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1.
Int J Med Sci ; 17(17): 2751-2762, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162803

RESUMO

Background: To date, the effect of vasopressin on organ damages after acute mesenteric ischemia (MI) remains poorly understood. Aims: To investigate the effect of terlipressin, a selective vasopressin V1 receptor agonist, versus norepinephrine on the intestinal and renal injuries after acute MI, and to explore the underlying mechanism of terlipressin. Methods: Acute MI model was produced by clamping the superior mesenteric artery for 1 hour. Immediately after unclamping, terlipressin or norepinephrine was intravenously administered for 2 hours. Meanwhile, in vitro, RAW264.7 cells were treated with lipopolysaccharide or lipopolysaccharide+terlipressin. In addition, wortmannin was used to determine the role of phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway in the potential impacts of terlipressin. Results: MI led to severe hypotension, caused notable intestinal and renal impairments and resulted in high mortality, which were markedly improved by terlipressin or norepinephrine. Terlipressin increased mean arterial pressure, decreased intestinal epithelial cell apoptosis, inhibited the generation of M1 macrophage in intestinal and renal tissues, and hindered the release of inflammatory cytokines after MI. Moreover, in cultured macrophages, terlipressin reduced the mRNA level of specific M1 markers and the release of inflammatory cytokines caused by lipopolysaccharide challenge. Wortmannin decreased the expression of PI3K and Akt induced by terlipressin in cells and in tissues, and abolished the above protective effects conferred by terlipressin. Conclusions: Terlipressin or norepinephrine could effectively improve organ damages and mortality after acute MI. Terlipressin elevates blood pressure and inhibits intestinal epithelial apoptosis and macrophage M1 polarization via the PI3K/Akt pathway.

2.
Ann Transl Med ; 8(12): 785, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32647710

RESUMO

Background: Transesophageal echocardiography (TEE) performed by intensivists is increasingly used in critically ill patients. However, TEE is usually not the preferred monitoring tool, especially when transthoracic echocardiography (TTE) appears to have addressed the clinical problems. As a result, it remains largely unknown whether TEE is a clinically valuable replacement or supplement for TTE as a primary tool in evaluating haemodynamic problems in critically ill surgical patients. The purpose of this study was to assess the diagnostic and therapeutic value of TEE instead or in addition to TTE in critically ill surgical patients with hemodynamic instability. Methods: A prospective observational study was conducted. A total of 68 consecutive patients were enrolled from December 2016 to February 2018. TEE was routinely performed in addition to TTE, and the imaging data from TTE and TEE were successively disclosed to two different primary physicians, who reported any resulting changes in management. The two physicians were required to reach a consensus if there was any disagreement. The results of the additional TEE examination were compared with the clinical findings and TTE information. The image quality of TTE views was classified as a good (score 2), suboptimal (score 1) or poor view (score 0). According to the scores of TTE images, the patients were divided into two groups: patients with adequate TTE views (score ≥6) and inadequate TTE views (score <6). Results: The results of additional TEE examination were classified into four categories. TEE failed to provide additional information about the initial diagnosis and therapy (class 1) in 26 patients (38.2%). Of the remaining 42 patients (61.8%), TEE instead or in addition to TTE revealed new findings or led to significant changes in therapy, as TTE supplied inadequate information. TEE used in addition to TTE led to a new diagnosis without therapeutic implications (class 2) in 11 patients (16.2%) and made a major clinical contribution leading to a therapeutic change (class 3) in 23 patients (33.8%). TEE used instead of TTE determined the diagnosis and therapy in 8 patients (11.8%) whose haemodynamic problems could not be addressed by TTE (class 4). In total, TEE had critical therapeutic benefits (class 3 and 4) that was not provided by TTE in 31 patients (45.6%). Of particular concern was that TEE had a higher proportion of therapeutic benefits to patients with inadequate TTE views than those with adequate TTE views (54.3% vs. 27.3%, P=0.036). Conclusions: TEE as a feasible clinical tool is useful for critically ill surgical patients with hemodynamic instability, especially for the patients with inadequate TTE views. TEE instead or in addition to TTE could provide valuable information for diagnosis, which may bring significant therapeutic benefits.

3.
Infect Drug Resist ; 13: 2053-2061, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636658

RESUMO

Purpose: Although immune dysfunction has been investigated in adult septic patients, early immune status remains unclear. In this study, our primary aim was to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality. Patients and Methods: A post hoc analysis of a multicenter, randomized controlled trial was conducted; 273 patients whose immune status was evaluated within 48 hours after onset of sepsis were enrolled. Early immune status was evaluated by the percentage of monocyte human leukocyte antigen-DR (mHLA-DR) in total monocytes within 48 hours after onset of sepsis and it was classified as immunoparalysis (mHLA-DR ≤30%) or non-immunoparalysis (>30%). Three logistic regression models were conducted to explore the associations between early immunoparalysis and hospital mortality. We also developed two sensitivity analyses to find out whether the definition of early immune status (24 hours vs 48 hours after onset of sepsis) and immunotherapy affect the primary outcome. Results: Of the 181 elderly (≥60yrs) and 92 non-elderly (<60yrs) septic patients, 71 (39.2%) and 25 (27.2%) died in hospital, respectively. The percentage of early immunoparalysis in the elderly was twice of that in the non-elderly patients (32% vs 16%, p=0.006). For the elderly, hospital mortality was higher in the immunoparalysis ones than the non-immunoparalysis ones (53.4% vs 32.5%, p=0.009). But there was no significant difference in hospital mortality between immunoparalysis non-elderly patients and non-immunoparalysis non-elderly ones (33.5% vs 26.0%, p=0.541). By means of logistic regression models, we found that early immunoparalysis was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status and immunotherapy did not affect the outcomes. Conclusion: The elderly were more susceptible to early immunoparalysis after onset of sepsis. Early immunoparalysis was independently associated with poor prognosis in elderly, but not in non-elderly patients.

5.
J Thorac Dis ; 12(4): 1632-1634, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32395303
6.
J Infect Dis ; 221(Supplement_2): S164-S173, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32176783

RESUMO

BACKGROUND: Information on possible donor-derived transmission events in China is limited. We evaluated the impacts of liver transplantation from infected deceased-donors, analyzed possible donor-derived bacterial or fungal infection events in recipients, and evaluated the etiologic agents' characteristics and cases outcomes. METHODS: A single-center observational study was performed from January 2015 to March 2017 to retrospectively collect data from deceased-donors diagnosed with infection. Clinical data were recorded for each culture-positive donor and the matched liver recipient. The microorganisms were isolated and identified, and antibiotic sensitivity testing was performed. The pathogens distribution and incidence of possible donor-derived infection (P-DDI) events were analyzed and evaluated. RESULTS: Information from 211 donors was collected. Of these, 82 donors were infected and classified as the donation after brain death category. Overall, 149 and 138 pathogens were isolated from 82 infected donors and 82 matched liver recipients, respectively. Gram-positive bacteria, Gram-negative bacteria, and fungi accounted for 42.3% (63 of 149), 46.3% (69 of 149), and 11.4% (17 of 149) of pathogens in infected donors. The incidence of multidrug-resistant bacteria was high and Acinetobacter baumannii was the most concerning species. Infections occurred within the first 2 weeks after liver transplantation with an organ from an infected donor. Compared with the noninfection recipient group, the infection recipient group experienced a longer mechanical ventilation time (P = .004) and intensive care unit stay (P = .003), a higher incidence of renal dysfunction (P = .026) and renal replacement therapy (P = .001), and higher hospital mortality (P = .015). Possible donor-derived infection was observed in 14.6% of cases. Recipients with acute-on-chronic liver failure were more prone to have P-DDI than recipients with other diseases (P = .007; odds ratio = 0.114; 95% confidence interval, .025-.529). CONCLUSIONS: When a liver recipient receives a graft from an infected deceased-donor, the postoperative incidence of infection is high and the infection interval is short. In addition, when a possible donor-derived, drug-resistant bacterial infection occurs, recipients may have serious complications and poor outcomes.

7.
Intensive Care Med ; 44(11): 1816-1825, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29971593

RESUMO

PURPOSE: Recent clinical data suggest that terlipressin, a vasopressin analogue, may be more beneficial in septic shock patients than catecholamines. However, terlipressin's effect on mortality is unknown. We set out to ascertain the efficacy and safety of continuous terlipressin infusion compared with norepinephrine (NE) in patients with septic shock. METHODS: In this multicentre, randomised, double-blinded trial, patients with septic shock recruited from 21 intensive care units in 11 provinces of China were randomised (1:1) to receive either terlipressin (20-160 µg/h with maximum infusion rate of 4 mg/day) or NE (4-30 µg/min) before open-label vasopressors. The primary endpoint was mortality 28 days after the start of infusion. Primary efficacy endpoint analysis and safety analysis were performed on the data from a modified intention-to-treat population. RESULTS: Between 1 January 2013 and 28 February 2016, 617 patients were randomised (312 to the terlipressin group, 305 to the NE group). The modified intention-to-treat population comprised 526 (85.3%) patients (260 in the terlipressin group and 266 in the NE group). There was no significant difference in 28-day mortality rate between the terlipressin group (40%) and the NE group (38%) (odds ratio 0.93 [95% CI 0.55-1.56]; p = 0.80). Change in SOFA score on day 7 was similar between the two groups: - 7 (IQR - 11 to 3) in the terlipressin group and - 6 (IQR - 10 to 5) in the NE group. There was no difference between the groups in the number of days alive and free of vasopressors. Overall, serious adverse events were more common in the terlipressin group than in the NE group (30% vs 12%; p < 0.001). CONCLUSIONS: In this multicentre, randomised, double-blinded trial, we observed no difference in mortality between terlipressin and NE infusion in patients with septic shock. Patients in the terlipressin group had a higher number of serious adverse events. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov: ID NCT01697410.


Assuntos
Cuidados Críticos , Norepinefrina/uso terapêutico , Choque Séptico/terapia , Terlipressina/uso terapêutico , Vasoconstritores/uso terapêutico , Adulto , Idoso , China , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Choque Séptico/mortalidade , Taxa de Sobrevida , Resultado do Tratamento
8.
J Trauma Acute Care Surg ; 85(3): 580-587, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29847538

RESUMO

BACKGROUND: To investigate the effect of biliary tract external drainage (BTED) on inflammatory mediators and pathomorphism of intestine, liver, and lung in septic rats. METHOD: 48 SD rats (n = 8 per group) were randomized into six groups: control, sepsis, sepsis plus BTED, normal bile (obtained from eight healthy rats), and septic bile infusion for 6 hours respectively to test the effects of BTED bile infusion on cytokines' expression and tissue injury in the intestine, liver, and lung of septic/normal rats. Co-cultivation of intestinal epithelial cells (IEC-6) with bile for 12 hours was performed to evaluate the potential cytotoxicity of septic bile. Survival rate for sepsis plus BTED rats was detected compared with sepsis without BTED group (n = 20 per group) at 24, 48, and 72 hours, respectively. RESULTS: BTED for 6 hours significantly reduced the mRNA expression levels of tumor necrosis factor alpha (TNF-α) and IL-1ß (all p < 0.05 vs. sepsis group), whereas mRNA expression of TNF-α and IL-1ß in the intestine was increased after 6 hours' septic bile infusion compared with normal bile infusion group (all p < 0.05). TNF-α concentration in septic bile was significantly higher than that in the control group (p < 0.001). Tissue injury was significantly attenuated after 6 hours' BTED. CONCLUSIONS: BTED can significantly restrain the mRNA expression of TNF-α and IL-1ß in the intestine, liver, and lung and attenuate histological damage in septic rats.


Assuntos
Bile/metabolismo , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Drenagem/métodos , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Sepse/metabolismo , Animais , Bile/fisiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/genética , Intestinos/fisiopatologia , Intestinos/cirurgia , Fígado/fisiopatologia , Pulmão/fisiopatologia , Masculino , Insuficiência de Múltiplos Órgãos/genética , Insuficiência de Múltiplos Órgãos/patologia , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley/genética , Sepse/patologia , Sepse/cirurgia , Fator de Necrose Tumoral alfa/genética
9.
Mol Med Rep ; 18(2): 1524-1530, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29845275

RESUMO

Autophagy, part of the innate immune defense mechanisms, is activated during the initial phase of septic insult. Previous studies indicated that micro (mi)RNAs are additionally involved in the host response to sepsis; however, the association between miRNAs and autophagy during this process is not fully understood. To study the role of miRNA (miR)­23a in autophagy initiated by sepsis, macrophages treated with lipopolysaccharides, in addition to blood samples from patients, were evaluated for miR­23a expression levels. Cell viability, inflammatory mediators and autophagic markers were investigated following overexpression or inhibition of miR­23a. The results suggested that miR­23a was suppressed subsequent to septic insult, promoting autophagy and suppressing a hyper inflammatory response, leading to enhanced cell viability. A luciferase assay and western blot analysis confirmed ubiquitin­like protein ATG12 to be the target of miR­23a. The present study revealed that the downregulation of miR­23a regulates an inflammatory response during septic insult via autophagy promotion.


Assuntos
Proteína 12 Relacionada à Autofagia/genética , Autofagia/genética , MicroRNAs/genética , Sepse/genética , Idoso , Animais , Antagomirs/genética , Antagomirs/metabolismo , Proteína 12 Relacionada à Autofagia/imunologia , Sequência de Bases , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica , Genes Reporter , Humanos , Lipopolissacarídeos/farmacologia , Luciferases/genética , Luciferases/metabolismo , Masculino , Camundongos , MicroRNAs/antagonistas & inibidores , MicroRNAs/imunologia , Pessoa de Meia-Idade , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Células RAW 264.7 , Sepse/imunologia , Sepse/patologia , Transdução de Sinais
10.
Chin Med J (Engl) ; 131(3): 253-261, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29363638

RESUMO

BACKGROUND: Passive leg raising (PLR) represents a "self-volume expansion (VE)" that could predict fluid responsiveness, but the influence of systolic cardiac function on PLR has seldom been reported. This study aimed to investigate whether systolic cardiac function, estimated by the global ejection fraction (GEF) from transpulmonary-thermodilution, could influence the diagnostic value of PLR. METHODS: This prospective, observational study was carried out in the surgical Intensive Care Unit of the First Affiliated Hospital of Sun Yat-sen University from December 2013 to July 2015. Seventy-eight mechanically ventilated patients considered for VE were prospectively included and divided into a low-GEF (<20%) and a near-normal-GEF (≥20%) group. Within each group, baseline hemodynamics, after PLR and after VE (250 ml 5% albumin over 30 min), were recorded. PLR-induced hemodynamic changes (PLR-Δ) were calculated. Fluid responders were defined by a 15% increase of stroke volume (SV) after VE. RESULTS: Twenty-five out of 38 patients were responders in the GEF <20% group, compared to 26 out of 40 patients in the GEF ≥20% group. The thresholds of PLR-ΔSV and PLR-Δ cardiac output (PLR-ΔCO) for predicting fluid responsiveness were higher in the GEF ≥20% group than in the GEF <20% group (ΔSV: 12% vs. 8%; ΔCO: 7% vs. 6%), with increased sensitivity (ΔSV: 92% vs. 92%; ΔCO: 81% vs. 80%) and specificity (ΔSV: 86% vs. 70%; ΔCO: 86% vs. 77%), respectively. PLR-Δ heart rate could predict fluid responsiveness in the GEF ≥20% group with a threshold value of -5% (sensitivity 65%, specificity 93%) but could not in the GEF <20% group. The pressure index changes were poor predictors. CONCLUSIONS: In the critically ill patients on mechanical ventilation, the diagnostic value of PLR for predicting fluid responsiveness depends on cardiac systolic function. Thus, cardiac systolic function must be considered when using PLR. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-OCH-13004027; http://www.chictr.org.cn/showproj.aspx?proj=5540.


Assuntos
Débito Cardíaco/fisiologia , Hidratação , Coração/fisiopatologia , Hipovolemia/diagnóstico , Posicionamento do Paciente , Sístole , Adulto , Idoso , Feminino , Hemodinâmica , Humanos , Hipovolemia/fisiopatologia , Unidades de Terapia Intensiva , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Estudos Prospectivos , Respiração Artificial , Volume Sistólico
11.
Intensive Crit Care Nurs ; 45: 85-90, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29158024

RESUMO

OBJECTIVE: To prepare the Simplified Therapeutic Intervention Scoring System (TISS-28) to measure nursing workload in Intensive Care Units in Guangdong Province of China. METHODS: A non-experimental descriptive study was conducted in the intensive care units in the Province. TISS-28, TISS-76, Acute Physiology and Chronic Health Evaluation (APACHE II) were all measured. RESULTS: There were significant positive correlations between TISS-28 and APACHE II (n=91, r=0.432, p<0.001), TISS-76 scores (n=83, r=0.764, p<0.001). A significant difference was found between the mean TISS-28 score in the first day of the intensive care stay and the last day (30.76±6.86 vs 24.67±5.48, p<0.001). A significant intra-class correlation was found between TISS-28 scores collected by the researcher and research associates (ICC=0.959, p<0.001). CONCLUSION: The reliability and validity of TISS-28 were shown in Chinese intensive care units. It is a practical tool for estimating the nursing workload and providing opportunities to compare the data between intensive care units in different facilities. The TISS-28 Chinese version is recommended to guide the allocation of nursing manpower in Chinese intensive care units.


Assuntos
Estado Terminal/enfermagem , Psicometria/instrumentação , Psicometria/métodos , Terapêutica/classificação , APACHE , Adulto , Idoso , China , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Terapêutica/normas , Tradução , Carga de Trabalho/estatística & dados numéricos
12.
Crit Care Med ; 45(12): e1218-e1225, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28902121

RESUMO

OBJECTIVES: Data about the critical care resources in China remain scarce. The purpose of this study was to investigate the variation and distribution of critical care resources in Guangdong province from 2005 to 2015. DESIGN: Data in regard to critical care resources were collected through questionnaires and visits every 5 years from 2005. SETTING: All hospitals in Guangdong province were screened and hospitals that provide critical care services were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: One hundred eleven, 158, and 284 hospitals that provide critical care services were enrolled in the three consecutive surveys respectively. The number of ICUs, ICU beds, intensivists, and nurses increased to 324, 3,956, 2,470, and 7,695, respectively, by 2015. Adjusted by population, the number of ICU beds per 100,000 (100,000) population increased by 147.7% from 2005 to 2015, and the number of intensivists and nurses per 100,000 population increased by 35.3% and 55.1% from 2011 to 2015. However, the numbers in the Pearl River Delta, a richer area, were higher than those in the non-Pearl River Delta area (ICU beds: 4.64 vs 2.58; intensivists: 2.90 vs 1.61; nurses: 9.30 vs 4.71 in 2015). In terms of staff training, only 17.85% of intensivists and 14.29% of nurses have completed a formal accredited critical care training program by 2015. CONCLUSIONS: Our study was the first one to investigate the trend and distribution of critical care resources in China. The quantity of ICU beds and staff has been increasing rapidly, but professional training for staff was inadequate. The distribution of critical care resources was unbalanced. Our study can be beneficial for healthcare policymaking and the allocation of critical care resources in Guangdong province and other provinces in China.


Assuntos
Cuidados Críticos/estatística & dados numéricos , Unidades de Terapia Intensiva/provisão & distribução , China , Equipamentos e Provisões/provisão & distribução , Produto Interno Bruto , Número de Leitos em Hospital/estatística & dados numéricos , Humanos , Recursos Humanos em Hospital/provisão & distribução
13.
Exp Ther Med ; 14(1): 260-266, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28672923

RESUMO

Intestinal ischemia/reperfusion (I/R) injury is associated with a high morbidity and mortality. Vasopressin is administered to critically ill patients with potential intestinal I/R. However, the impacts of vasopressin on intestinal epithelia under ischemic/anoxic conditions remain unclear. The aim of the present study was to evaluate the effects of terlipressin, a highly selective vasopressin V1 receptor agonist, on oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced damage in intestinal epithelial cells (IEC-6). IEC-6 cells were subjected to OGD for 4 h, followed by 4 h re-oxygenation. Terlipressin was incubated with cells for 4 h following OGD. Following OGD/R, IEC-6 cell viability, proliferation and apoptosis, as well as cell cycle dynamics, were assessed and the levels of tumor necrosis factor (TNF)-α and 15-F2t-isoprostane in the culture medium were measured. In addition, wortmannin, a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, was administrated to investigate the mechanism of terlipressin action. The results demonstrated that IEC-6 cell viability and proliferation decreased, and cell apoptosis increased, following OGD/R. However, IEC-6 cell cycle dynamics did not significantly change 4 h after OGD. Incubation with 25 nM terlipressin significantly improved cell viability, proliferation and apoptosis. Furthermore, terlipressin inhibited the secretion of TNF-α and 15-F2t-isoprostane from IEC-6 cells following OGD/R. The aforementioned effects of terlipressin were completely abolished following the application of 2 µM wortmannin. Therefore, the current study demonstrated that terlipressin administration following OGD attenuates OGD/R-induced cell damage via the PI3K signaling pathway. These results may help physicians to better understand and more effectively use terlipressin in a clinical setting.

15.
Biomed Pharmacother ; 91: 476-484, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28478272

RESUMO

Hypoxia inducible factor-1α (HIF-1α) plays an essential role in hypoxia and inflammatory response. Oxygen metabolic dysfunction and cascade amplification of inflammatory response are prominent pathophysiological characteristics in sepsis induced acute lung injury (ALI). In this study, we started with septic mesenteric lymph injection model to investigate whether HIF-1α played a role in the pathogenesis of ALI induced by septic lymph. The data demonstrated that rats injected with septic lymph showed a significant higher Lung Injury Scale and MPO(myeloperoxidase) levels than that of rats injected with normal saline/lymph. ALI was associated with a higher degree of HIF-1α expression in the lungs infused by septic lymph. Intratracheal delivery of YC-1(3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole) significantly attenuated lung inflammatory damages. Furthermore, in vitro studies, human alveolar type II epithelial cell (A549)/human pulmonary microvascular endothelial cell (HPMEC) incubated by septic lymph showed dramatically decreased cell viability, higher levels of inflammatory cytokines (TNF-α, IL-6 and IL-1ß) and excitation of HIF-1α expression (Immunofluorescence localization/RT-PCR test) simultaneously. Nevertheless, compared with the non-silencing cell lines, A549/HPMEC with HIF-1α gene silencing manifested increased viability and restrained cytokines' expression after incubation with septic lymph. These results indicate that HIF-1α expression can be induced and activated in rats during the acute lung inflammatory damages triggered by septic lymph injection and that lung inflammatory injuries occur via a HIF-1α-dependent pathway.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lesão Pulmonar/metabolismo , Pulmão/patologia , Linfa/metabolismo , Pneumonia/metabolismo , Sepse/metabolismo , Células A549 , Animais , Sobrevivência Celular , Citocinas/metabolismo , Células Endoteliais/metabolismo , Inativação Gênica , Humanos , Indazóis/farmacologia , Indazóis/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Masculino , Artérias Mesentéricas , Peroxidase/metabolismo , Ratos Sprague-Dawley , Sepse/tratamento farmacológico
16.
Chin Med J (Engl) ; 129(24): 2967-2973, 2016 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-27958229

RESUMO

BACKGROUND: Sepsis is the leading cause of death among critically ill patients. Herein, we conducted a national survey to provide data on epidemiology and treatment of sepsis in the clinical practice in China, which has no detailed epidemiological data available on sepsis. METHODS: This was a prospective cross-sectional survey from December 1, 2015 to January 31, 2016 in all provinces/municipalities of the mainland of China. The primary outcome of this study was the incidence of sepsis, and the secondary outcome was its etiology in China. Patients with sepsis admitted to the Intensive Care Units were included in this study. The demographic, physiological, bacteriological, and therapeutic data of these patients were recorded. The incidence of sepsis was estimated using the data from the sixth census in China, reported by the Chinese National Health and Family Planning Commission and the National Bureau of Statistics as the standard population. The independent risk factors for increased mortality from sepsis were calculated. CONCLUSIONS: This study indicated the incidence and outcome of sepsis in China. It also showed the most common etiology of different sites and types of infection, which could guide empiric antibiotic therapy. Moreover, it provided information on the independent risk factors for increased mortality due to sepsis. The findings provide evidence to guide clinical management and may help improve the outcome in septic patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02448472; https://clinicaltrials.gov/show/NCT02448472.


Assuntos
Sepse/epidemiologia , China/epidemiologia , Estudos Transversais , Estudos Epidemiológicos , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Estudos Prospectivos , Sepse/etiologia
17.
Ther Clin Risk Manag ; 12: 1481-1486, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27729796

RESUMO

PURPOSE: To evaluate the clinical effects of magnesium sulfate in the treatment of diffuse axonal injury (DAI). PATIENTS AND METHODS: This study was a randomized, double-blind, placebo-controlled trial conducted in the First Affiliated Hospital of Sun Yat-sen University, Guangzhou and Zhuhai People's Hospital, Zhuhai, two trauma center hospitals. A total of 128 patients suffered from DAI, with initial Glasgow coma scale (GCS) scores of 3-8. They were randomly divided into two groups: magnesium sulfate treatment (MST) group (n=64) and control group (n=64). The MST group received 250 µmol/kg magnesium sulfate intravenously 20 minutes after admission, followed by 750 µmol/kg magnesium sulfate intravenously daily for 5 days. The control group received standard management without MST. GCS scores and serum neuron-specific enolase values were measured and recorded at admission, and on days 3 and 7 after injury. Outcomes were determined by Glasgow outcome scale scores at discharge and at 3 months' follow-up, respectively. RESULTS: After the 7-day treatment, patients in the MST group, compared with those in the control group, had a lower serum neuron-specific enolase level (25.40±6.66 vs 29.58±7.32, respectively, P=0.001) and higher GCS score (8.23±2.72 vs 7.05±2.64, respectively, P=0.016). Although the length of stay and mortality did not differ between the groups in the intensive care unit, Glasgow outcome scale score was significantly lower in the MST group at discharge (3.30±1.35 vs 3.90±1.10, P=0.004) and 3 months after discharge (2.95±1.48 vs 3.66±1.44, P=0.009). CONCLUSION: Early treatment with magnesium sulfate resulted in a significant improvement in DAI outcome. Further studies are needed to confirm the clinical significance of treatment of DAI patients with magnesium sulfate.

18.
Chin Med J (Engl) ; 129(14): 1719-24, 2016 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-27411461

RESUMO

BACKGROUND: An acute respiratory distress syndrome (ARDS) is still one of the major challenges in critically ill patients. This study aimed to investigate the effect of inhibiting c-Jun N-terminal kinase (JNK) on ARDS in a lipopolysaccharide (LPS)-induced ARDS rat model. METHODS: Thirty-six rats were randomized into three groups: control, LPS, and LPS + JNK inhibitor. Rats were sacrificed 8 h after LPS treatment. The lung edema was observed by measuring the wet-to-dry weight (W/D) ratio of the lung. The severity of pulmonary inflammation was observed by measuring myeloperoxidase (MPO) activity of lung tissue. Moreover, the neutrophils in bronchoalveolar lavage fluid (BALF) were counted to observe the airway inflammation. In addition, lung collagen accumulation was quantified by Sircol Collagen Assay. At the same time, the pulmonary histologic examination was performed, and lung injury score was achieved in all three groups. RESULTS: MPO activity in lung tissue was found increased in rats treated with LPS comparing with that in control (1.26 ± 0.15 U in LPS vs. 0.77 ± 0.27 U in control, P < 0.05). Inhibiting JNK attenuated LPS-induced MPO activity upregulation (0.52 ± 0.12 U in LPS + JNK inhibitor vs. 1.26 ± 0.15 U in LPS, P < 0.05). Neutrophils in BALF were also found to be increased with LPS treatment, and inhibiting JNK attenuated LPS-induced neutrophils increase in BALF (255.0 ± 164.4 in LPS vs. 53 (44.5-103) in control vs. 127.0 ± 44.3 in LPS + JNK inhibitor, P < 0.05). At the same time, the lung injury score showed a reduction in LPS + JNK inhibitor group comparing with that in LPS group (13.42 ± 4.82 vs. 7.00 ± 1.83, P = 0.001). However, the lung W/D ratio and the collagen in BALF did not show any differences between LPS and LPS + JNK inhibitor group. CONCLUSIONS: Inhibiting JNK alleviated LPS-induced acute lung inflammation and had no effects on pulmonary edema and fibrosis. JNK inhibitor might be a potential therapeutic medication in ARDS, in the context of reducing lung inflammatory.


Assuntos
Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/toxicidade , /tratamento farmacológico , Animais , Antracenos/uso terapêutico , Colágeno/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Ratos , Transdução de Sinais/efeitos dos fármacos
19.
Int J Clin Exp Med ; 8(5): 7351-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26221275

RESUMO

Klotho is a potential biomarker and therapeutic target in a model of acute kidney injury (AKI) induced in rats by ischemia-reperfusion injury. However, the sensitivity and specificity of serum Klotho for early detecting clinical AKI are unknown. This prospective study evaluated the significance of serum Klotho for early detection of postoperative AKI among adult patients undergoing cardiac valve replacement surgery. Moreover, we also compared the utilities of serum Klotho, serum creatinine and cystatin C in early detection of AKI. There was no marked difference between AKI and non-AKI groups in preoperative serum Klotho levels. Immediately after the operation, serum Klotho decreased significantly in patients with AKl. In spite of the poor specificity, its diagnostic sensitivity was excellent. On postoperative 1 d, with the rapid recovery toward the preoperative level, the ability of serum Klotho for early detecting AKI declined. Changes in serum Klotho levels at every time point among patients without AKI did not reveal any statistical significance. We showed that AKI is a state of transient Klotho deficiency in patients undergoing cardiac valve replacement surgery. Serum Klotho levels were drastically decreased beginning at 0h with ideal ROC-AUC, sensitivity but poor specificity, which didn't exceed 4 h after operation, suggesting that serum Klotho could serve as a potential biomarker for CSA-AKI, especially during the short period after cardiac surgery. A larger multicentre cohort study of population in different ages undergoing on-pump cardiac surgery is required to identify the optimal timing of serum Klotho measurement and the optimal cut-off points for clinical use to further refine the optimal timing for early detection of AKI.

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