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Estrogens and their metabolites (EMs) are involved in chronic liver disease and gut microbiota regulates estrogen metabolism, whereas the role of enterogenous EMs in liver disease is still elusive. Because of the extremely low level of EMs in portal serum and the EMs contain multiple pairs of isomers, an accurate determination of portal serum EMs is urgently needed. This study established a quantitative detection method for portal serum EMs and applied to non-alcoholic fatty liver disease (NAFLD) related hepatic fibrosis mice model. The serum was derived with a novel derivatization reagent 4-acetyl aminobenzene sulfonyl chloride, and a UPLC-ESI-MS system was used for quantification of 15 EMs in 120 min. Compared with normal group, the concentrations of E1, E2 in model group were significantly decreased by 4-8 times, all the C2 and C4 substitution products (2-OHE1, 2-OHE2, 2-MeOE1, 4-OHE1, 4-MeOE1, 4-OHE2, 4-MeOE2, 2-MeOE2) were significantly decreased by 2-22 times. However, the C16 and C17 substitution products (E3, 16-epiE3, 17-epiE3, 16-ketoE2) levels were increased by 3-5 times (P < 0.01). This study elucidated the changes of enterogenous EMs which entered the liver via portal vein in NAFLD - related hepatic fibrosis and provided methodological platform for other related studies on estrogen metabolism.
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Estrogênios , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Cirrose HepáticaRESUMO
BACKGROUND: Fecal DNA and occult blood testing have been gradually developed for colorectal cancer (CRC) screening. Comparison of different testing strategies for these methods in CRC screening is in urgent need. This study aims to examine the efficacy of different testing strategies including multi-target fecal DNA testing, qualitative and quantitative fecal immunoassay tests (FITs). METHODS: Fecal samples were collected from patients diagnosed by colonoscopy. Tests using fecal DNA, quantitative FIT or qualitative FIT were performed on same fecal samples. Efficiency of different testing strategies within different populations was investigated. RESULTS: For high-risk populations (CRC and advanced adenoma), the positive rate of the three methods alone was 74.3-80%; the positive predictive values (PPVs) ranged from 37.3% to 77.8%, and the negative predictive values (NPVs) ranged from 86.3% to 92.2%. For combined testing strategies, the positive rate was 71.4-88.6%, PPVs ranged from 38.3% to 86.2%, and NPVs ranged from 89.6% to 92.9%. Parallel fecal multi-target DNA test and quantitative FIT appears to be superior when using a combined testing strategy. For the normal population, no significant difference was identified in efficacy between these methods when used alone and in combination. CONCLUSIONS: Single testing strategy among the three methods is more suitable for the general population screening, and the combined testing strategy is more suitable for high-risk populations screening. The use of different combination strategies may have superiority in CRC high-risk population screening, but cannot conclude significant differences which may be attributed to the small sample size, large samples controlled trials are needed.
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Neoplasias Colorretais , Programas de Rastreamento , Humanos , Programas de Rastreamento/métodos , Sangue Oculto , Detecção Precoce de Câncer/métodos , Neoplasias Colorretais/diagnóstico , DNARESUMO
BACKGROUND: Postoperative fistula is a life-threatening complication that lacks a standard treatment strategy after laparoscopic sleeve gastrectomy (LSG). This observational study is the first to report the efficacy and safety of endoscopic full-thickness resection (EFTR) combined with purse-string sutures in treating this complication. PATIENTS AND METHODS: The old fistula was resected by EFTR, cut radially, and then sutured with a purse-string. The primary endpoint was complete fistula closure within two months. Endoscopic procedure-related complications were also recorded. RESULTS: Eight of 788 LSG patients developed fistulas with an incidence of 1.01%, primarily under the gastroesophageal junction, and the average distance from the center of the fistula to the cardia was 30 ± 6.3 mm. Two patients were cured by conservative treatment, and six received endoscopic sutures. The time from LSG to fistula diagnosis was 12.3 ± 14.4 days. The time from fistula diagnosis to endoscopic repair was 43.8 ± 55.8 days and 21.4 ± 10.0 days after eliminating the data of first case. The average fistula size was 12 ± 10 mm, the average endoscopic procedure duration was 40 ± 16 min, and the average number of endoscopic procedures required was 1.6 ± 0.8. Five patients achieved the primary endpoint, and one patient refused a third endoscopic suture after two sutures. The endoscopy success rate was 83.3%. No endoscopic procedure-related complications occurred. CONCLUSIONS: EFTR combined with purse-string sutures is an innovative, safe, and effective endoscopic strategy for postoperative fistula after LSG, avoiding reoperation and allowing early oral feeding.
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Fístula Gástrica , Laparoscopia , Obesidade Mórbida , Endoscopia Gastrointestinal/efeitos adversos , Gastrectomia/efeitos adversos , Fístula Gástrica/etiologia , Fístula Gástrica/cirurgia , Humanos , Laparoscopia/efeitos adversos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC). RESULTS: Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were randomized to the FMT group (n = 10) and the control group (n = 10); 80% were females (F/M = 16/4), the mean age was 48 ± 14 years, and the mean duration was 6.4 ± 8.2 years. The mean length of post-FMT follow-up was 19.1 ± 10.1 months (6-38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n = 10) when reassessed at week 4 (P = 0.001) and week 8 (P = 0.019) after FMT; there was no significant difference 6 months after treatment. The median remission time was 24 months (95% CI 68.26-131.7%) in both the FMT (range 6-38 months) and control groups (range 7-35 months), with no significant difference (P = 0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2 weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation. CONCLUSIONS: Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recurrent UC or even primary UC.
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Colite Ulcerativa/terapia , Transplante de Microbiota Fecal/métodos , Fezes/microbiologia , Microbioma Gastrointestinal/fisiologia , Adulto , Colite Ulcerativa/microbiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China. RESULTS: The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time. CONCLUSIONS: DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT.
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Seleção do Doador/métodos , Transplante de Microbiota Fecal/métodos , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Metagenômica/métodos , Doadores de Tecidos , Adolescente , Adulto , China , Infecções por Clostridium/terapia , Biologia Computacional/métodos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The goal of the present study was to investigate the effects of TAK-242 on the gut microbiota and the TLR4/JAK2/STAT3 signaling pathway in mice with dextran sulfate sodium (DSS)-induced colitis. RESULTS: At the phylum level, Bacteroidetes, Firmicutes, Actinobacteria, Cyanobacteria, Epsilonbacteraeota and Proteobacteria were the primary microbiota in the five groups. TAK-242 treatment significantly enhanced Verrucomicrobia and Actinobacteria; significantly decreased Cyanobacteria, Epsilonbacteraeota and Proteobacteria; and particularly promoted the growth of Akkermansia. TAK-242 markedly alleviated DSS-induced colitis symptoms and colonic lesions by promoting IL-10 release, inhibiting IL-17 release, downregulating TLR4 and JAK2/STAT3 mRNA and protein expression and increasing JAK2/STAT3 phosphorylation. CONCLUSION: TAK-242 modulates the structure of the gut microbiota in colitis and may be a novel therapeutic candidate for ulcerative colitis.
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Bactérias/efeitos dos fármacos , Colite/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Sulfonamidas/administração & dosagem , Animais , Bactérias/classificação , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Colo/microbiologia , Citocinas/imunologia , Sulfato de Dextrana , Fezes/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Receptor 4 Toll-Like/metabolismoRESUMO
BACKGROUND: Intestinal fibrosis is the major complication of Crohn's disease (CD). There are no other good treatments for CD except surgery and remains a refractory disease. Calycosin (CA), the active component of astragalus membranaceus, has been reported the potential effect on lung fibrosis and renal fibrosis. In this study, we aim to explore the effect of CA on intestinal fibrosis in vitro and the possible signal pathway. METHODS: The antifibrotic effect of CA is investigated in human intestinal fibroblasts (CCD-18Co) cells induced by transforming growth factor-ß1 (TGF-ß1). MTT method was used to screen the concentration of CA. Real-time polymerase chain reaction and western blot analysis were used to evaluate the expression of α-smooth muscle actin (α-SMA), collagen I, and TGF-ß/Smad pathway. RESULTS: The results showed that the concentration of CA was 12.5, 25, 50 µmol/L. CA could inhibit the expression of α-SMA and collagen I. In addition, CA regulated the expression of TGF-ß/Smad signaling pathway. CONCLUSION: This study demonstrated that CA could inhibit the activation of CCD-18Co cells and reduce the expression of extracellular matrix. Our study highlighted that CA-inhibited TGF-ß/Smad pathway through inhibiting the expression of p-Smad2, p-Smad3, Smad4, and TGF-ß1 and raised the Smad7 expression. Therefore, CA might inhibit intestinal fibrosis by inhibiting the TGF-ß/Smad pathway.
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AIMS: No consensus regarding the optimal endoscopic resection approach for rectal neuroendocrine tumors (R-NETs) measuring 10-20 mm, this study aims to investigate this issue. METHODS: Patients with R-NETs underwent either endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). The primary endpoint was the complete resection rate, and the secondary endpoints were surgery-related complications and long-term outcomes. RESULTS: 96 patients met the inclusion criteria, 84 patients completed endoscopic resection, and 5 patients were excluded. 79 patients were enrolled and divided into EMR (n = 21) and ESD groups (n = 58). 100% of ESD excisions reached the primary endpoint, while 90.5% of EMR. Endoscopic submucosal dissection can achieve higher R0 rate and lower positive margin rate than EMR. The mean operative time of ESD and EMR was 35.22 ± 8.96 min and 13.14 ± 3.26 min, respectively. The complication rates of ESD and EMR were 3.4% and 4.8%, respectively. For R-NETs between 10 mm and 20 mm, the R0 rate of ESD was significantly higher than that of EMR (100% vs 71.4%, P = .01) and the margin positive rate of ESD was significant lower than that of EMR (4.8% vs 42.9%, P < .05). Both ESD and EMR obtained 100% R0 resection of less than 10 mm R-NET. The median follow-up was 13 months (3-84 months); 1 patient relapsed 25 months after EMR and was re-treated with ESD. CONCLUSION: For R-NETs with a diameter less than 10 mm, both EMR and ESD were safe and effective and EMR is convenient and fast, with advantages. ESD offers superiority for R-NETs between 10 and 20 mm and can be considered as the preferred method.
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Ressecção Endoscópica de Mucosa , Tumores Neuroendócrinos , Neoplasias Retais , Humanos , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Duração da Cirurgia , Adulto , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Margens de ExcisãoRESUMO
Ovarian Brenner tumor with abnormally increased serum carbohydrate antigen 19-9 (CA19-9) level is extremely rare. A 70-year-old woman with abnormally elevated serum CA199 (1289 U/ml) found in routine physical examination. Pelvic CT and MRI scan revealed a large mass with large patches of calcification in the right adnexal area, and the patient achieved total hysterectomy and bilateral adnexectomy. Grossly, the right ovary had a solid enlargement of about 7.0 cm × 6.0 cm × 5.0 cm with irregular nodules and smooth surface and the cut surface of the mass showed that the tumor is cystic and solid. Microscopically, the tumor showed a background of fibrous tissue hyperplasia with nested and adenoid cell clusters with uniform cell size and clear boundaries. The cells were translucent with eosinophilic cytoplasm and calcification. Immunohistochemical staining showed CK7, CA125, and P63 presented diffusely strongly positive staining, while negativity for CK20, GATA3, AR, P53, and CgA. Ki-67 showed weak positive staining, about 1%. The serum CA199 level decreased significantly on the 5th day after surgery. Postoperative pathology and immunohistochemistry confirmed borderline Brenner tumor. This is the first to report a case of borderline Brenner tumor with an abnormally high serum level of CA199 before surgery. In clinical practice, the possibility of ovarian Brenner tumor should be considered when abnormal elevation of serum CA199 level cannot be reasonably explained.
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Tumor de Brenner , Neoplasias Ovarianas , Feminino , Humanos , Idoso , Tumor de Brenner/diagnóstico , Tumor de Brenner/cirurgia , Tumor de Brenner/patologia , Neoplasias Ovarianas/cirurgia , Biomarcadores Tumorais , CarboidratosRESUMO
Purpose: This study aimed to compare the changes in the expression of microRNA Let-7i in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and the correlation between Let-7i and innate pro-inflammatory factors. It is necessary to search for a new biomarker to guide the prognosis of AS. Methods: A total of 10 patients with AS and 10 healthy volunteers were selected as AS and control groups, respectively. The expression levels of Let-7i, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and interferon-gamma (IFN-γ) in PBMCs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) to explore the relationship between Let-7i and pro-inflammatory factors. Furthermore, the relationship between Let-7i and TLR4 was determined by the luciferase reporter technology. Results: The expression level of Let-7i in PBMCs of patients with AS was significantly lower than that of healthy control. The expression levels of TLR4, NF-κB, and IFN-γ in PBMCs derived from patients with AS were significantly higher than those of healthy control. The results show that Let-7i manipulation can regulate lipopolysaccharide (LPS)-induced TLR4 and IFN-γ expression in CD4+ T cells of patients with AS. The overexpression of Let-7i in T cells of patients with AS can suppress TLR4 and IFN-γ LPS-induced expression levels of cellular mRNA and protein. Let-7i can directly interfere TLR4-3'untranslated region (UTR) sequence and regulate the expression of the TLR4 gene in Jurkat T cells. Conclusion: Let-7i may be involved in the pathogenesis of AS, and Let-7i expression in PBMCs may be helpful for the diagnosis and treatment of AS in the future.
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BACKGROUND: There is no consensus on the number of ligation bands for varying grades of internal hemorrhoids (IH) in a single session of endoscopic rubber band ligation (ERBL). AIMS: The aims of this study were to investigate this issue. METHODS: Patients with IH were treated with ERBL. The primary endpoint was no hemorrhoid symptoms 6 weeks after ERBL. The secondary endpoints were postoperative complications and recurrence. RESULTS: One hundred twenty-three eligible patients met the inclusion criteria, and 3 patients were excluded. The average bands were 3.9 ± 1.1, and grade II hemorrhoids required significantly fewer bands than grade III hemorrhoids (3.45 ± 0.85 vs 4.35 ± 1.06, P = 0.000). 78.8% of patients achieved the primary endpoint. The efficacy of grade II hemorrhoids was higher than that of grade III hemorrhoids (87.8% vs 69.2%). The incidence of postoperative complications was not significantly correlated with the grade of hemorrhoids (P = 0.201) and the number of bands (P = 0.886). The median follow-up time was 14.3 ± 7.9 (1.3-30.9) months. The overall recurrence rate was 25.0%, with grade III significantly higher than grade I-II (32.8% vs 14.6%, P = 0.027). For grade III hemorrhoids, the recurrence rate was lower with more than 4 bands of ligation than with less than 4 bands (26.5% vs 53.3%). CONCLUSIONS: The average ERBL treatment of IH requires nearly four bands, and grade II hemorrhoids require less banding than grade III hemorrhoids, while the efficacy was better. Increasing the number of bands improves the treatment efficacy for grade III IH, which could be a strategy to reduce the recurrence rate without increasing postoperative complications.
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Hemorroidas , Humanos , Hemorroidas/cirurgia , Hemorroidas/complicações , Endoscopia , Resultado do Tratamento , Ligadura/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
Objective: To assess the efficacy and safety of fecal microbiota transplantation (FMT) for adult chronic insomnia. Methods: Patients treated with FMT for chronic diseases were divided into chronic insomnia and non-insomnia group. The primary endpoint was the efficacy of FMT for insomnia 4 weeks after treatment, the secondary endpoints included the impacts of FMT on anxiety, depression, health-related quality of life, gut microbiota, and adverse events associated with FMT. Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) were utilized to assess the efficacy of FMT on insomnia, self-rating anxiety/depression scale [Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS)] was employed to evaluate anxiety and depression. Quality of life was evaluated by SF-36. 16S rRNA sequencing was employed to analyze the gut microbiota and correlation analysis was performed. Results: Forty patients met the inclusion criteria and seven were excluded. 33 patients were enrolled and stratified into chronic insomnia group (N = 17) and non-insomnia group (N = 16). Compared to baseline, FMT significantly ameliorated the ISI (17.31 ± 5.12 vs. 5.38 ± 5.99), PSQI (14.56 ± 2.13 vs. 6.63 ± 4.67), SAS (54.25 ± 8.90 vs. 43.68 ± 10.64) and SDS (57.43 ± 10.96 vs. 50.68 ± 15.27) score and quality of life of chronic insomnia patients. 76.47% (13/17) of insomnia patients achieved the primary endpoints. In chronic insomnia patients, the relative abundance of Eggerthella marked enhanced at baseline, while the relative abundance of Lactobacillus, Bifidobacterium, Turicibacter, Anaerostipes, and Eisenbergiella significantly increased after FMT treatment, the latter positive correlated with the efficacy of FMT. Encouragingly, FMT also improved the sleep quality of non-insomnia patients. Conclusion: Eggerthella may potentially serve as a distinctive genus associated with chronic insomnia. FMT maybe a novel treatment option for adults with chronic insomnia and provide an alternative to traditional treatments for insomnia. The effects were positive correlated with the augmentation of probiotics, such as Bifidobacterium, Lactobacillus, Turicibacter, and Fusobacterium.
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BACKGROUND: Endoscopy plays an important role in the management of acute variceal bleeding (AVB) in patients with cirrhosis. This study aimed at determining the optimal endoscopy timing for cirrhotic AVB. METHODS: Patients with cirrhosis with AVB across 34 university hospitals in 30 cities from February 2013 to May 2020 who underwent endoscopy within 24 hours were included in this study. Patients were divided into an urgent endoscopy group (endoscopy <6 h after admission) and an early endoscopy group (endoscopy 6-24 h after admission). Multivariable analysis was performed to identify risk factors for treatment failure. Primary outcome was the incidence of 5-day treatment failure. Secondary outcomes included in-hospital mortality, need for intensive care unit, and length of hospital stay. A propensity score matching analysis was performed. In addition, we performed an analysis, in which we compared the 5-day treatment failure incidence and the in-hospital mortality among patients with endoscopy performed at <12 hours and 12-24 hours. RESULTS: A total of 3319 patients were enrolled: 2383 in the urgent endoscopy group and 936 in the early endoscopy group. After propensity score matching, on multivariable analysis, Child-Pugh class was identified as an independent risk factor for 5-day treatment failure (HR, 1.61; 95% CI: 1.09-2.37). The incidence of 5-day treatment failure was 3.0% in the urgent endoscopy group and 2.9% in the early group ( p = 0.90). The in-hospital mortality was 1.9% in the urgent endoscopy group and 1.2% in the early endoscopy group ( p = 0.26). The incidence of need for intensive care unit was 18.2% in the urgent endoscopy group and 21.4% in the early endoscopy group ( p = 0.11). The mean length of hospital stay was 17.9 days in the urgent endoscopy group and 12.9 days in the early endoscopy group ( p < 0.05). The incidence of 5-day treatment failure in the <12-hour group was 2.3% and 2.2% in the 12-24 hours group ( p = 0.85). The in-hospital mortality was 2.2% in the <12-hour group and 0.5% in the 12-24 hours group ( p < 0.05). CONCLUSIONS: The data suggest that performance of endoscopy within 6-12 or within 24 hours of presentation among patients with cirrhosis with AVB led to similar treatment failure outcomes.
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Varizes Esofágicas e Gástricas , Hemorragia Gastrointestinal , Humanos , Estudos de Coortes , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/complicações , Estudos Retrospectivos , Cirrose Hepática/complicações , Endoscopia GastrointestinalRESUMO
BACKGROUND: Estrogen receptor ß (ERß) is the major ER subtype in hepatic stellate cells (HSCs). Previously we reported phytoestrogen calycosin suppressed liver fibrosis progression and inhibited HSC-T6 cell functions, suggesting the effects may be related to ERß. Here, we explore the effect of overexpressed ERß on human HSCs and the role of ERß in pharmacological action of calycosin. METHODS: LX-2 cells were transfected with lentivirus to overexpress ERß. In the presence or absence of overexpressed ERß, the effects of ERß and calycosin on proliferation, migration, activation, collagen production and degradation of TGF-ß1-induced LX-2 cells and the role of ERß in the inhibition effect of calycosin were investigated. LX-2 cells overexpressed with ERß or treated with ER non-selective antagonist ICI182,780 were used to investigate the regulation of ERß on JAK2/STAT3 signaling pathway. CCK-8 method was used to screen effective doses of calycosin and investigate cell proliferation. The cell migration was detected by transwell chamber assay. The expression of α-SMA was detected by immunofluorescence and western blot. The protein expressions of Col-I, MMP1, TIMP1, JAK2, p-JAK2, STAT3 and p-STAT3 were detected by western blot. RESULTS: ERß overexpressed lentivirus was successfully transfected into LX-2 cells with high efficiency. Overexpressed ERß or calycosin alone inhibited the TGF-ß1-induced LX-2 cell proliferation and migration, downregulated the protein expressions of α-SMA, Col-I, TIMP-1, p-STAT3 and upregulated MMP-1. Both overexpressed ERß and calycosin had no significant effect on JAK2, p-JAK2 and STAT3 expressions. ERß overexpression further enhanced the above effects of calycosin. However, after the cells were treated with ICI182,780, downregulation of STAT3 phosphorylation induced by calycosin was reversed. CONCLUSIONS: ERß mediated the inhibition of major functions of LX-2 cell possibly by inhibiting the phosphorylation of STAT3, and was an important pathway through which calycosin exerted anti-liver fibrosis effect.
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Receptor beta de Estrogênio , Células Estreladas do Fígado , Proliferação de Células , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Receptor beta de Estrogênio/uso terapêutico , Fibrose , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Isoflavonas , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 1 da Matriz/farmacologia , Metaloproteinase 1 da Matriz/uso terapêutico , Fosforilação , Fitoestrógenos/farmacologia , Fator de Transcrição STAT3 , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-1/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/uso terapêuticoRESUMO
Background and Aims: Emergency endoscopy is recommended for patients with acute esophageal variceal bleeding (EVB) and their prognosis has improved markedly over past decades due to the increased specialization of endoscopic practice. The study aimed to compare outcomes following emergency endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) in cirrhotic patients with acute EVB. Methods: Cirrhotic patients with acute EVB who underwent emergency endoscopy were retrospectively enrolled from 2013 to 2020 across 34 university hospitals from 30 cities. The primary outcome was the incidence of 5-day rebleeding after emergency endoscopy. Subgroup analysis was stratified by Child-Pugh class and bleeding history. A 1:1 propensity score matching (PSM) analysis was performed. Results: A total of 1,017 and 382 patients were included in EIS group and EVL group, respectively. The 5-day rebleeding incidence was similar between EIS group and EVL group (4% vs. 5%, P = 0.45). The result remained the same after PSM (P = 1.00). Among Child-Pugh class A, B and C patients, there were no differences in the 5-day rebleeding incidence between the two groups after PSM (P = 0.25, 0.82, and 0.21, respectively). As for the patients with or without bleeding history, the differences between EIS group and EVL group were not significant after PSM (P = 1.00 and 0.26, respectively). Conclusion: The nationwide cohort study indicates that EIS and EVL are both efficient emergency endoscopic treatment strategies for acute EVB. EIS should not be dismissed as an economical and effective emergency endoscopic treatment strategy of acute EVB. ClincialTrials.gov number NCT04307264.
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OBJECTIVE: To explore diagnosis and surgical treatment of symptomatic lumbar spinal epidural lipoplasia. METHODS: A retrospective analysis of 19 patients with symptomatic lumbar spinal epidural hyperplasia treated with hemilaminectomy and interbody fusion and internal fixation from February 2012 to November 2018 were performed, including 7 males and 12 females, aged from 48 to 72 years old with an average of (57.6±1.2) years old;the course of disease ranged from 6 to 60 months with an average of (18.6±5.1) months;plane requiring decompression:L2, 3-L5S1 on 4 cases, L2, 3-L4, 5 on 5 cases, L3, 4-L4, 5 on 2 cases, L3, 4-L5S1 on 6 cases, L4, 5-L5S1 on 2 cases. Visual analogue scale (VAS) before operation and 6 months after opertaionwere used to evaluate relief of leg pain and back pain, Oswestry Disability Index (ODI) was used to evaluate recovery of functiona, and Fischgrund was used to assess overall efficacy. RESULTS: All patients were followed up from 12 to 37 months with an average of (16.3±3.8) months. Ninteen patients were successfully completed operation, and all adipose tissues in the compressed segment of the spinal canal were removed. Operation time was from 125 to 260 min with an average of (186± 15) min, and blood bleeding was from 150 to 500 ml with an average of (280±46) ml. Two patients occurred partial incision fat liquefaction and exudate did not heal, the incision was opened to remove effusion, the dressing was changed and anti-inflammatory treatments were performed. No complications such as cauda equina injury, cerebrospinal fluid leakage, and broken nails occurred. Preopertaive VAS of back pain and leg pain were 5.3±0.7 and 6.8±0.8, respectively, while 2.1±0.4 and 2.3±0.5 respectively at 6 months after opertaion, there were statisticalsignificant difference between 6 months after operation and before operation (P<0.05). Postoperative ODI score at 6 months was 12.1±2.3, and significantly improved than that of before operation 45.5±2.8 (P<0.05). According to Fischgrund criteria, 13 patients got excellent result, 4 good, and 2 fair. CONCLUSION: Patients with symptomatic lumbar spinal epidural lipoplasia undergo hemilaminectomy and internal fixation of compression segment could relieve compression of dura mater and cauda equina, and achieve good clinical results.
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Fusão Vertebral , Dor nas Costas , Pré-Escolar , Feminino , Humanos , Lactente , Vértebras Lombares/cirurgia , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the diagnosis, treatment, cause and prevention of nerve compression by bone fragment after lumbar spine surgery. METHODS: The clinical data of 23 patients with nerve compression by bone fragment after lumbar spine surgery from February 2012 to March 2019 were collected retrospectively, including 9 males and 14 females, aged 42 to 81 years with an average of (62.60±5.70) years. The surgical methods included lumbar interbody fusion in 20 cases and spinal endoscopy in 3 cases. All 23 patients experienced radiating pain on the decompression side or the contralateral limb after operation. The time of occurrence was from immediately after operation to 2 weeks after operation, with an average of (3.2±1.7) days. All patients underwent postoperative examination of lumbar spine CT or MRI to confirm residual ectopic bone fragments, and at the same time, bilateral lower extremity color Doppler ultrasound excluded thrombosis. Sources of ectopic bone fragments:14 cases of residual bone fragments caused by intervertebral fusion bone graft loss or fenestration fusion, 6 cases of fractured upper articular process head, and 3 cases of upper articular process bone remaining during spinal endoscopic surgery. RESULTS: The patient's hospital stay was 10 to 37 (23.4±6.2) days. All patients were followed up for 6 to 25 (13.6±3.4) months. Three patients underwent posterior open nerve root exploration for removing bone fragments on the same day or the second day after surgery, and the symptoms were relieved. Twenty patients underwent conservative treatment firstly, and 13 patients were discharged after pain relieved by conservative treatment, 7 patients failed conservative treatment, the 2 cases of failed 7 cases had undergone nerve root block surgery during conservative treatment. Two patients underwent spinal endoscopy nerve root exploration and bone mass removal, and five patients underwent posterior open nerve root exploration and bone fragmentation removal. All postoperative pain symptoms were relieved. Preoperative CT, MRI and intraoperative bone fragment removal confirmed the shape and location of the bone fragments. The most likely source of bone fragments was the loss of intervertebral fusion bone grafts or residual bone fragments resulting from fenestration fusion (14 cases), fractured upper articular process head (6 cases), and upper articular process bones remaining in endoscopic surgery (3 cases). According to the Macnab criteria in evaluating clinical outcome, 20 cases got excellent results and 3 good. CONCLUSION: After the lumbar spine surgery, the nerve compression by bone fragments is treated with appropriate treatments, and good clinical results can be obtained. Timely removal of residual bone fragments during operation and careful exploration of nerve roots before closing incision can avoid such complications.
Assuntos
Vértebras Lombares , Fusão Vertebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Descompressão Cirúrgica , Endoscopia , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the feasibility and clinical effect of hemi-resection of posterior arch of atlas in the upper cervical spinal dumbbell-shaped schwannomas. METHODS: A retrospective analysis was performed on 13 patients with high level cervical dumbbell schwannomas from January 2005 to December 2018, including 10 males and 3 females, aged 19 to 67 years old. The occipital foramen to the C1 were 4 cases and 9 cases of C1,2. Tumors were removed by posterior arch of the atlas resection without internal fixation. The clinical efficacy was evaluated by visual analogue pain scale (VAS), Japanese Orthopaedic Association (JOA) scores, and American Spinal Injury Association(ASIA) ratings. RESULTS: The operation was successfully completed in 13 cases of this group. No vertebral artery injury or spinal cord injury occurred during the operation. All 13 patients were followed up for more than 12 months. No local recurrence was found. Both the VAS and the JOA score were significantly improved compared with those before surgery. The ASIA classification before operation was:1 case of grade C, 6 cases of grade D, 6 cases of grade E;the latest follow up was 3 cases of ASIA grade D and 10 cases of E. CONCLUSION: The posterior arch of the atlas hemisection can remove the upper cervical dumbbell schwannoma in one stage. The short-term clinical effect is good, and there are no complications such as cervical instability.
Assuntos
Vértebras Cervicais , Neurilemoma , Adulto , Idoso , Feminino , Fixação Interna de Fraturas , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To study the changes of anterior soft tissue swelling after anterior cervical subtotal corpectomy, titanium mesh fusion and internal fixation. METHODS: From November 2015 to July 2018, 151 patients with cervical spondylotic myelopathy were treated with anterior single corpectomy, titanium mesh fusion and internal fixation, including 109 males and 42 females, aged 44 to 81 (59.77±8.34) years. Through postoperative follow up observation, the C2-C7 level of anterior intervertebral space distance was measured to evaluate the changes of anterior soft tissue swelling. RESULTS: All patients were followed up for 15 to 40(28.00±3.52) months. One week after the operation, the swelling of anterior soft tissue reached the peak, and then decreased. At 8 months after the operation, the swelling of anterior soft tissue on C5, C6 and C7 plane returned to normal. At 12 months after the operation, the swelling of anterior soft tissue on C2, C3 and C4 plane returned to normal. CONCLUSION: Anterior subtotal cervical corpectomy, titanium mesh bone graft fusion and internal fixation can cause swelling of the anterior soft tissue. One week after operation, we should pay more attention to the aggravation of the swelling of the anterior soft tissue to avoid the occurrence of dysphagia, respiratory obstruction, asphyxia and other complications.
Assuntos
Doenças da Medula Espinal , Fusão Vertebral , Espondilose , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Gastric carcinoma (GC) remains one of the most common and deadly cancers worldwide. In China, the incidence and mortality rates related to GC were quite high. Annexin A8 (ANXA8) is a member of the annexins family of calcium-dependent membrane phospholipid binding proteins. According to recent research, the up-regulation of ANXA8 is closely associated with various types of tumors. However, the specific role of ANXA8 in GC remains unclear. In our study, we explored the prognostic value of ANXA8 in GC. Here, with the data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE19826 and GSE13861) analyzed, we further performed quantitative real-time polymerase chain reaction (qRT-PCR) using 58 pairs of fresh-frozen tissues. We also subjected 152 pairs of formalin-fixed, paraffin-embedded GC tumor tissues from patients, and the adjacent normal gastric tissues (ANGTs) to immunohistochemical (IHC) analysis. Hence, we found an elevated expression of ANXA8 in tumor tissues with bioinformatics analyses, qRT-PCR, western blot and IHC. Over-expression of ANXA8 was strongly correlated with TNM stages and differentiation grades. Kaplan-Meier and cox proportional-hazard analyses showed that the increased expression of ANXA8 was strongly associated with overall survival (OS) and disease-free survival (DFS) in GC patients. Moreover, we found that ANXA8 is an independent prognostic factor of GC patients' OS and DFS. In brief, those results suggest that ANXA8 can act as an oncogene of GC development and can serve as a potential prognostic biomarker for GC treatment.