation of pancreatic cancer (PC). Hypermethylation of tumor suppressor genes has been demonstrated to be associated with smoking. This study aimed to find the relationship between nicotine exposure and hypermethylation of tumor suppressor genes in normal pancreatic epithelial cells. Human pancreatic epithelial cells ware cultured exposing to nicotine and the methylation status of tumor suppressor genes were detected. Proenkephalin (PENK) was chosen as the target gene and methylation level of PENK promoter region was measured. Expression of DNA methyltransferase (DNMT), nicotine acetylcholine receptor (α7nAChR) and signaling pathway downstream were analyzed. Nicotine induces overexpression of DNMT3A and 3B, and methylated-inactivation of PENK gene in normal pancreatic epithelial cells. An activation of α7nAChR and MAPK signaling pathway has been detected in the nicotine-treated group. Demethylated drug, antagonist of α7nAChR and inhibitor of p38 MAPK is verified to attenuate the overexpression of DNMTs stimulated by nicotine as well as inhibit aberrant hypermethylation-related silence of PENK gene. Nicotine stimulation can induce aberrant hypermethylation of tumor suppressor genes by α7nAChR and MAPK signaling pathway-mediated up-regulation of DNMTs in pancreatic epithelial cells, thus we can provide epigenetic evidence of the mechanisms by which smoking causes pancreatic cancer and find new therapeutic target.
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Metilação de DNA/genética , Células Epiteliais/metabolismo , Genes Supressores de Tumor , Nicotina/farmacologia , Ductos Pancreáticos/citologia , Apoptose/efeitos dos fármacos , Azacitidina/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Células Epiteliais/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mecamilamina/farmacologia , Metiltransferases/metabolismo , Nicotina/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Receptor Nicotínico de Acetilcolina alfa7/genéticaRESUMO
OBJECTIVES: Adenoma detection rate (ADR) is a key colonoscopy quality indicator in Western clinical literature. Our low ADR prompted us to assess novel methods to improve performance. Western retrospective reports suggested that water exchange (WE) could increase ADR. However, most of these studies used pain score or intubation rate as the primary outcome. Here we test the hypothesis that WE significantly increases ADR among Chinese colonoscopists and design a prospective randomized controlled trial using ADR as our primary outcome. METHODS: This prospective, randomized controlled trial was performed at six centers in China. Screening, surveillance, and diagnostic cases were randomized to be examined by WE or traditional air insufflation (AI) method. The primary outcome was ADR. RESULTS: From April 2014 to July 2015, 3,303 patients were randomized to WE (n=1,653) and AI (n=1,650). The baseline characteristics were comparable. Overall ADR was 18.3% (WE) and 13.4% (AI) (relative risk 1.45, 95% confidential interval: 1.20-1.75, P<0.001). ADR in screening patients using AI was 25.8% (male) and 15.7% (female). ADR in screening patients aged >50 years old was 29.4% (WE) and 22.9% (AI) (relative risk 1.09, 95% confidential interval: 1.00-1.19, P=0.040). The increase by WE was reproducibly observed in all indication categories, and significant in screening and diagnostic cases. The limitation imposed by the unblinded investigators was mitigated by comparable inspection times in cases without polyps, similar adenoma per positive colonoscopy, and reproducible enhancement of ADR and adenoma per colonoscopy by WE across all eight investigators. CONCLUSIONS: This prospective study confirms Western retrospective data that WE significantly improves ADR among Chinese colonoscopists. WE may be superior to AI for screening colonoscopy in China. Colonoscopists elsewhere with low ADR might consider evaluating WE for performance improvement.
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Adenoma/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Adulto , China , Colonoscopia/efeitos adversos , Detecção Precoce de Câncer , Feminino , Humanos , Insuflação , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Modelos de Riscos Proporcionais , ÁguaRESUMO
Objective To observe clinical efficacy of raw rhubarbs (by intranasal jejuna injection) for moderately severe acute pancreatitis (MSAP) , and its effects on gastrointestinal tract and coagulation fibrinolysis. Methods Totally 84 MSAP patients were randomly assigned to the control group and the treatment group by random number table, 42 in each group. All patients received routine medica- tion. Enteral nutrition by intranasal jejuna injection was input under the endoscope within 48 h of onset. Pa- tients in the treatment group additionally used raw rhubarbs (by intranasal jejuna injection) , 100 mL each time, twice per day, with the treatment duration for 3 -7 days. The recovery of gastrointestinal tract func- tion (passage of gas by anus, recovery time of bowel sound, distension disappearance time, abdominal pain disappearance time) was observed, prothrombin time (PT) , activated partial thromboplastin time (APTT), thrombin time (TT) , fibrinogen (Fib) content, platelet (PLT) count, D-dimer (DD), protein C were determined. Clinical efficacy was assessed as well. Results Compared with the control group, time for gas passage by anus, recovery time of bowel sound, distension disappearance time, and ab- dominal pain disappearance time were shortened, PT, APTT, Fib content, thrombin time, and DD decreased, and protein C increased in the treatment group (P <0. 05). The incidence rate of complications was lower in the treatment group than in the control group (P <0. 05). The cure rate was elevated (P < 0. 05). There was no statistical difference in the total effective rate between the two groups (P >0. 05). Conclusion Intranasal jejuna injection of raw rhubarbs in treating moderately severe acute pancreatitis could improve symptoms of gastrointestinal tract and coagulation fibrinolysis.
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Pancreatite , Tempo de Tromboplastina Parcial , Fitoterapia , Rheum , Administração Intranasal , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Humanos , Pancreatite/terapia , Fitoterapia/métodos , Tempo de ProtrombinaAssuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Doenças do Esôfago/diagnóstico , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Transtornos de Deglutição/etiologia , Diagnóstico Diferencial , Quimioterapia Combinada , Doenças do Esôfago/complicações , Doenças do Esôfago/tratamento farmacológico , Doenças do Esôfago/patologia , Esofagoscopia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Talidomida/administração & dosagem , Talidomida/uso terapêuticoRESUMO
BACKGROUND: Coagulopathy and its association with disease severity in hyperlipidemia (HL)- and non-hyperlipidemia (NHL)-induced acute pancreatitis (AP) are not clear. The present study was to evaluate the relationship between coagulation homeostasis and AP. METHODS: This study included 106 AP patients admitted to our hospital between October 2011 and January 2013. Stratified by disease severity, the patients were divided into two groups: a mild AP (MAP) group (n=69); and a moderately severe AP (MSAP) group (n=37). Based on disease etiology, there were 31 HL-induced AP (HLP) cases and 75 NHL-induced AP (NHLP) cases. The HLP and NHLP groups were compared for parameters of coagulation homeostasis, lipid metabolism, and disease severity. Correlations between disease severity and levels of D-dimer and protein C were investigated, and the prognostic potential of D-dimer was evaluated. RESULTS: Compared with MAP patients, MSAP patients showed higher levels of D-dimer and lower levels of protein C. HLP patients had higher protein C levels than NHLP patients. Both D-dimer and protein C levels were significantly associated with the disease severity, not the disease etiology. D-dimer levels correlated positively with low density lipoprotein cholesterol levels and performed well as a sensitive and specific predictor of disease severity in AP patients, especially in HLP patients. CONCLUSIONS: The coagulation homeostasis is different between HLP and NHLP patients, and HL may be a contributing factor for thrombosis and fibrinolysis in HLP. D-dimer may be a robust marker of disease severity in HLP.
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Coagulação Sanguínea , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hiperlipidemias/complicações , Pancreatite/etiologia , Doença Aguda , Adulto , Idoso , Biomarcadores/sangue , China , LDL-Colesterol/sangue , Feminino , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/diagnóstico , Masculino , Pessoa de Meia-Idade , Pancreatite/sangue , Pancreatite/diagnóstico , Valor Preditivo dos Testes , Proteína C/análise , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To explore the clinical efficacy and safety of compound digestive enzyme tablet in the treatment of dyspepsia. METHODS: A randomized, double-blind, double-dummy, positive drug parallel controlled, multicenter clinical trial was conducted for 203 dyspeptic patients from October 2011 to August 2012. And they were randomized into group A (experimental, n = 106) and group B (control, n = 97).Group A received 1 tablet of compound digestive enzyme tablet (Bearse) plus 2 analog capsules of compound digestive enzyme thrice daily. And group B had 2 capsules of compound digestive enzyme capsule (Dages) plus 1 analog tablet of compound digestive enzyme thrice daily. The total duration of drug treatment was 2 weeks. There were 3 follow-up visits (W0, W1, W2). The primary endpoint was the total effective rate of all dyspeptic symptoms. RESULTS: The total efficacy rate of groups A and B were 80.2% (85/106) and 79.4% (77/97) (P > 0.05). The adverse effects were 1.9% (2/106) and 4.1% (4/97) in groups A and B (P > 0.05). The adverse effects were mild in both groups. CONCLUSIONS: Compound digestive enzyme tablet and capsule are effective and safe for patients with dyspepsia. And compound digestive enzymes tablet is comparable to compound digestive enzyme capsule.
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Sistema Digestório , Cápsulas , China , Método Duplo-Cego , Fármacos Gastrointestinais , Humanos , Comprimidos , Resultado do TratamentoRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) is characterized by immune-mediated, chronic inflammation of the intestinal tract. The occurrence of IBD is driven by the complex interactions of multiple factors. The objective of this study was to evaluate the therapeutic effects of IAA in colitis. METHOD: C57/BL6 mice were administered 2.5% DSS in drinking water to induce colitis. IAA, Bifidobacterium pseudolongum, and R-equol were administered by oral gavage and fed a regular diet. The Disease Activity Index was used to evaluate disease activity. The degree of colitis was evaluated using histological morphology, RNA, and inflammation marker proteins. CD45+ CD4+ FOXP3+ Treg and CD45+ CD4+ IL17A+ Th17 cells were detected by flow cytometry. Analysis of the gut microbiome in fecal content was performed using 16S rRNA gene sequencing. Gut microbiome metabolites were analyzed using Untargeted Metabolomics. RESULT: In our study, we found IAA alleviates DSS-induced colitis in mice by altering the gut microbiome. The abundance of Bifidobacterium pseudolongum significantly increased in the IAA treatment group. Bifidobacterium pseudolongum ATCC25526 alleviates DSS-induced colitis by increasing the ratio of Foxp3+T cells in colon tissue. R-equol alleviates DSS-induced colitis by increasing Foxp3+T cells, which may be the mechanism by which ATCC25526 alleviates DSS-induced colitis in mice. CONCLUSION: Our study demonstrates that IAA, an indole derivative, alleviates DSS-induced colitis by promoting the production of Equol from Bifidobacterium pseudolongum, which provides new insights into gut homeostasis regulated by indole metabolites other than the classic AHR pathway.
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Bifidobacterium , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Camundongos , Animais , Equol/metabolismo , Equol/farmacologia , Equol/uso terapêutico , RNA Ribossômico 16S/genética , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Ácidos Indolacéticos/metabolismo , Doenças Inflamatórias Intestinais/patologia , Inflamação/patologia , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/farmacologia , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Colo/metabolismoRESUMO
Background: Ulcerative colitis (UC), which is characterized by chronic relapsing inflammation of the colon, results from a complex interaction of factors involving the host, environment, and microbiome. The present study aimed to investigate the gut microbial composition and metabolic variations in patients with UC and their spouses. Materials and Methods: Fecal samples were collected from 13 healthy spouses and couples with UC. 16S rRNA gene amplicon sequencing and metagenomics sequencing were used to analyze gut microbiota composition, pathways, gene expression, and enzyme activity, followed by the Kyoto Encyclopedia of Genes and Genomes. Results: We found that the microbiome diversity of couples with UC decreased, especially that of UC patients. Bacterial composition, such as Firmicutes, was altered between UC patients and healthy controls, but was not significantly different between UC patients and their spouses. This has also been observed in pathways, such as metabolism, genetic information processing, organismal systems, and human diseases. However, the genes and enzymes of spouses with UC were not significantly different from those of healthy individuals. Furthermore, the presence of Faecalibacterium correlated with oxidative phosphorylation, starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, and the bacterial secretion system, showed a marked decline in the UC group compared with their spouses, but did not vary between healthy couples. Conclusion: Our study revealed that cohabitation with UC patients decreased differences in the gut microbiome between healthy individuals and patients. Not only was the composition and diversity of the microbiota diminished, but active pathways also showed some decline. Furthermore, Firmicutes, Faecalibacterium, and the four related pathways may be associated with the pathological state of the host rather than with human behavior.
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Colite Ulcerativa , Microbioma Gastrointestinal , Microbiota , Humanos , Microbioma Gastrointestinal/genética , Colite Ulcerativa/genética , RNA Ribossômico 16S/genética , InflamaçãoRESUMO
Human chemokine receptor 8 (CCR8) is a promising drug target for immunotherapy of cancer and autoimmune diseases. Monoclonal antibody-based CCR8 targeted treatment shows significant inhibition in tumor growth. The inhibition of CCR8 results in the improvement of antitumor immunity and patient survival rates by regulating tumor-resident regulatory T cells. Recently monoclonal antibody drug development targeting CCR8 has become a research hotspot, which also promotes the advancement of antibody evaluation methods. Therefore, we constructed a novel engineered customized cell line HEK293-cAMP-biosensor-CCR8 combined with CCR8 and a cAMP-biosensor reporter. It can be used for the detection of anti-CCR8 antibody functions like specificity and biological activity, in addition to the detection of antibody-dependent cell-mediated cytotoxicity and antibody-dependent-cellular-phagocytosis. We obtained a new CCR8 mAb 22H9 and successfully verified its biological activities with HEK293-cAMP-biosensor-CCR8. Our reporter cell line has high sensitivity and specificity, and also offers a rapid kinetic detection platform for evaluating anti-CCR8 antibody functions.
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Anticorpos Monoclonais , Técnicas Biossensoriais , AMP Cíclico , Receptores CCR8 , Humanos , Células HEK293 , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Receptores CCR8/imunologia , Receptores CCR8/metabolismo , AMP Cíclico/metabolismo , Técnicas Biossensoriais/métodos , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Engenharia Celular/métodosRESUMO
INTRODUCTION: This study aimed to investigate the effects of nicotine on the activation of pancreatic stellate cells (PSCs) and pancreatic fibrosis in chronic pancreatitis (CP), along with its underlying molecular mechanisms. METHODS: This was an in vivo and in vitro study. In vitro, PSCs were cultured to study the effects of nicotine on their activation and oxidative stress. Transcriptome sequencing was performed to identify potential signaling pathways involved in nicotine action. And the impact of nicotine on mitochondrial Ca2+ levels and Ca2+ transport-related proteins in PSCs was analyzed. The changes in nicotine effects were observed after the knockdown of the mitochondrial calcium uniporter (MCU) in PSCs. In vivo experiments were conducted using a mouse model of CP to assess the effects of nicotine on pancreatic fibrosis and oxidative stress in mice. The alterations in nicotine effects were observed after treatment with the MCU inhibitor Ru360. RESULTS: In vitro experiments demonstrated that nicotine promoted PSCs activation, characterized by increased cell proliferation, elevated α-SMA and collagen expression. Nicotine also increased the production of reactive oxygen species (ROS) and cellular malondialdehyde (MDA), exacerbating oxidative stress damage. Transcriptome sequencing revealed that nicotine may exert its effects through the calcium signaling pathway, and it was verified that nicotine elevated mitochondrial Ca2+ levels and upregulated MCU expression. Knockdown of MCU reversed the effects of nicotine on mitochondrial calcium homeostasis, improved mitochondrial oxidative stress damage and structural dysfunction, thereby alleviating the activation of PSCs. In vivo validation experiments showed that nicotine significantly aggravated pancreatic fibrosis in CP mice, promoted PSCs activation, exacerbated pancreatic tissue oxidative stress, and increased MCU expression. However, treatment with Ru360 significantly mitigated these effects. CONCLUSIONS: This study confirms that nicotine upregulates the expression of MCU, leading to mitochondrial calcium overload and exacerbating oxidative stress in PSCs, and ultimately promoting PSCs activation and exacerbating pancreatic fibrosis in CP.
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BACKGROUND AND AIM: Recently, Gastroesophageal Reflux Disease Questionnaire (GerdQ) has been developed for diagnosis of GERD. However, no study investigated its value in real-world practice. This study aimed to investigate whether GerdQ can be used for diagnosis of GERD in China. METHODS: A national multicenter survey was undertaken; all patients who underwent first diagnostic upper endoscopy for upper gastrointestinal (GI) symptoms were included. Data including the gender, age, symptoms, and endoscopic findings were prospectively recorded. The GerdQ score was measured before endoscopic procedure. RESULTS: Totally, 8065 patients were included. One thousand four hundred and thirty-five patients (17.8%) had reflux esophagitis. Among them, 620 (43.2%) patients' GerdQ score was ≥ 8. For 2025 patients with GerdQ ≥ 8, 620 (30.6%) were found to have reflux esophagitis, but the remaining 69.4% (1405/2025) were normal. Proportions of patients with reflux esophagitis increased in cut-off range from 3-18 for GerdQ. However, 22.2% of the patients with a GerdQ score ≤ 2 also had reflux esophagitis. Twenty-eight (0.3%) patients were diagnosed to have upper GI malignancies, and 10 out of these 28 (35.7%) patients' GerdQ score was ≥ 8. CONCLUSIONS: The study suggests the proportions of Chinese patients with reflux esophagitis rise up with the increase of GerdQ score, and GerdQ may be used for diagnosis of GERD. However, low GerdQ score cannot exclude the possibility of reflux esophagitis. A minority of Chinese patients has high GerdQ score but is diagnosed with malignancies, even in the absence of alarm features.
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Refluxo Gastroesofágico/diagnóstico , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Autoavaliação Diagnóstica , Endoscopia Gastrointestinal , Esofagite Péptica/complicações , Feminino , Refluxo Gastroesofágico/etiologia , Neoplasias Gastrointestinais/complicações , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemAssuntos
Infarto do Baço/complicações , Acidente Vascular Cerebral/etiologia , Trombocitemia Essencial/complicações , Isquemia Encefálica/etiologia , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Infarto do Baço/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Trombocitemia Essencial/diagnóstico por imagemRESUMO
Background: Colorectal cancer (CRC) is the third most common cancer in the world and has a high mortality rate. Colorectal adenoma (CRA) is precancerous lesions of CRC. The purpose of the present study was to construct a nomogram predictive model for CRA with low-grade intraepithelial neoplasia (LGIN) in order to identify high-risk individuals, facilitating early diagnosis and treatment, and ultimately reducing the incidence of CRC. Methods: We conducted a single-center case-control study. Based on the results of colonoscopy and pathology, 320 participants were divided into the CRA group and the control group, the demographic and laboratory test data were collected. A development cohort (n = 223) was used for identifying the risk factors for CRA with LGIN and to develop a predictive model, followed by an internal validation. An independent validation cohort (n = 97) was used for external validation. Receiver operating characteristic curve, calibration plot and decision curve analysis were used to evaluate discrimination ability, accuracy and clinical practicability of the model. Results: Four predictors, namely sex, age, albumin and monocyte count, were included in the predictive model. In the development cohort, internal validation and external validation cohort, the area under the curve (AUC) of this risk predictive model were 0.946 (95%CI: 0.919-0.973), 0.909 (95 % CI: 0.869-0.940) and 0.928 (95%CI: 0.876-0.980), respectively, which demonstrated the model had a good discrimination ability. The calibration plots showed a good agreement and the decision curve analysis (DCA) suggested the predictive model had a high clinical net benefit. Conclusion: The nomogram model exhibited good performance in predicting CRA with LGIN, which can aid in the early detection of high-risk patients, improve early treatment, and ultimately reduce the incidence of CRC.
RESUMO
OBJECTIVE: To investigate the therapeutic value of self-expanding metallic stent (SEMS) for resectable obstructing left-sided colon cancer or rectal cancer. METHODS: Clinical data of 73 patients who had acute obstruction due to left-sided colon cancer or rectal cancer during May 2007 to January 2012 were retrospectively analyzed. The patients were divided into 2 groups: SEMS group (34 cases) underwent surgical resection after insertion of SEMS; emergency surgery group (39 cases) underwent emergency operation. The 2 group patients were compared for the incidence of primary anastomosis, stoma rate, laparoscopic surgery rate, mortality, postoperative morbidity, ICU admission rate, length of ICU stay, hospital stay, and hospitalization costs. RESULTS: The incidence of primary anastomosis in SEMS group was significantly higher than that in emergency surgery group (97.1% vs. 56.4%, χ(2) = 16.256, P < 0.001), and the protective stoma rate and permanent stoma rate in SEMS group were both lower than those in emergency surgery group (33.3% vs. 86.3%, 2.9% vs. 43.6%, χ(2) value were 14.972 and 16.156, both P < 0.001). Patients in SEMS group underwent significantly more laparoscopic surgery than in emergency surgery group (47.1% vs. 0, χ(2) = 23.505, P < 0.001). There were no significant difference in postoperative mortality (2.9% vs. 10.3%, P = 0.364). The postoperative morbidity in SEMS group was significantly lower than that in emergency surgery group (35.3% vs. 66.7%, P = 0.007). Incisional infection was the most common complication in both groups, and the incidence of which seemed to be more higher in emergency surgery group (17.6% vs. 38.5%, χ(2) = 3.840, P = 0.050). There was a lower ICU admission rate in SEMS group (24.2% vs. 53.9%, χ(2) = 6.972, P = 0.008), and the mean length of ICU stay and hospital stay were both shorter in SEMS group ((69.5 ± 7.4) hours vs. (114.3 ± 10.9) hours, t = -20.23, P < 0.001; (19.6 ± 4.8) days vs. (23.4 ± 6.2) days, t = -2.90, P = 0.005). The cost of hospitalization was less in SEMS group (45 383 ± 15 648 vs. 61 485 ± 20 380, t = -3.74, P < 0.001). CONCLUSIONS: SEMS can effectively relieve the large intestinal obstruction caused by left-sided colon cancer or rectal cancer, and change the traditional emergency surgery into a selective surgery with better outcomes. SEMS appears to be a valuable technique for resectable obstructing left-sided colorectal cancer.