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BACKGROUND: The aim of this study was to investigate the prognostic role of platelet to albumin ratio (PAR) and in persistent acute kidney injury (pAKI) of patients admitted to the intensive care unit (ICU). METHODS: We involved pAKI patients from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and eICU Collaborative Research Database (eICU-CRD). Receiver operating curve (ROC) analysis was performed to evaluate the optimal cut-off PAR. RESULTS: A total of 7,646 patients were finally included in the present study. The optimal cut-off value of PAR was 7.2. The high-PAR group was associated with pAKI (hazard ratio [HR]: 3.25, 95% CI: 2.85-3.72, P < 0.001). We also performed this in the validation cohort, the results further confirmed that the high-PAR group was associated with pAKI (HR: 2.24, 95% CI: 1.86-2.71, P < 0.001). The PAR exhibited good pAKI predictive abilities in the original cohort (C-index: 0.726, 95%CI: 0.714-0.739) and in the validation cohort (C-index: 0.744, 95%CI:0.722-0.766) Moreover, as a systemic inflammatory indicator, PAR depicted better predictive ability compared to other systemic inflammatory indicators. CONCLUSION: The present study manifested that elevated PAR could predicts pAKI in patients admitted to ICU. PAR may be an easily obtained and useful biomarker to clinicians for the early identification of pAKI.
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Injúria Renal Aguda , Albuminas , Contagem de Plaquetas , Humanos , Injúria Renal Aguda/diagnóstico , Biomarcadores , Unidades de Terapia Intensiva , Prognóstico , Estudos Retrospectivos , Curva ROCRESUMO
BACKGROUND: Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the progression of sepsis-induced acute kidney injury (AKI). In this study, we aimed to explore the functions of lncRNA cancer susceptibility candidate 2 (CASC2) in sepsis-induced AKI. METHODS: The sepsis cell models were established by exposing HK2 and HEK293 cells into lipopolysaccharide (LPS). Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to determine the expression of CASC2, miR-545-3p and peroxisome proliferator-activated receptor-α (PPARA) mRNA. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis and wound healing assay were employed for cell viability, apoptosis and migration, respectively. Western blot assay was conducted for the protein levels of E-cadherin, α-SMA and PPARA. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by specific kits. The relationship between miR-545-3p and CASC2 or PPARA was verified by dual-luciferase reporter assay. RESULTS: CASC2 level was decreased in sepsis patients' serums and LPS-treated HK2 and HEK293 cells. CASC2 overexpression facilitated cell viability and restrained cell apoptosis, migration, epithelial-mesenchymal transition (EMT) and oxidative stress in LPS-triggered HK2 and HEK293 cells. CASC2 was identified as a sponge for miR-545-3p to regulate PPARA expression. MiR-545-3p overexpression restored the impact of CASC2 on LPS-induced injury in HK2 and HEK293 cells. Moreover, miR-545-3p overexpression aggravated LPS-induced cell injury in HK2 and HEK293 cells by targeting PPARA. CONCLUSION: CASC2 overexpression relieved the damage of HK2 and HEK293 cells mediated by LPS treatment through regulating miR-545-3p/PPARA axis.
Assuntos
Injúria Renal Aguda/metabolismo , MicroRNAs/metabolismo , PPAR alfa/metabolismo , Sepse/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Sepse/complicações , Adulto JovemRESUMO
Ferroptosis is characterized by the accumulation of iron-derived reactive oxygen species (ROS). Ferroptosis causes neuronal death in multiple neurological disorders. Dexmedetomidine (Dex), an extensively used anesthetic, has neuroprotective effects against ROS, but its effect on iron metabolism remains unknown. In this study, SK-N-SH cells were treated with Dex for 24 h before treatment with 100 µM tert-butyl hydroperoxide (t-BHP; an ROS inducer) for 1 h. Afterward, intracellular ROS and labile ferrous iron [Fe(II)] levels were assessed. Dex hindered the increase in cellular ROS and labile Fe(II) levels caused by t-BHP, although Dex alone had no effect on labile Fe(II) level. t-BHP increased the expression of iron importers, transferrin receptor-1 and divalent metal transporter-1, and iron regulatory protein 1 and 2. These effects were abrogated by Dex treatment and SP-1 knockdown. t-BHP increased the phosphorylation of c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 4 (STAT4), the primary up-stream activators of SP-1, but Dex decreased this. This study, for the first time, revealed that the antioxidative effect of Dex is partly associated to the inhibition of intracellular iron accumulation induced by t-BHP. Dex regulates iron metabolism by regulating iron importers and exporters through JNK/Sp1 and Stat4/Sp1 signaling. It is worth investigating whether Dex can protect neurons from ferroptosis.
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Dexmedetomidina/farmacologia , Ferro/metabolismo , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT4/metabolismo , Fator de Transcrição Sp1/metabolismo , terc-Butil Hidroperóxido/farmacologia , terc-Butil Hidroperóxido/toxicidadeRESUMO
Hypoxic-ischemic brain damage (HIBD) frequently induces cognitive impairments. Investigating the role of sevoflurane postconditioning (SPC) in HIBD, we conducted experiments involving HIBD modeling, SPC treatment, and interventions with the PERK inhibitor GSK2656157 or the PERK activator CCT020312, administered 30 min before modeling, followed by SPC treatment. Behavioral testing using the Morris water maze test and Neurological Deficiency Scale (NDS) was conducted. Additionally, Nissl staining assessed hippocampal CA1 area neuronal density, TUNEL staining evaluated hippocampal CA1 area neuronal apoptosis, and Western blot determined hippocampal CA1 area protein levels, including Bax, Bcl-2, p-PERK/PERK, p-eIF2/eIF2, ATF4, CHOP, GRP78, Bax, and Bcl-2 protein levels. Following SPC treatment, HIBD rats exhibited improved spatial learning and memory abilities, reduced neuronal apoptosis, increased neuronal density in the hippocampal CA1 area, elevated Bcl-2 protein level, decreased Bax protein levels, and decreased levels of endoplasmic reticulum stress pathway related proteins (p-PERK/PERK, p-eIF2/eIF2, ATF4, CHOP and GRP78). Pre-modeling treatment with the PERK inhibitor treatment improved outcomes in HIBD rats. However, pre-modeling treatment with the PERK activator CCT020312 counteracted the protective effects of SPC against HIBD in rats. In conclusion, SPC alleviates neuronal apoptosis in the hippocampus CA1 area of HIBD rats by inhibiting the endoplasmic reticulum stress pathway PERK/ATF4/CHOP, thereby mitigating HIBD in rats.
Assuntos
Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Hipóxia-Isquemia Encefálica , Sevoflurano , Animais , Ratos , Apoptose , Proteína X Associada a bcl-2/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 2 em Eucariotos/farmacologia , Hipocampo/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Sevoflurano/farmacologiaRESUMO
BACKGROUND: Lymphocyte to monocyte ratio (LMR) has been long implicated in the prediction of many inflammatory-related diseases. However, the possible value as prognostic marker of LMR have not been evaluated in cardiogenic shock (CS) patients. The aim of the study was to assess the relationship between LMR on admission and in-hospital mortality in CS patients. METHODS: Data on patients diagnosed with CS were extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. We performed a single-institution, retrospective study of 1487 CS patients and determined the optimal cut-off for LMR by X-tile software. Propensity score matching (PSM) and inverse probabilities of treatment weighting (IPTW) were conducted to control confounders. Cox proportional hazards model was performed to evaluate the relationship between LMR and in-hospital mortality. Kaplan-Meier curves and receiver operating characteristics (ROC) analysis were applied to assess the prognostic value of LMR. RESULTS: The optimal cut-off value for LMR was 0.9. Cox proportional hazards model demonstrated that lower LMR (< 0.9) was independently associated with in-hospital mortality with hazard ratio (HR) of 1.40 (1.12-1.74, P = 0.003). The results were consistent with survival analyses (P < 0.001, Log rank test). Adding LMR< 0.9 to the sequential organ failure assessment (SOFA) score improved discrimination and risk stratification for in-hospital mortality. CONCLUSION: Lower level of LMR is related to higher risk of in-hospital mortality of patients with CS. As an easily available biomarker, LMR can independently predict the in-hospital mortality in CS patients.
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OBJECTIVE: To investigate the changes of serum leptin, lipid levels, adiponectin, NO and TNF-α in patients withnon-traumatic ischemic necrosis of the femoral head of the femoral head and its meanings. METHODS: A total of 80 patients with ischemic necrosis of the femoral head were selected from January 2015 to January 2016. And 30 healthy volunteers who took the same time were selected as the control group. Both subjects were given venous blood in the morning fasting. Serum leptin levels were measured by radioimmunoassay. Serum lipids, high and low density lipoprotein, cholesterol, triglyceride and apolipoprotein A1 were detected by automatic biochemical analyzer. Apolipoprotein B was measured by radioimmunoassay. The levels of serum adiponectin were measured by radioimmunoassay. The levels of NO and TNF-α in serum were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the control group, the levels of cholesterol, triglyceride level, middle and low density lipoprotein and apolipoprotein B were significantly increased in INFH serum; the levels of high density lipoprotein and apolipoprotein A1 were significantly decreased The contents of NO and TNF-α were significantly increased, the content of adiponectin was significantly decreased. There was significant difference between the two groups (Pâ¯<â¯.05). CONCLUSION: The levels of serum cholesterol, triglyceride level, low density lipoprotein level, apolipoprotein B level, leptin, NO and TNF-α levels in serum of INHF patients were positively correlated with the condition of INHF patients, and high density lipoprotein levels, Apolipoprotein A1 levels and adiponectin levels were negatively correlated with INHF patients.
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This study is to constitute a composite skin substitute with epidermal stem cells (ESCs) and fibroblasts on collagen sponge. ESCs were selected by rapid attachment to collagen IV for 10 min. Collagen was extracted from rat's tail. The matrix lattice was fabricated by freeze-dryer and cross-linked with glutaraldehyde. Fibroblasts were inoculated on collagen sponge and cultured for 1 week prior to inoculation of ESCs. Having cultured for 2 weeks in submerged culture, the bioengineered tissue was raised to the air-liquid interface and cultured for 2 weeks. The artificial skin was then grafted onto full skin loss wounds of nude mice. Collagen sponge membrane lacking cell inoculation and an artificial skin with epidermal cells (ECs) and fibroblasts were used as controls. The wounds were observed daily. Tissue samples were harvested and examined by means of histology, immunohistochemistry and electron microscopy. The wounds in the test group healed at a significantly faster rate than controls, with good skin appearance and minimal scar formation. The control group showed delayed wound healing and intensive wound contraction as compared to the test group. Thus the skin substitute with ESCs seemed to be a good equivalent.
Assuntos
Queimaduras/cirurgia , Células Epiteliais/transplante , Transplante de Células-Tronco/métodos , Animais , Colágeno , Fibroblastos/transplante , Imuno-Histoquímica , Camundongos , Camundongos Nus , Transplante de Pele , Pele ArtificialRESUMO
A study of the anatomy and transplantation of the musculus obliquus internus abdominis with a neurovascular pedicle transfer for facial reanimation in one stage is presented. Eleven adult cadavers (22 face sides) were dissected to observe the shape, thickness, innervation, and blood supply of the musculus obliquus internus abdominis. The blood supply of this muscle primarily comes from the musculus obliquus internus abdominis branch of the deep circumflex iliac artery (diameter, 1.3 +/- 0.2 mm), but it can also come from the eleventh intercostal artery (diameter, 1.14 +/- 0.3 mm) and the infracostal artery (diameter, 1.5 +/- 0.2 mm). The branch of the deep circumflex iliac artery and its vena comitans, or the infracostal artery and its vena comitans, could be anastomosed for muscle transplantation. The innervation of the musculus obliquus internus abdominis comes from the tenth and eleventh intercostal nerves (length, 12.7 +/- 1.5 cm) and the infracostal nerve (length, 12.9 +/- 1.3 cm). The eleventh intercostal nerve and the infracostal nerve were selected for anastomosis of muscle transplantation. From November of 1995 to November of 1999, 14 patients with long established facial paralysis were treated with transplantation of a musculus obliquus internus abdominis flap in one stage and were followed for 10 months to 6 years. In 13 patients, the dynamic functions of the transplanted muscles were restored, the obliqueness of the mouth and philtrum while static was corrected, and the facial muscle activities while smiling were harmonized. The eyelids of the paralyzed side could be closed postoperatively, indicating that the function of the orbicularis oculi of the paralyzed side was restored. The single-stage transplantation of a free musculus obliquus internus abdominis flap with one vascular, multi-nerve pedicle is a new method for facial reanimation in the treatment of long established facial paralysis. Because of the simplicity of the procedure and the completeness of the functional reanimation of the paralyzed facial muscles, compared with the results of other free muscle flap transfers, it is an ideal procedure for facial reanimation.
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Paralisia Facial/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/inervação , Músculos Abdominais/irrigação sanguínea , Músculos Abdominais/inervação , Adulto , Cadáver , Expressão Facial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: The majority of vascular anomalies can be diagnosed accurately based on natural history and physical examination; however, there is no convenient, noninvasive, and objective method to (1) differentiate hemangioma from vascular malformation; (2) determine whether a hemangioma is in the proliferating or involuting phase; (3) tell whether or not corticosteroids or interferon alfa-2a is effective for hemangioma; or (4) follow up hemangioma. Although the differences in endothelial cell, protein, and mRNA expression levels of some positive and negative angiogenic factors in the lesions can help to solve these problems, these methods (pathological section, immunohistochemical analysis, and in situ hybridization techniques) necessitate that a biopsy be performed, and the procedures are complicated. A nonsurgical and convenient method would have significant clinical applications. METHODS: Fifty-nine patients with proliferating hemangiomas, 38 with involuting hemangiomas, 18 with vascular malformations, and 12 negative control subjects were examined for serum levels of vascular endothelial growth factor using enzyme-linked immunosorbent assays. RESULTS: The serum level of vascular endothelial growth factor in proliferating hemangiomas was significantly higher than that in involuting hemangiomas, vascular malformations, and negative controls, while differences among involuting hemangiomas, vascular malformations, and negative controls were not statistically significant. In addition, after systemic steroid therapy, the serum level of vascular endothelial growth factor was significantly reduced compared with pretreatment levels in six patients with proliferating hemangiomas. CONCLUSIONS: The serum level of vascular endothelial growth factor may be useful in differentiating hemangioma from vascular malformations, staging hemangiomas, judging the efficacy of steroid therapy, and evaluating follow-up criteria for hemangiomas. The results probably shed new light on the pathogenesis of hemangiomas.
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Vasos Sanguíneos/anormalidades , Hemangioma/diagnóstico , Fator A de Crescimento do Endotélio Vascular/sangue , Capilares/anormalidades , Anormalidades Cardiovasculares/diagnóstico , Pré-Escolar , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Humanos , Lactente , Recém-NascidoRESUMO
OBJECTIVE: Looking for an objective biomedical index to distinguish types and phases of hemangioma in order to provide an objective basis for selecting clinical treatment to hemangioma. METHODS: ELISA (enzyme-linked immunosorbent assay) was used to determine serum VEGF concentration of 15 patients with proliferative hemangioma, 6 with involuted hemangioma, 6 with vascular malformation and 8 infants of the control group. RESULTS: The serum VEGF concentrations of 15 proliferative hemangioma patients were significantly higher than those of involuted hemangioma patients, vascular malformation patients and control group infants. The serum VEGF concentrations of involuted hemangioma patients were a little bit higher than those of vascular malformation patients and control group infants, but without statistic significance. CONCLUSIONS: ELISA could easily and accurately determine the serum VEGF concentration of different types and different phases of hemangioma. The determination of serum VEGF concentration could provide guidance for selecting a protocol of systemic corticosteroid treatment for proliferative hemangioma. Combined with gene expression and distribution of VEGF and its receptors and some other cytokines, the determination of serum VEGF concentration could help elucidate the mechanism of proliferative hemangioma.
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Fatores de Crescimento Endotelial/sangue , Hemangioma/sangue , Linfocinas/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Lactente , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
OBJECTIVE: Despite the causes for melanin increase, the increased gene expression of TYR is a common pathological process. Based on this viewpoint, antisense-S-Oligo of TYR was designed and synthesized to regulate synthesis of melanin in order to explore the treatment for skin pigmentation. METHODS: The cultured melanocytes were divided into 3 groups. The group 1 was treated with endothelin, group 2 treated with ultraviolet ray and group 3 was used as the control. In each group, the 5' antisense-S-Oligo, the 3' antisense-S-Oligo, the mixed antisense-S-Oligo of TYR or Dotap only was added. The melanin content and TYR gene expressions were examined. RESULTS: The 5' antisense-S-Oligo, the 3' antisense-S-Oligo and the mixed antisense-S-Oligo significantly inhibited the increase of melanin content and TYR gene expression, which were caused by endothelin or ultraviolet ray treatment. Of the three treatments, the 3' antisense-S-Oligo showed the strongest effect. CONCLUSION: Antisense-S-Oligo has significant regulating effects on TYR gene expression and melanin content. The 3' antisense-S-Oligo is more effective than the 5' antisense-S-Oligo.