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1.
Nature ; 607(7918): 276-280, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35831597

RESUMO

One of the main developments in unconventional superconductivity in the past two decades has been the discovery that most unconventional superconductors form phase diagrams that also contain other strongly correlated states. Many systems of interest are therefore close to more than one instability, and tuning between the resultant ordered phases is the subject of intense research1. In recent years, uniaxial pressure applied using piezoelectric-based devices has been shown to be a particularly versatile new method of tuning2,3, leading to experiments that have advanced our understanding of the fascinating unconventional superconductor Sr2RuO4 (refs. 4-9). Here we map out its phase diagram using high-precision measurements of the elastocaloric effect in what we believe to be the first such study including both the normal and the superconducting states. We observe a strong entropy quench on entering the superconducting state, in excellent agreement with a model calculation for pairing at the Van Hove point, and obtain a quantitative estimate of the entropy change associated with entry to a magnetic state that is observed in proximity to the superconductivity. The phase diagram is intriguing both for its similarity to those seen in other families of unconventional superconductors and for extra features unique, so far, to Sr2RuO4.

2.
Proc Natl Acad Sci U S A ; 118(10)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33653958

RESUMO

A key question regarding the unconventional superconductivity of [Formula: see text] remains whether the order parameter is single- or two-component. Under a hypothesis of two-component superconductivity, uniaxial pressure is expected to lift their degeneracy, resulting in a split transition. The most direct and fundamental probe of a split transition is heat capacity. Here, we report measurement of heat capacity of samples subject to large and highly homogeneous uniaxial pressure. We place an upper limit on the heat-capacity signature of any second transition of a few percent of that of the primary superconducting transition. The normalized jump in heat capacity, [Formula: see text], grows smoothly as a function of uniaxial pressure, favoring order parameters which are allowed to maximize in the same part of the Brillouin zone as the well-studied van Hove singularity. Thanks to the high precision of our measurements, these findings place stringent constraints on theories of the superconductivity of [Formula: see text].

3.
Cardiovasc Diabetol ; 22(1): 157, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37386500

RESUMO

BACKGROUND: Although there is numerous evidence on the epidemiological risk factors for insulin resistance (IR)-related metabolic diseases, there is still insufficient evidence to explore the non-linear association of Atherogenic Index of Plasma (AIP) with IR. Therefore, we aimed to elucidate the non-linear relationship between AIP and IR and type 2 diabetes (T2D). METHODS: This cross-sectional study was conducted in the National Health and Nutrition Survey (NHANES) from 2009 to 2018. A total of 9,245 participants were included in the study. The AIP was calculated as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included IR and T2D defined by the 2013 American Diabetes Association guidelines. The weighted multivariate linear regression, weighted multivariate logistic regression, subgroup analysis, generalized additive model, smooth fitting curve and two-part logistic regression were adopted to reveal the relationship of AIP with IR and T2D. RESULTS: After adjustment for age, gender, race, education level, smoking status, alcohol consumption, vigorous/moderate physical activity, body mass index, waist circumference and hypertension, we found that AIP was positively associated with fasting blood glucose (ß = 0.08, 95% CI: 0.06, 0.10), glycosylated hemoglobin (ß = 0.04, 95% CI: 0.39, 0.58), fasting serum insulin (ß = 4.26, 95% CI: 3.73, 4.79), and homeostasis model assessment of insulin resistance (ß = 0.22, 95% CI: 0.18, 0.25). Further studies found that AIP was associated with increased risk of IR (OR = 1.29, 95% CI: 1.26-1.32) and T2D (OR = 1.18, 95% CI: 1.15-1.22). However, the positive association between AIP and IR or T2D was more significant in female than in male (IR: P for interaction = 0.0135; T2D: P for interaction = 0.0024). A non-linear and inverse L-shaped association was found between AIP and IR, while a J-shaped association was found between AIP and T2D. In patients with - 0.47 < AIP < 0.45, increased AIP was significantly associated with increased risk of IR and T2D. CONCLUSIONS: AIP showed an inverse L-shaped association with IR and a J-shaped association with T2D, indicating that AIP should be reduced to a certain level to prevent IR and T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Feminino , Masculino , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Transversais , Inquéritos Nutricionais , Fatores de Risco
4.
Molecules ; 28(9)2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-37175058

RESUMO

Cutting fluids are the most effective method to lower the cutting temperature and decrease the cutting tool wear. At the same time, the cutting fluids influence the corrosion resistance property of the machined surface. In this study, chlorinated paraffin (CP), which is a common additive in the cutting fluid, was selected as the research objective to study its corrosion resistance property. The passivation effect of CP with different concentrations on the machined surface of stainless steel was studied. Electrochemical measurements and surface morphology investigation were used to characterize the passivation effect of CP with different concentrations. The test results showed that the corrosion resistance of stainless steel in the cutting fluid was enhanced with the increase in CP additive. This reason is that the charge transfer resistance increases and the corrosion current density decreases with the increase in CP additive. The X-ray photoelectron spectroscopy (XPS) results show that the proportion of metal oxides on the processed surface of the stainless steel sample was increased from 20.4% to 22.0%, 32.9%, 26.6%, and 31.1% after adding 1 mL, 2 mL, 4 mL and 6 mL CP in the cutting fluid with a total volume of 500 mL, respectively. The oxidation reaction between CP and the stainless steel sample resulted in an increase in metal oxides proportion, which prevented the stainless steel sample from corrosion in cutting fluid.

5.
J Surg Res ; 271: 24-31, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34814049

RESUMO

BACKGROUND: To delineate the clinical characteristics of intestinal fistula patients with Bloodstream infection (BSI). METHODS: Retrospective case series in Surgical Intensive Care Unit (SICU), Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Among a cohort of 204 patients with a diagnosis of intestinal fistula, 46 who were complicated with BSI were analysed retrospectively. Data was collected from January 1, 2018 to February 1, 2020. RESULTS: Among the 204 patients with intestinal fistula, 46 patients showed positive blood cultures, which clearly had BSIs. Parenteral nutrition (PN) time (OR 1.08, 95% CI 1.04∼1.12, P < 0.01), transferred from external ICU (OR 3.68, 95% CI 1.48∼9.17, P = 0.01), septic shock (OR 4.61, 95% CI 1.77∼11.97, P < 0.01), APACHE II (OR 1.11, 95% CI 1.01∼1.22, P = 0.04) were significantly associated with BSI in patients with intestinal fistula. When APACHE II score exceeds 12.0 points or PN time exceeds 18.0 D, the chance of BSI in patients with intestinal fistula increases significantly. In addition, compared with the non-BSI group, BSI group had a higher mortality and expenses in ICU, longer stay in ICU and total hospital stay, and worse quality of life (all P < 0.05). A total of 105 isolates from samples (including sputum, pus and blood) of 46 patients in the BSI group, among which were mainly gram negative rods and fungi, as well as blood isolates. Importantly, in patients with intestinal fistula, BSIs caused by fungi accounted for 23.4%. CONCLUSION: Long-term PN, transfer from external ICU, septic shock, and higher APACHE II scores are often associated with an increased probability of BSIs in patients with intestinal fistula and a higher mortality. Gram-negative bacteria are the main pathogenic bacteria in intestinal fistula patients with BSI, and patients with intestinal fistula are more likely to develop fungal BSIs.


Assuntos
Bacteriemia , Infecção Hospitalar , Fístula Intestinal , Sepse , Bacteriemia/complicações , China/epidemiologia , Infecção Hospitalar/microbiologia , Humanos , Fístula Intestinal/complicações , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Sepse/complicações
6.
Int J Cancer ; 147(9): 2634-2644, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32441314

RESUMO

Intravasation, vascular dissemination and metastasis of malignant tumor cells require their passage through the vascular wall which is commonly composed of pericytes and endothelial cells. We currently decided to investigate the relative contribution of these cell types to B16F10 melanoma metastasis in mice using an experimental model of host Shb gene (Src homology 2 domain-containing protein B) inactivation. Conditional inactivation of Shb in endothelial cells using Cdh5-CreERt2 resulted in decreased tumor growth, reduced vascular leakage, increased hypoxia and no effect on pericyte coverage and lung metastasis. RNAseq of tumor endothelial cells from these mice revealed changes in cellular components such as adherens junctions and focal adhesions by gene ontology analysis that were in line with the observed effects on leakage and junction morphology. Conditional inactivation of Shb in pericytes using Pdgfrb-CreERt2 resulted in decreased pericyte coverage of small tumor vessels with lumen, increased leakage, aberrant platelet-derived growth factor receptor B (PDGFRB) signaling and a higher frequency of lung metastasis without concomitant effects on tumor growth or oxygenation. Flow cytometry failed to reveal immune cell alterations that could explain the metastatic phenotype in this genetic model of Shb deficiency. It is concluded that proper pericyte function plays a significant role in suppressing B16F10 lung metastasis.


Assuntos
Neoplasias Pulmonares/genética , Melanoma Experimental/genética , Pericitos/patologia , Proteínas Proto-Oncogênicas/deficiência , Neoplasias Cutâneas/patologia , Junções Aderentes/patologia , Animais , Células Endoteliais/metabolismo , Adesões Focais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Pulmão/citologia , Pulmão/patologia , Neoplasias Pulmonares/secundário , Melanoma Experimental/secundário , Camundongos , Pericitos/citologia , Proteínas Proto-Oncogênicas/genética , RNA-Seq , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais/genética , Neoplasias Cutâneas/genética
7.
Biochem Biophys Res Commun ; 523(3): 645-650, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-31941599

RESUMO

Vitamin D deficiency and refractory osteoporosis are common complications in patients with short bowel syndrome (SBS). The symptom of bone loss is not effectively alleviated, even after the oral administration of vitamin D in SBS patients who had been weaned off parenteral nutrition. In this study, we aimed to investigate the effect of propionate on the expression of the vitamin D receptor (VDR) in the small intestine of rats with SBS. Firstly, IEC-6 (intestinal epithelioid cell line No. 6) cells were incubated in vitro with 1 mM sodium propionate for 24 h. This resulted in a significant increase in the expression of VDR and yes-associated protein (YAP) compared with that in the control group. Transfection of IEC-6 cells with YAP siRNA significantly down-regulated the expression of VDR. By contrast, after incubating IEC-6 cells with lysophosphatidic acid, an agonist of YAP, upregulation of VDR and YAP was observed. Next, we investigated whether this effect occurs in vivo. Five-week-old male Sprague-Dawley rats underwent 80% small bowel resection to establish an SBS model. Rats treated with 1% w/v sodium propionate had high levels of VDR and YAP expression in the intestine and intestinal adaptation was clearly observed compared to the control group. However, these effects were blocked by intraperitoneal injection of verteporfin. Thus, this study showed that propionate promoted VDR expression in the intestine via the activity of YAP, both in vitro and in vivo. Moreover, propionate was shown to play an active role in postoperative intestinal adaptation in SBS rats.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Propionatos/farmacologia , Receptores de Calcitriol/genética , Síndrome do Intestino Curto/tratamento farmacológico , Regulação para Cima/efeitos dos fármacos , Animais , Proteínas Reguladoras de Apoptose/análise , Linhagem Celular , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Propionatos/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptores de Calcitriol/análise , Síndrome do Intestino Curto/genética , Síndrome do Intestino Curto/patologia , Proteínas de Sinalização YAP
8.
Dig Dis Sci ; 65(2): 431-441, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31441001

RESUMO

BACKGROUND: Short bowel syndrome (SBS) resulting from extensive intestinal resection is thought to significantly affect gut microbiota. Data are limited on the signatures of the intestinal microbiome in SBS with different anatomical types. AIMS: The aim of our investigation was to characterize the composition and function of gut microbiota in SBS with or without ileocecal resection (ICR). METHODS: Six-week-old male Sprague-Dawley rats underwent 75% small bowel resection (SBR) with the ileocecal junction intact (SBR group, jejunoileal anastomosis, n = 10) or removed (ICR group, jejunocolic anastomosis, n = 10), or sham surgery (sham group, n = 10). Colonic contents of the rats were collected 28 days after operation, and 16S rRNA gene sequencing was performed on the MiSeq Illumina platform to analyze bacterial composition. RESULTS: Overall structures of the gut microbiome differed significantly among the three groups. The bacterial α-diversity of the ICR group was remarkably lower than that of the sham group. ICR rats were enriched with Lactobacillus and opportunistic pathogens from Proteobacteria but depleted of commensal genera belonging to the Lachnospiraceae, Ruminococcaceae and Erysipelotrichaceae families. Genera from the Bacteroidales S24-7 group, Porphyromonadaceae, Prevotellaceae, Rikenellaceae and Christensenellaceae were prevalent in SBR rats. Functional pathways of branched-chain and aromatic amino acid biosynthesis, lipopolysaccharide biosynthesis and infectious diseases were abundant in the ICR group, while SBR rats featured pathways of C5 branched dibasic acid metabolism, biotin metabolism and one carbon pool folate. CONCLUSIONS: ICR causes dramatically more severe intestinal dysbiosis than SBR only in SBS rat models, resulting in altered functional profiles of the gut microbiome.


Assuntos
Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Síndrome do Intestino Curto/microbiologia , Anastomose Cirúrgica , Animais , Ceco/cirurgia , Clostridiales , Colo/microbiologia , Colo/cirurgia , Disbiose/etiologia , Disbiose/metabolismo , Microbioma Gastrointestinal/fisiologia , Íleo/cirurgia , Jejuno/cirurgia , Lactobacillus , Masculino , Proteobactérias , RNA Ribossômico 16S , Ratos , Índice de Gravidade de Doença , Síndrome do Intestino Curto/complicações , Síndrome do Intestino Curto/metabolismo
9.
Artif Organs ; 44(10): 1098-1106, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32279328

RESUMO

Extracorporeal membrane oxygenation (ECMO) could ameliorate the energy status and viability of bowel grafts from cardiac death donors. However, the function of these grafts after transplantation is not clear. The purpose of the study was to evaluate the early function of intestinal grafts after transplantation from expected cardiac death donors supported with normothermic extracorporeal support using a porcine allogeneic orthotopic segmental small bowel transplantation model. Eighteen domestic crossbred donor pigs were assigned to living donation (LD), donation after cardiac death (DCD), and ECMO groups. In the LD group, small bowels were harvested and preserved immediately in cold storage. In the other two groups, the donor pigs received conventional rapid recovery treatment or 1-hour normothermic extracorporeal support after 10-minutes expected cardiac arrest. Subsequently, the small bowels were removed and preserved in cold storage. After 5-6 hours of preservation, small bowel grafts were transplanted into the recipient pigs that underwent enterectomy. The pathology and electron microscopy results, cell apoptosis rate, tight junction protein expression level in the intestinal mucosa, and plasma endotoxin level were evaluated after transplantation. All grafts functioned on the basis of the maltose absorption test results at day 7 after transplantation. There were no significant differences in the morphological changes in the intestinal mucosa among the three groups at day 7 after transplantation. The cell apoptosis rate and plasma endotoxin level in the ECMO group did not differ significantly than those in the LD group, but were evidently lower than those in the DCD group (P < .001). The intestinal absorptive function improved significantly in the ECMO group in contrast with that in the DCD group (P < .001). Short-term ECMO intervention can alleviate ischemia-reperfusion injuries in intestinal grafts and improve intestinal absorptive function in the early stage after transplantation. Reducing caspase-3 protein expression and cell apoptosis in the intestinal mucosa may be one of the protective mechanisms of ECMO intervention.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Intestinos/transplante , Preservação de Órgãos/métodos , Traumatismo por Reperfusão/prevenção & controle , Coleta de Tecidos e Órgãos/métodos , Aloenxertos/irrigação sanguínea , Aloenxertos/patologia , Aloenxertos/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , Sobrevivência de Enxerto/fisiologia , Parada Cardíaca/fisiopatologia , Humanos , Intestinos/irrigação sanguínea , Intestinos/patologia , Intestinos/fisiopatologia , Doadores Vivos , Masculino , Modelos Animais , Perfusão/métodos , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Sus scrofa , Transplante Homólogo/métodos
10.
Trop Med Int Health ; 24(1): 81-90, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30338607

RESUMO

OBJECTIVES: Intestinal tuberculosis (ITB) remains prevalent and a big health hazard in China. The aim of this study was to retrospectively analyse its clinico-pathological features. METHODS: Retrospective study of 85 consecutive ITB patients in two tertiary hospitals in East China. Relevant clinical, laboratory examination, radiological, endoscopic and histopathological features of ITB were recorded. RESULTS: The mean age was 37.3 ± 16.0 years; 56 patients (65.9%) were male. 67.1% had ITB secondary to pulmonary tuberculosis. The overall median length of hospital stay was 28 days and was significantly longer in patients with intestinal complications (P = 0.003) and malnutrition (P = 0.042). Abdominal pain (88.2%) and weight loss (75.3%) were the commonest symptoms. The positive rate of the purified protein derivative (PPD) test was 88.2%; of the T-spot, 85.7%. Histopathology revealed caseating granuloma in 70.6% and caseating necrosis in 24.7% of patients. The most commonly affected sites were the ileocecal valve (56, 65.9%), terminal ileum (40, 47.1%) and caecum (33, 38.8%). Only 17 (20%) patients were initially diagnosed as ITB, the other 68 patients were misdiagnosed. Six patients with caecum tuberculosis were misdiagnosed as appendicitis, four of whom had improper surgical procedures followed by post-operative intestinal fistulas; two died due to MODS. CONCLUSIONS: Diagnosis of ITB is often misdirected and delayed, which may lead to inappropriate treatment and high mortality. High diagnostic suspicion is necessary for patients with unexplained abdominal complaints. Diagnosis is not easy but could benefit coexisting pulmonary tuberculosis, T-spot, CT imaging, colonoscopy, pathological features, acid-fast bacilli and response to anti-tuberculosis therapy (ATT).


Assuntos
Dor Abdominal/etiologia , Teste Tuberculínico/métodos , Tuberculose Gastrointestinal/diagnóstico , Adulto , Anemia/etiologia , China , Diarreia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculose Gastrointestinal/patologia , Redução de Peso
11.
Ann Nutr Metab ; 75(1): 47-54, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31434099

RESUMO

INTRODUCTION: Patients with short bowel syndrome (SBS) commonly develop nephrolithiasis. However, the risk factors for nephrolithiasis in patients with SBS remain unclarified. The present study aimed to identify the risk factors for nephrolithiasis in adults with SBS. METHODS: All eligible adults diagnosed with SBS and admitted to a tertiary referral center from December 2008 to 2018 were retrospectively identified from a prospectively maintained database. Patients' demographic and clinical characteristics were analyzed using univariate and multivariate analyses to identify the risk factors for nephrolithiasis. RESULTS: Of 231 adults with SBS, 42 (18.2%) developed nephrolithiasis. The mean age was 46.4 ± 17.8 years, the mean body mass index was 18.2 ± 3.8 kg/m2, and median duration of SBS was 11 months (range 2-324 months). Multivariate binary logistic regression analysis revealed that the independent risk factors for nephrolithiasis in adults with SBS were jejuno-ileal anastomosis and colon-in-continuity (OR 4.335; 95% CI 1.175-16.002; p = 0.028), prolonged duration of SBS (OR 1.008; 95% CI 1.002-1.014; p = 0.010), and increased serum creatinine concentration (OR 1.005; 95% CI 1.001-1.009; p = 0.012). CONCLUSIONS: Nephrolithiasis is common in adults with SBS. As nephrolithiasis can have adverse clinical consequences, patients with SBS should be closely monitored, and prophylactic interventions should be considered.


Assuntos
Nefrolitíase/etiologia , Síndrome do Intestino Curto/complicações , Adulto , Anastomose Cirúrgica/efeitos adversos , Creatinina/sangue , Feminino , Humanos , Intestinos/patologia , Intestinos/cirurgia , Jejunostomia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nefrolitíase/diagnóstico , Nefrolitíase/prevenção & controle , Fatores de Risco , Síndrome do Intestino Curto/patologia , Fatores de Tempo
12.
Cell Physiol Biochem ; 49(6): 2163-2173, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30286467

RESUMO

BACKGROUND/AIMS: the pathogenesis of sepsis-associated encephalopathy (SAE) is multifactorial, involving neurotransmitter alterations, inflammatory cytokines, oxidative damage, mitochondrial dysfunction, apoptosis, and other factors. Mitochondria are major producers of reactive oxygen species, resulting in cellular injury. Omi/HtrA2 is a proapoptotic mitochondrial serine protease involved in caspase-dependent cell death; it is translocated from mitochondria to the cytosol after an apoptotic insult. We previously found that UCF-101, a specific inhibitor of Omi/HtrA2, has neuroprotective effects on cerebral oxidative injury and cognitive impairment in septic rats. In this study, the mechanisms and molecular pathways underlying these effects were investigated. METHODS: Male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP) or sham-operated laparotomy and were administered vehicle or UCF-101 (10 µmol/kg). The hippocampus was isolated for subsequent analysis. Omi/HtrA2 expression in the mitochondria or cytosol was evaluated by immunofluorescence or western blotting. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining was utilized to evaluate levels of apoptosis, and western blotting was used to evaluate apoptosis-related proteins, such as cleaved caspase-3, caspase-9, and poly (ADP-ribose) polymerase (PARP). Tight junction expression was assessed by immunofluorescence and western blotting. Mitochondrial function, inflammatory cytokines, and oxidative stress were also assayed. In addition, a wet/dry method was used to evaluate brain edema and Evans blue extravasation was used to evaluate blood-brain barrier (BBB) integrity. RESULTS: After CLP treatment, the hippocampus exhibited a mild increase in Omi/HtrA2 expression; cytosolic Omi/HtrA2 expression increased significantly, whereas mitochondrial Omi/HtrA2 expression was reduced, indicating that CLP-induced oxidative stress resulted in the translocation of Omi/HtrA2 from mitochondria to the cytosol. Hippocampal cleaved caspase-3, caspase-9, and PARP levels were significantly higher in animals treated with CLP than in sham-operated animals, while XIAP expression was lower. Treatment with UCF-101 prevented the mobilization of Omi/HtrA2 from mitochondria to the cytosol, attenuated XIAP degradation, and decreased cleaved caspase-3, caspase-9, and PARP expression as well as apoptosis. UCF-101 also reversed the decreased mitochondrial complex I, II, and III respiration and the reduced ATP caused by CLP. In addition, UCF-101 treatment resulted in a significant improvement in BBB integrity, as demonstrated by increased occludin, claudin-5, and zonula occludens 1 levels and reduced Evans blue extravasation. No significant effects of UCF-101 on brain edema were found. Inflammatory cytokines and oxidative stress were significantly higher in the CLP-treated group than in the sham-operated group. However, the inhibition of Omi/HtrA2 by UCF-101 significantly alleviated these responses. CONCLUSION: Our data indicated that Omi/ HtrA2 regulates a mitochondria-dependent apoptotic pathway in a murine model of septic encephalopathy. Inhibition of Omi/HtrA2 by UCF-101 leads to neuroprotection by inhibiting the cytosolic translocation of Omi/HtrA2 and antagonizing the caspase-dependent apoptosis pathway. Therapeutic interventions that inhibit Omi/HtrA2 translocation or protease activity may provide a novel method to treat SAE.


Assuntos
Apoptose , Serina Peptidase 2 de Requerimento de Alta Temperatura A/metabolismo , Mitocôndrias/metabolismo , Sepse/patologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Citosol/metabolismo , Modelos Animais de Doenças , Dinaminas/genética , Dinaminas/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , GTP Fosfo-Hidrolases , Serina Peptidase 2 de Requerimento de Alta Temperatura A/antagonistas & inibidores , Serina Peptidase 2 de Requerimento de Alta Temperatura A/genética , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Malondialdeído/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Ocludina/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Pirimidinonas/farmacologia , Ratos , Ratos Sprague-Dawley , Tionas/farmacologia , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
13.
J Gastroenterol Hepatol ; 32(12): 1949-1957, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28425133

RESUMO

BACKGROUND AND AIM: Short bowel syndrome (SBS) is a common cause of intestinal failure and can be divided into three types depending on intestinal anatomy. Gut dysbiosis has been observed in pediatric SBS patients and is associated with impaired outcome. Little is known about the changes in gut microbiota of adult SBS patients. Therefore, we aim to characterize the fecal microbiota of adult patients with different types of SBS. METHODS: Fifteen fecal samples from healthy controls and adult patients with type II or type III SBS were collected (five in each group). Fecal microbial compositions were determined by high-throughput sequencing, and functional potential was predicted by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. RESULTS: Bacterial α-diversity significantly decreased in SBS patients and positively correlated to the remaining small bowel length. SBS II patients were enriched with Proteobacteria but deficient in Firmicutes and Bacteroidetes. Whereas Lactobacillus and Prevotella dominated the microbiomes of SBS III patients, commensal bacteria from Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae declined in SBS patients. The parenteral nutrition duration of SBS patients was positively related to the proportion of Enterobacteriaceae but negatively related to Lactobacillus. Functional pathways of citrate cycle and branched-chain and aromatic amino acid biosynthesis were abundant in SBS II patients, while functional profiles of pyrimidine and purine metabolism were dominant in SBS III patients. CONCLUSIONS: Short bowel syndrome patients have a marked intestinal dysbiosis with type II SBS characterized by Proteobacteria and type III SBS featured by Lactobacillus, resulting in altered functional profiles of fecal microbiomes.


Assuntos
Fezes/microbiologia , Microbioma Gastrointestinal , Síndrome do Intestino Curto/microbiologia , Adulto , Aminoácidos Aromáticos/biossíntese , Aminoácidos de Cadeia Ramificada/biossíntese , Estudos de Casos e Controles , Ciclo do Ácido Cítrico , Disbiose , Feminino , Humanos , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Lactobacillus , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Purinas/metabolismo , Pirimidinas/metabolismo , Síndrome do Intestino Curto/classificação , Síndrome do Intestino Curto/metabolismo
14.
J Surg Res ; 204(2): 335-343, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27565069

RESUMO

BACKGROUND: Surgery is required in approximately one-third of patients with chronic radiation enteritis (CRE). The aim of this study was to explore the short- and long-term outcomes after surgery for CRE and risk factors of postoperative morbidity. METHODS: Clinical features and surgical outcomes of patients undergoing surgery for CRE were retrospectively reviewed. Risk factors of postoperative morbidity were analyzed using univariate and multivariate analysis. Survival and reoperation rates for CRE were evaluated. RESULTS: Among the 404 patients included, 351 patients (86.88%) received resectional surgery, whereas the remaining patients received conservative procedures. No differences were detected between patients with resection and those without resection with regard to major morbidity (P = 0.486) and surgical complications (P = 0.715). Laparoscopy resulted in a shorter postoperative hospital stay (P = 0.035). After multivariate analysis, history of hypertension (odds ratio [OR] = 2.490; P = 0.046), previous acute radiation enteritis (OR = 1.832; P = 0.033), intraoperative blood loss of more than 200 mL (OR = 2.235; P = 0.006), and thrombocytopenia (OR = 2.544; P = 0.016) were determined as independent predictors of postoperative major morbidity. During follow-up, 22 patients required reoperation for CRE recurrence, and the reoperation rate was significantly lower in patients receiving resectional surgery (P = 0.005). CONCLUSIONS: Resection is feasible for CRE with acceptable postoperative morbidity and lower reoperation rate. Correction of preoperative thrombocytopenia, minimizing intraoperative blood loss, and close monitoring of hypertensive patients and those with history of acute radiation enteritis are critical to reduce postoperative complications.


Assuntos
Enterite/cirurgia , Complicações Pós-Operatórias/epidemiologia , Lesões por Radiação/cirurgia , Adulto , Idoso , China/epidemiologia , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/radioterapia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
15.
BMC Gastroenterol ; 16: 12, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26822147

RESUMO

BACKGROUND: Fundamental researches suggest that ileum presents greater adaptive potential than the jejunum. However, few studies estimate the association between ileum and adaptive potential in human. To discover the association, we conducted this matched case-control study. METHODS: A 1:2 pair-matched, case-control study was conducted from January 1, 2001 to January 1, 2015 in Intestinal Rehabilition and Transplant Center. The case group was ileum predominated (IP) group and the control group was jejunum predominated (JP) group. Demographic data, medical history and progression of each patient were collected. RESULTS: There were 24 IP cases and 48 JP controls in this study. The cumulative probabilities of parenteral nutrition (PN) weaning in IP group were higher than that in JP group. The Bristol stool scale scores of IP group were lower than that of JP group at third month. The Cox proportional hazards regression model confirmed that IP had a higher odds of PN weaning (OR = 2.69; 95 % CI: 1.27, 5.70, p = 0.01) as compared with JP group. The conditional logistic regression with 1:2 matching also confirmed IP group had a higher odds (OR = 4.84; 95 % CI: 2.02, 11.56, p <0.01). CONCLUSIONS: Our results indicated that ileum presents greater adaptive potential than the jejunum in nutrition and fluid absorption. And a potential anatomic subtype of short bowel syndrome was proposed. Further research need to be conducted to more fully understand the adaptive potential of ileum besides nutrition and fluid absorption.


Assuntos
Adaptação Fisiológica/fisiologia , Íleo/fisiopatologia , Jejuno/fisiopatologia , Nutrição Parenteral/estatística & dados numéricos , Síndrome do Intestino Curto/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome do Intestino Curto/classificação , Síndrome do Intestino Curto/terapia , Desmame
16.
Nutr J ; 15(1): 57, 2016 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-27233356

RESUMO

BACKGROUND: Chronic radiation enteritis (CRE) is defined as loss of absorptive capacity after irradiation due to chronic inflammation and damage of intestinal mucosa, which may lead to varying degrees of malnutrition. The aim of this study was to evaluate the potential correlation between the nutritional status and systemic inflammation in patients with CRE. METHODS: Medical records of 92 patients with CRE and 184 age- and sex-matched controls in a single center from January 2010 to October 2015 were retrospectively reviewed. All enrolled subjects underwent nutritional status analysis, including three different nutritional indices: Nutritional Risk Screening-2002 (NRS-2002), Patient-generated Subjective Global Assessment (PG-SGA) and Controlling Nutritional Status (CONUT), bioelectrical impedance spectroscopy (BIS), and biochemical markers, within 24 h of admission. RESULTS: The results showed that NRS-2002, PG-SGA and CONUT were all positively correlated with neutrophil/lymphocyte ratio (NLR) (r = 0.304, 0.384 and 0.425, all p < 0.001) and C-reactive protein (CRP) (r = 0.357, 0.479 and 0.230, all p < 0.001), while negatively correlated with albumin (r = -0.612, -0.727 and -0.792, all p < 0.001) and total cholesterol (TC) (r = -0.485, -0.545 and -0.473, all p < 0.001) in patients with CRE, respectively. Body cell mass (BCM) has been deemed a key body composition parameter. It was positively correlated with albumin (r = 0.489, p < 0.001) and TC (r = 0.237, p < 0.001), while negatively correlated with NLR (r = -0.140, p = 0.02) and CRP (r = -0.215, p < 0.001). A multivariate linear regression analysis showed that values of intracellular water (ß coefficient = 0.760, p < 0.001), extracellular water (ß coefficient = 0.006, p = 0.011), protein (ß coefficient = 0.235, p < 0.001) and CRP (ß coefficient = 0.001, p = 0.009) were independent determinants of BCM. CONCLUSION: This study revealed that BIS combined with nutritional assessments and biochemical markers were appropriate methods to assess the nutritional and inflammatory status in patients with CRE. Furthermore, the nutritional status was verified to be significantly correlated with systemic inflammation.


Assuntos
Biomarcadores/sangue , Composição Corporal , Enterite/sangue , Desnutrição/sangue , Avaliação Nutricional , Radioterapia/efeitos adversos , Adulto , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Colesterol/sangue , Doença Crônica , Creatinina/sangue , Impedância Elétrica , Enterite/complicações , Feminino , Humanos , Inflamação , Modelos Lineares , Linfócitos/citologia , Masculino , Desnutrição/etiologia , Pessoa de Meia-Idade , Análise Multivariada , Neutrófilos/citologia , Estado Nutricional , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/metabolismo
17.
Artif Organs ; 40(8): 738-45, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27097758

RESUMO

The effect of normothermic extracorporeal membrane oxygenation (NECMO) on small bowel preservation in a clinically relevant large animal model of expected donation after cardiac death (eDCD) was evaluated. Thirty domestic crossbred donor pigs were divided into five groups. The first group served as the live donation (LD) group, the second group served as the donation after cardiac death (DCD) group, and the remaining were further assigned into three subgroups: E1 group (1 h NECMO support), E3 group (3 h NECMO support), and E5 group (5 h NECMO support). Pathology, electron microscopy, energy metabolism, cell apoptosis, and tight junction (TJ) protein expression level of intestinal mucosa and the level of plasma d-lactic acid were evaluated in normal, cardiac death and at the end of extracorporeal support, respectively. The mean arterial pressure and PaO2 were maintained over 60 and 267 mm Hg during NECMO support, respectively. One hour of extracorporeal support could improve the energy status in intestines of the DCD group. Although the histologic damage and apoptosis of the E1 group had no significant difference with those of the LD and DCD groups (P > 0.05), the levels of intestinal mucosa TJ protein decreased (P < 0.05), and plasma d-lactic acid increased progressively (P < 0.05). With the extension of extracorporeal support, the degree of intestinal mucosa damage and intestinal permeability gradually increased, as well as the content of adenosine triphosphate in intestinal mucosa. The normothermic extracorporeal support for 1 h in DCD is beneficial for improving the energy status and viability of the bowel. However, the integrity of intestinal mucosa was destroyed gradually as extracorporeal support time went by. And the activation of intestinal epithelial apoptosis and hyperoxia might be the factors that lead to intestinal mucosa injury.


Assuntos
Oxigenação por Membrana Extracorpórea , Parada Cardíaca/patologia , Parada Cardíaca/terapia , Intestinos/patologia , Trifosfato de Adenosina/análise , Animais , Apoptose , Temperatura Corporal , Modelos Animais de Doenças , Metabolismo Energético , Feminino , Parada Cardíaca/sangue , Parada Cardíaca/metabolismo , Ácido Láctico/sangue , Masculino , Ocludina/análise , Suínos , Proteína da Zônula de Oclusão-1/análise
18.
J Surg Res ; 194(2): 415-419, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25499692

RESUMO

BACKGROUND: The aim of this study was to determine the safety and feasibility of laparoscopic surgery for radiation enteritis-induced intestinal stenosis requiring ileocecal resection. METHODS: Clinical records of radiation enteritis patients that underwent laparoscopic ileocecal resection and ileo-ascending colonic side-to-side anastomosis in a single center from January 2012-February 2014 were retrospectively analyzed. Thirty patients were identified and matched by abdominal adhesion grade, age, gender, primary malignancy distribution, previous abdominal surgery history, and body mass index to 30 patients that underwent open surgery for the same procedure from August 2009-December 2011. General information, operative findings, and short-term outcomes were compared between the two groups. RESULTS: The conversion rate of laparoscopic surgery was 23.3%. The length of skin incision in the laparoscopic group was significantly shorter than that of the open surgery group (6.8 cm versus 15.8 cm, P = 0.001). Laparoscopic surgery significantly decreased recovery time to total enteral nutrition (10.3 d versus 15.6 d, P = 0.037); however, postoperative hospital stay was not significantly different between the two groups (28.2 d versus 32.4 d, P = 0.924). Intraoperative blood loss (125 mL versus 189 mL, P = 0.000) and operation time (138 min versus 171 min, P = 0.003) were significantly improved in the laparoscopic group compared with those in the open surgery group. Laparoscopic surgery did not significantly decrease postoperative morbidity but did decrease the pleural effusion rate. CONCLUSIONS: Laparoscopic surgery is feasible for treatment of radiation enteritis-induced intestinal stenosis with a relatively low conversion rate. Laparoscopic surgery is as safe as open surgery and is superior to open surgery with decreased skin incision length, operation time, intraoperative blood loss, and postoperative recovery time to total enteral nutrition.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Enterite/cirurgia , Complicações Intraoperatórias/epidemiologia , Laparoscopia/estatística & dados numéricos , Lesões por Radiação/cirurgia , Adulto , Idoso , China/epidemiologia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Estudos de Viabilidade , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
19.
Clin Lab ; 61(3-4): 371-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25975005

RESUMO

BACKGROUND: Chemotherapy-induced mucosal barrier dysfunction is of clinical interest. However, the assessment of mucosal barrier dysfunction still poses challenges. In this study, we compared several biomarkers with the dual sugar gut permeability test for assessing mucosal barrier dysfunction during chemotherapy. METHODS: Forty-two patients with gastric or colorectal cancer underwent chemotherapy, including FAM or FOLFOX4 regimens. Patients were asked to grade and record their symptoms of gastrointestinal toxicity daily. The urinary lactulose-mannitol ratio was measured to assess the intestinal permeability. Plasma levels of citrulline, diamine oxidase (DAO), D-lactic acid, and endotoxin were also measured. Intestinal permeability was observed in the subgroup of patients with diarrhea or constipation. RESULTS: The urinary lactulose-mannitol ratio and plasma citrulline levels increased on the third and sixth post-chemotherapy days, respectively. There were no significant differences in the plasma levels of D-lactic acid, endotoxin or DAO activity compared to their levels before chemotherapy. The urinary lactulose-mannitol ratio in diarrhea patients was significantly higher than in constipation patients. CONCLUSIONS: These results indicate that the urinary lactulose-mannitol ratio and plasma citrulline level are appropriate biomarkers for assessing mucosal barrier dysfunction in patients receiving chemotherapy. Mucosal barrier dysfunction in diarrhea patients was greater than in constipation patients.


Assuntos
Antineoplásicos/efeitos adversos , Biomarcadores/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/complicações , Mucosa Intestinal/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/complicações , Adulto , Idoso , Amina Oxidase (contendo Cobre)/sangue , Citrulina/sangue , Neoplasias Colorretais/tratamento farmacológico , Endotoxinas/metabolismo , Feminino , Humanos , Absorção Intestinal , Mucosa Intestinal/metabolismo , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Permeabilidade , Neoplasias Gástricas/tratamento farmacológico , Fatores de Tempo
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