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BACKGROUND: Newly graduated registered nurses leaving the nursing profession in the early stages of their career have enormous financial and time implications for nursing organizations and affect the quality of nursing care. OBJECTIVE: To identify the factors influencing newly graduated registered nurses' intention to leave the nursing profession over the past 10 years. METHODS: The framework developed by Whittemore and Knafl was used to conduct this integrative review. An electronic search was conducted for English articles to identify research studies published between 2011-2022 using the following databases of PubMed, MEDLINE, CINAHL, PsycINFO, and Scopus. Eligible publications were critically reviewed and scored using the Critical Appraisal Skills Program Checklist and the Center for Evidence-Based Management appraisal. RESULTS: Twenty-one studies were analyzed. The main factors affecting newly graduated registered nurses' intention to leave the nursing profession included demographic factors (age, educational level, year of experience, professional title, employment status, health status, shift, hospital location and size), supervisor and peer support, challenges in the workplace, cognitive and affective response to work, work environment (collegial nurse-physician relations, insufficient staffing level, person-work environment fit), gender stereotypes, autonomous motivation, role models, and resilience. CONCLUSIONS: The factors affecting newly graduated registered nurses' intention to leave the nursing profession are multifaceted and should receive continuous attention from nurse managers. The findings provide more comprehensive for nurse administrators to develop intervention strategies to mitigate newly graduated registered nurses' turnover intention.
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With the progression of marine exploration and exploitation, as well as the advancements in mechanical intelligence, the utilization of the unmanned surface vehicle (USV) and the design of their guidance system have become prominent areas of focus. However, the stern ramp recovery of the USV is still in its infancy due to its unique attitude requirements and automation design. Furthermore, few studies have addressed the impact of maritime disturbances, with most research limited to simulations. To enhance the efficiency and accuracy of stern ramp recovery, this paper presents the development and construction of a novel recovery system. By incorporating physical modeling of disturbance forces acting on USVs at sea, the practicality of the system is improved. Additionally, an optimized genetic algorithm is introduced in the navigation module to improve convergence rates and subsequently enhance recovery efficiency. A line-of-sight (LOS) algorithm based on average velocity is proposed in this paper to ensure the attainment of unique attitude requirements and to improve the effectiveness of stern chute recovery. This paper provides a detailed description of the independently designed USV hardware system. Moreover, simulations and practical experiments conducted using this experimental platform are presented, offering a new solution for the USV's stern ramp recovery.
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Alzheimer's disease (AD) has the third highest health expenditures after heart disease and cancer. It has emerged as a serious global health issue. The discovery of new drugs to prevent and treat AD is of utmost importance. Pholidota cantonensis is an edible medicinal plant consumed in China. It is widely used in traditional Chinese medicine to treat various diseases. P. cantonensis has been reported to have antioxidant, anti-inflammatory, antitumor and antibacterial activities. Among these properties, its potent antioxidant activity has attracted our attention, since oxidative stress is one of the important pathological mechanisms involved in AD. This study aimed to isolate the compounds from the active extract and evaluate their bioactivities. Fifteen compounds, including one new compound, were obtained. The isolates were tested for 2,2'-diphenyl-1-picrylhydrazyl (DPPH)/2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities, anti-acetylcholinesterase (anti-AChE) activities and inhibitory effects on nitrogen monoxide (NO) release in the BV-2 cells. Compounds 1, 2, 4, 6, 8, and 13-15 exhibited two kinds of AD-associated bioactivities. More importantly, compound 13 showed more potent NO inhibitory activity (IC50 = 0.72 ± 0.08 µM) than the positive control quercetin (IC50 = 12.94 ± 0.08 µM). Compound 13 also had a higher inhibitory rate (99.59 ± 0.43%) on AChE than that of the positive control galantamine (78.32 ± 1.16%) at the concentrate of 50 µg/mL. Our studies provide new insights into this plant in terms of its potential in the development of new multi-target anti-Alzheimer's disease (anti-AD) drugs.
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Antioxidantes , Pangolins , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , China , Inibidores da Colinesterase/farmacologia , Extratos Vegetais/análise , Extratos Vegetais/farmacologiaRESUMO
OBJECTIVE: This study investigated the effects of high haem oxygenase-1 (HO-1) expression on oxidative injury and the biological behaviours of rat dermal fibroblasts, under high glucose conditions. METHOD: Rat dermal fibroblasts were cultured in normal glucose (1.0g/l), high glucose (4.5g/l) or haemin (5µm). A bilirubin kit, real-time polymerase chain reaction (RT-PCR) and Western blotting measured the protease activity, mRNA, and protein levels of HO-1, respectively. An enzyme-linked immunosorbent assay (ELISA) kit measured media levels of 8-hydroxydeoxyguanosine (8-OHdG), reactive oxygen species (ROS) and collagen (hydroxyproline) secretion. Cell proliferation was measured using flow cytometry. Cell apoptosis was measured using Hoechst 33258 staining and flow cytometry. The transwell method and scratch test evaluated cell migration. RESULTS: HO-1 expression exhibited a time-dependent change that was lowest in the high glucose (HG) group at 96 hours compared with the normal glucose (NG) group. In the HG group, the 8-OHdG, ROS and cell apoptosis were increased, and collagen secretion, cell proliferation and cell migration (horizontal and vertical) were decreased compared with the NG group at 96 hours. Haemin treatment sustained high HO-1 expression for at least 96 hours, and the cells exhibited decreased 8-OHdG and ROS, increased collagen synthesis, improved proliferation and migration ability, and decreased apoptosis in the NG and haemin (NH) group/HG and haemin (HH) group compared with the NG/HG groups. These cells recovered from oxidative injury and biological behaviours dysfunction. CONCLUSION: Haemin induces HO-1 expression in fibroblasts and it may influence the oxidative injury and biological behaviours of fibroblasts. These findings suggest that HO-1 may accelerate the healing of diabetic wounds via alleviation of oxidative injury and improvement of biological behaviours of fibroblasts.
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Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pele/efeitos dos fármacos , Animais , Células Cultivadas/efeitos dos fármacos , Humanos , Modelos Animais , RatosRESUMO
BACKGROUND: Partial hepatectomy is the most definitive treatment for hepatolithiasis. Laparoscopic liver resection, however, presents unique technical challenges. The objectives of this study were to evaluate and compare the safety and perioperative and long-term outcomes of laparoscopic left hemihepatectomy (LLH) versus open left hemihepatectomy (OLH) for left intrahepatic duct stones. METHODS: From March 2009-October 2014, 97 consecutive patients with left intrahepatic duct stones who underwent LLH (n = 46) or OLH (n = 51) were evaluated. We retrospectively reviewed the clinical outcomes and the stone clearance rates of the 97 patients in this study. RESULTS: The median surgical procedure times were 254 min (188-396 min) in the LLH group and 236 min (192-395 min) in the OLH group. No significant difference was found in the surgical procedure times between the two groups. The intraoperative blood loss of the LLH group was less than the OLH group (332 mL [247-914 mL] versus 369 mL [221-996 mL], P = 0.13), but there was no statistical significance. A shorter length of postoperative hospital stay was noticed in laparoscopy group (11 d [8-21 d] versus 12 d [9-24 d], P = 0.01). Postoperative complications were observed in six of the 46 patients (13.0%) after LLH and in 11 of the 51 patients (21.6%) after OLH (P = 0.27). Laparoscopy was comparable with laparotomy in the effectiveness of stone clearance during the first attempt (93.5% versus 94.1%, P = 1.00). CONCLUSIONS: In left-sided hepatolithiasis, LLH was safe and effective: it resulted in low postoperative morbidity, no mortality, and a high stone clearance rate. The potential benefit of LLH was a shorter hospital stay. If consideration is given to the appropriate indication criteria, including the extent of hepatectomy and the location and distribution of lesions, LLH may be an excellent choice for treatment of left-sided hepatolithiasis.
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Hepatectomia/métodos , Litíase/cirurgia , Hepatopatias/cirurgia , Adulto , Idoso , Feminino , Hepatectomia/estatística & dados numéricos , Humanos , Laparoscopia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Laparoscopic surgery for common bile duct stones varies procedurally from a transcystic approach to laparoscopic choledochotomy (LC) with or without biliary drainage. However, LC is a difficult procedure with higher documented morbidity than the transcystic approach. We retrospectively investigated risk factors for adverse outcomes of LC. METHODS: We used logistic regression models to assess 4 categories of adverse outcomes: overall, complications, conversion to open operation and failed surgical clearance. We calculated the area under the receiver operating characteristic curve to evaluate diagnostic accuracy. RESULTS: We included 201 patients who underwent LC in our analysis. Adverse outcomes occurred in 48 (23.9%) patients, complications occurred in 43 (21.4%), retained stones were observed in 8 (4%), and conversion to laparotomy occurred in 7 (3.5%). Multivariate analysis showed that total bilirubin (BIL) and the presence of medical risk factors (MRFs) were significant predictors of adverse outcomes and complications. We calculated the probability of adverse outcomes (p) using the following formula: logit(p) = 0.977 (MRFs) + 0.014 (BIL) - 2.919. p = EXP (logit(p)) ÷ [1+EXP (logit(p))]. According to their logit(p), all patients were divided into a low-risk group (logit(p) ≤ -1.32, n = 130) and a high-risk group (logit(p) > -1.32, n = 71). Patients in the low-risk group had about a 1 in 10 chance (12 of 130) of adverse outcomes developing. Of the 71 patients in the high-risk group, 36 (50.7%) experienced adverse outcomes. CONCLUSION: High BIL and the presence of MRFs could predict adverse outcomes in patients undergoing LC.
CONTEXTE: La chirurgie laparoscopique pour extraction de calculs biliaires logés dans le cholédoque diffère sur le plan technique de la cholédochotomie laparoscopique (CL) par approche transcystique avec ou sans drain biliaire. Toutefois, la CL est une intervention délicate, qui s'accompagne d'un taux de morbidité documenté plus élevé comparativement à l'extraction transcystique. Nous avons analysé rétrospectivement les facteurs de risque à l'égard d'une issue négative de la CL. MÉTHODES: Nous avons utilisé des modèles de régression logistique pour évaluer 4 catégories d'issue négative : issue négative globale, complications, conversion vers une chirurgie ouverte et échec de l'extraction chirurgicale. Nous avons calculé l'aire sous la courbe de la fonction d'efficacité du récepteur pour évaluer la précision diagnostique. RÉSULTANTS: Nous avons inclus dans notre analyse 201 patients soumis à une CL. Une issue négative est survenue chez 48 patients (23,9 %), des complications chez 43 (21,4 %), la persistance des calculs chez 8 (4 %) et la conversion vers la laparotomie chez 7 (3,5 %). L'analyse multivariée a montré que la bilirubine totale (BIL) et la présence de facteurs de risque médicaux (FRM) étaient des prédicteurs significatifs d'une issue négative et de complications. Nous avons calculé la probabilité de survenue d'une issue négative (p) à l'aide de la formule suivante : logit(p) = 0,977 (FRM) + 0,014 (BIL) 2,919. p = EXP (logit(p)) ÷ [1 + EXP (logit(p))]. En fonction de leur valeur logit(p), tous les patients ont été répartis entre un groupe à faible risque (logit(p) ≤ 1,32, n = 130) et un groupe à risque élevé (logit(p) > 1,32, n = 71). Les patients du groupe à faible risque présentaient 1 chance sur 10 (12 sur 130) d'issue défavorable. Parmi les 71 patients du groupe à risque élevé, 36 (50,7 %) ont présenté une issue défavorable. CONCLUSIONS: Un taux de BIL élevé et la présence de FRM pourraient prédire l'issue négative chez des patients soumis à une CL.
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Coledocolitíase/cirurgia , Laparoscopia , Complicações Pós-Operatórias , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bilirrubina/análise , Endoscopia do Sistema Digestório , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/classificação , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: To investigate the incidence and risk factors of hypothermia in patients with acute renal injury (AKI) receiving continuous renal replacement therapy (CRRT), and to compare the effects of different heating methods on the incidence of hypothermia in patients with CRRT. METHODS: A prospective study was conducted. AKI patients with CRRT who were admitted to the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from January 2020 to December 2022 were enrolled as the study subjects. Patients were divided into dialysate heating group and reverse-piped heating group according to randomized numerical table method. Both groups were provided with reasonable treatment mode and parameter setting by the bedside physician according to the patient's specific condition. The dialysis heating group used the AsahiKASEI dialysis machine heating panel to heat the dialysis solution at 37 centigrade. The reverse-piped heating group used the Barkey blood heater from the Prismaflex CRRT system to heat the dialysis solution, and the heating line temperature was set at 41 centigrade. The patient's temperature was then continuously monitored. Hypothermia was defined as a temperature lower than 36 centigrade or a drop of more than 1 centigrade from the basal body temperature. The incidence and duration of hypothermia were compared between the two groups. Binary multivariate Logistic regression analysis was used to explore the influencing factors of hypothermia during CRRT in AKI patients. RESULTS: A total of 73 patients with AKI treated with CRRT were eventually enrolled, including 37 in the dialysate heating group and 36 in the reverse-piped heating group. The incidence of hypothermia in the dialysis heating group was significantly lower than that in the reverse-piped heating group [40.5% (15/37) vs. 69.4% (25/36), P < 0.05], and the hypothermia occurred later than that in the reverse-piped heating group (hours: 5.40±0.92 vs. 3.35±0.92, P < 0.01). Patients were divided into hypothermic and non-hypothermic groups based on the presence or absence of hypothermia, and a univariate analysis of all indicators showed a significant decrease in mean arterial pressure (MAP) in hypothermic patients (n = 40) compared with the non-hypothermic patients [n = 33; mmHg (1 mmHg ≈ 0.133 kPa): 77.45±12.47 vs. 94.42±14.51, P < 0.01], shock, administration of medium and high doses of vasoactive drug (medium dose: 0.2-0.5 µg×kg-1×min-1, high dose: > 0.5 µg×kg-1×min-1) and CRRT treatment were significantly increased [shock: 45.0% (18/40) vs. 6.1% (2/33), administration of medium and high doses of vasoactive drugs: 82.5% (33/40) vs. 18.2% (6/33), administration of CRRT (mL×kg-1×h-1): 51.50±9.38 vs. 38.42±10.97, all P < 0.05], there were also significant differences in CRRT heating types between the two groups [in the hypothermia group, the main heating method was the infusion line heating, which was 62.5% (25/40), while in the non-hypothermia group, the main heating method was the dialysate heating, which was 66.7% (22/33), P < 0.05]. Including the above indicators in a binary multivariate Logistic regression analysis, it was found that shock [odds ratio (OR) = 17.633, 95% confidence interval (95%CI) was 1.487-209.064], mid-to-high-dose vasoactive drug (OR = 24.320, 95%CI was 3.076-192.294), CRRT heating type (reverse-piped heating; OR = 13.316, 95%CI was 1.485-119.377), and CRRT treatment dose (OR = 1.130, 95%CI was 1.020-1.251) were risk factors for hypothermia during CRRT in AKI patients (all P < 0.05), while MAP was protective factor (OR = 0.922, 95%CI was 0.861-0.987, P < 0.05). CONCLUSIONS: AKI patients have a high incidence of hypothermia during CRRT treatment, and the incidence of hypothermia can be effectively reduced by heating CRRT treatment fluids. Shock, use of medium and high doses of vasoactive drug, CRRT heating type, and CRRT treatment dose are risk factors for hypothermia during CRRT in AKI patients, with MAP is a protective factor.
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Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Humanos , Incidência , Estudos Prospectivos , Soluções para DiáliseRESUMO
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer. Neoadjuvant chemotherapy was widely accepted for treating TNBC. This systematic review and meta-analysis aimed to evaluate the efficacy, safety, and survival benefit of platinum-based adjuvant therapy (PBAT) in treating TNBC. The keywords were searched in Medline, Embase, Pubmed, and Cochrane Library database up to July 24, 2022. All the randomized control trials (RCTs) comparing PBAT and non-PBAT in treating TNBC were included in our study. The pathological complete remission (pCR) and complications were compared by odds ratio (OR) and 95% confidence intervals (CIs). The overall survival (OS) and relapse-free survival (RFS) were compared by hazard ratio (HR) and 95% CIs. A total of 19 RCTs were included in our meta-analysis, among which 2,501 patients were treated with PBAT and 2,290 with non-PBAT. The patients treated with PBAT combined a significantly higher pCR rate compared to those patients treated with non-PBAT (49.8% versus 36.4%, OR = 1.27, 95%CI = 1.14-1.43, P < 0.001). Besides, patients treated with PBAT had a significantly better RFS (HR = 0.78, 95%CI = 0.63-0.95, P = 0.016), but not in OS (HR = 0.84, P = 0.304). Although the occurrence of neutropenia and nausea were slightly different between the PBAT group (51.5% and 24.4%) and the non-PBAT group (47.0% and 29.4%), the complications were acceptable in the two treatments groups. Our results demonstrated that TNBC patients treated with PBAT could achieve a higher pCR rate and better RFS benefit without a higher complication rate.Highlights Platinum-based adjuvant therapy provided a higher pCR rate for TNBC.Platinum-based adjuvant therapy prolonged the RFS but without prolongingthe OS.Neutropenia and nausea rate was different between group PBAT and non-PBAT.
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Neutropenia , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Platina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Náusea/tratamento farmacológico , Náusea/etiologia , Neutropenia/tratamento farmacológico , Neutropenia/etiologiaRESUMO
Diabetes have been shown to cause progressive neuronal injury with pain and numbness via advanced glycation end-products (AGEs)-induced neuronal cell apoptosis; however, the valuable drug targets for diabetic neuropathy have been poorly reported so far. In this study, we discovered a natural small-molecule schisandrol A (SolA) with significant protective effect against AGEs-induced neuronal cell apoptosis. ATP6V0D1, a major subunit of vacuolar-type ATPase (V-ATPase) in lysosome was identified as a crucial cellular target of SolA. Moreover, SolA allosterically mediated ATP6V0D1 conformation via targeting a unique cysteine 335 residue to activate V-ATPase-dependent lysosomal acidification. Interestingly, SolA-induced lysosome pH downregulation resulted in a mitochondrial-lysosomal crosstalk by selectively promoting mitochondrial BH3-only protein BIM degradation, thereby preserving mitochondrial homeostasis and neuronal cells survival. Collectively, our findings reveal ATP6V0D1 is a valuable pharmacological target for diabetes-associated neuronal injury via controlling lysosomal acidification, and also provide the first small-molecule template allosterically activating V-ATPase for preventing diabetic neuropathy.
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Neuroinflammation is a fundamental contributor to progressive neuronal damage, which arouses a heightened interest in neurodegenerative disease therapy. Ubiquitin-specific protease 7 (USP7) has a crucial role in regulating protein stability in multiple biological processes; however, the potential role of USP7 in neurodegenerative progression is poorly understood. Here, we discover the natural small molecule eupalinolide B (EB), which targets USP7 to inhibit microglia activation. Cocrystal structure reveals a previously undisclosed covalent allosteric site, Cys576, in a unique noncatalytic HUBL domain. By selectively modifying Cys576, EB allosterically inhibits USP7 to cause a ubiquitination-dependent degradation of Keap1. Keap1 function loss further results in an Nrf2-dependent transcription activation of anti-neuroinflammation genes in microglia. In vivo, pharmacological USP7 inhibition attenuates microglia activation and resultant neuron injury, thereby notably improving behavioral deficits in dementia and Parkinson's disease mouse models. Collectively, our findings provide an attractive future direction for neurodegenerative disease therapy by inhibiting microglia-mediated neuroinflammation by targeting USP7.
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Doenças Neurodegenerativas , Ubiquitina Tiolesterase , Animais , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Bibliotecas de Moléculas Pequenas , Ubiquitina Tiolesterase/genética , Peptidase 7 Específica de Ubiquitina/metabolismoRESUMO
OBJECTIVE: To observe the application effect of high-flow nasal canula oxygen therapy (HFNC) after extubation in patients with mechanical ventilation (MV) in the intensive care unit (ICU). METHODS: A prospective study was conducted. From January 2018 to June 2020, 163 MV patients admitted to Yijishan Hospital of Wannan Medical College were enrolled, and they were divided into HFNC group (82 cases) and traditional oxygen therapy group (81 cases) according to the oxygen therapy model. The patients included in the study were given conventional treatment according to their condition. In the HFNC group, oxygen was inhaled by a nasal high-flow humidification therapy instrument. The gas flow was gradually increased from 35 L/min to 60 L/min according to the patient's tolerance, and the temperature was set at 34-37 centigrade. The fraction of inspiration oxygen (FiO2) was set according to the patient's pulse oxygen saturation (SpO2) and SpO2 was maintained at 0.95-0.98. A disposable oxygen mask or nasal cannula was used to inhale oxygen in the traditional oxygen therapy group, and the oxygen flow was 5-8 L/min, maintaining the patient's SpO2 at 0.95-0.98. The differences in MV duration before extubation, total MV duration, intubation time, reintubation time, extubation failure rate, ICU mortality, ICU stay, and in-hospital stay were compared between the two groups, and weaning failure were analyzed. RESULTS: There was no significant differences in MV duration before extubation (days: 4.33±3.83 vs. 4.15±3.03), tracheal intubation duration (days: 4.34±1.87 vs. 4.20±3.35), ICU mortality [4.9% (4/82) vs. 3.7% (3/81)] and in-hospital stay [days: 28.93 (15.00, 32.00) vs. 27.69 (15.00, 38.00)] between HFNC group and traditional oxygen therapy group (all P > 0.05). The total MV duration in the HFNC group (days: 4.48±2.43 vs. 5.67±3.84) and ICU stay [days: 6.57 (4.00, 7.00) vs. 7.74 (5.00, 9.00)] were significantly shorter than those in the traditional oxygen therapy group, the reintubation duration of the HFNC group was significantly longer than that of the traditional oxygen therapy group (hours: 35.75±10.15 vs. 19.92±13.12), and the weaning failure rate was significantly lower than that of the traditional oxygen therapy group [4.9% (4/82) vs. 16.0% (13/81), all P < 0.05]. Among the reasons for weaning failure traditional oxygen therapy group had lower ability of airway secretion clearance than that of the HFNC group [8.64% (7/81) vs. 0% (0/82), P < 0.05], there was no statistically differences in the morbidity of heart failure, respiratory muscle weakness, hypoxemia, and change of consciousness between the two groups. CONCLUSIONS: For MV patients in the ICU, the sequential application of HFNC after extubation can reduce the rate of weaning failure and the incidence of adverse events, shorten the length of ICU stay.
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Ventilação não Invasiva , Insuficiência Respiratória , Extubação , Cânula , Humanos , Unidades de Terapia Intensiva , Oxigênio , Oxigenoterapia , Estudos Prospectivos , Respiração Artificial , Insuficiência Respiratória/terapiaRESUMO
Several studies have discovered that PI3K/Akt/ mammalian target of rapamycin (mTOR) pathway played an important role in the development of cancer. In this study, we examined the effects of antisense pEGFP-C1-mTOR on cell proliferation, apoptosis and migration of human hepatocellular carcinoma cell lines, HepG2 and SMMC7721 in vitro. We also observed the expression of mTOR and Akt by using RT-PCR and western blot. Our results showed that treatment of cells with antisense pEGFP-C1-mTOR could induce human hepatocellular carcinoma cells' growth inhibition, apoptosis and weaken the migration activity. And we observed that the expression of mTOR was significantly decreased in the cells treated with antisense pEGFP-C1-mTOR and interestingly we discovered that the phosphorylation AKT expression was slightly increased. It indicated that there existed a negative feedback effect which might decrease the therapeutic effects of antisense pEGFP-C1-mTOR. Therefore, we conceive that targeting to inhibit the expression of mTOR in combination with AKT inactivate may increase clinical effectiveness in hepatocellular carcinoma's treatment.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Serina-Treonina Quinases TOR/fisiologia , Antineoplásicos/farmacologia , Elementos Antissenso (Genética) , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Vetores Genéticos , Proteínas de Fluorescência Verde , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Invasividade Neoplásica , Plasmídeos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/efeitos dos fármacos , TransfecçãoRESUMO
PF898 is a strain of Penicillium expansum optimized for the high level production of Penicillium expansum lipase (PEL). This PEL is unique compared with other lipases in several aspects, For example, the PEL shows low sequence identities (<30%) to all other known lipases, and high percentage of hydrophobic residues in the N-terminal region. The PEL was purified to homogeneity and shown to be 28 kDa by SDS-PAGE. Crystals suitable for X-ray diffraction analysis were obtained by the sitting-drop method of vapor diffusion with ammonia sulfate as the precipitating agent at 298 K. The crystals have tetragonal lattice and unit-cell parameters of a=b=88.09 A, c=126.54 A. Diffraction data were collected to a resolution of 2.08 A on an in-house rotating-anode generator.
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Lipase/química , Lipase/isolamento & purificação , Penicillium/enzimologia , Sequência de Aminoácidos , Sequência Conservada , Cristalografia por Raios X , Dados de Sequência Molecular , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , TermodinâmicaRESUMO
The mammalian target of rapamycin (mTOR) is a critical mediator of the phosphoinositide 3-kinase/protein kinase B/mTOR signaling pathway, and mTOR activity is induced following heat shock. Thermotherapy is used to treat hepatocellular carcinoma (HCC). However, the role of mTOR in modulating thermosensitivity in HCC has yet to be elucidated. In the present study, the antisense plasmid pEGFP-C1-mTOR was transfected into SMMC-7721 cells, and the expression levels of mTOR were analyzed by reverse transcription-polymerase chain reaction and western blot analysis. The thermal responses of the transfected cells were also examined. The results revealed that SMMC-7721 cells were sensitive to heat treatment, and cell viability was significantly inhibited following hyperthermia treatment (P<0.01). The mRNA and protein expression levels of mTOR decreased post-transfection. Cell proliferation, colony-forming ability and motility were all significantly decreased following hyperthermia treatment in the transfected cells. Flow cytometry analysis demonstrated that apoptosis was significantly increased following treatment (P<0.01). The number of cells in S phase was increased, and the cell cycle was arrested in S phase. In conclusion, inhibition of mTOR increased the thermosensitivity of SMMC-7721 cells by increasing cellular apoptosis and inducing S phase arrest.
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BACKGROUND: The present study aimed to identify the relationship between glycemic variability (GV) and the 10-y risk of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) patients with good glycemic control. METHODS: Two-hundred forty consecutive T2DM patients (HbA1c≤7.0%) without CVD were included to calculate the 10-y CVD risk by Framingham risk score (FRS), and divided into 3 groups: low-risk group (FRS≤10%), intermediate-risk group (>10%, ≤20%) and high-risk group (>20%). Inter-group differences of GV were determined by comparing the SD of blood glucose (SDBG), mean amplitudes of glycemic excursion (MAGE), and mean of daily differences (MODD) gathered from 72-h continuous glucose monitoring system. RESULTS: The levels of SDBG and MAGE significantly increased along with the raises of 10-y CVD risk of T2DM patients (p<0.01). FRS was positively correlated with age, systolic blood pressure, SDBG and MAGE (r=0.717, 0.525, 0.509 and 0.485 respectively, p<0.01), while negatively correlated with the level of HDL-C (r=-0.348, p<0.01). Furthermore, multivariate logistic regression analysis confirmed that increased MAGE [OR: 1.623(1.198-2.316), p<0.001] and patients with high urine albumin excretion rates [OR: 1.743(1.247-2.793), p<0.001] were independent predictors for high 10-y CVD risk. CONCLUSION: GV predicts independently the 10-y CVD risk of T2DM patients with well-controlled HbA1c.
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Automonitorização da Glicemia , Glicemia/análise , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/análise , Carga Glicêmica , Adulto , Feminino , Índice Glicêmico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
INTRODUCTION: Hepatolithiasis is a prevalent disease in the southeastern coastal regions of China. Partial hepatectomy is the most definitive treatment for hepatolithiasis. This study evaluated the safety and efficacy of the laparoscopic left hemihepatectomy (LLH) for left-sided hepatolithiasis. METHODS: The clinical data of 37 consecutive patients who underwent pure LLH for left-sided hepatolithiasis at Yinzhou Second Hospital between March 2009 and December 2013 were reviewed retrospectively. RESULTS: Pure LLH was performed successfully in 36 patients. Because of severe adhesions from previous choledochotomy, 1 patient was converted to open procedure. The mean operative time was 257.9 minutes (range, 188 to 396 min). The mean duration of postoperative hospital stay was 11.7 days (range, 8 to 21 d). There were 2 (5.4 %) cases of postoperative bile leakage, 2 (5.4%) cases of intra-abdominal fluid collection, and 1 (2.7%) case of incisional infection, which were successfully managed conservatively. Residual stones were observed in 2 (5.4%) patients. The residual stones were located in the common bile duct in these cases and were removed through the T-tube tract by choledochoscopy. During a mean follow-up of 31.3 months (range, 6 to 63 mo), recurrent stones were detected in 2 (5.4%) patients and were successfully treated with endoscopic sphincterotomy. CONCLUSIONS: LLH for left-sided hepatolithiasis is feasible and safe in selected patients.
Assuntos
Ductos Biliares Intra-Hepáticos/cirurgia , Hepatectomia/métodos , Laparoscopia/métodos , Litíase/cirurgia , Hepatopatias/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
There is a low incidence of multiple primary cancer, particularly when the cancer is synchronous. The present report presents a case of synchronous double primary malignancies. A 58-year-old woman was admitted to Ling Nan Hospital (Guangzhou, China) complaining of pain in the left hip. X-ray revealed an osteolytic lesion and further examination indicated the presence of double primary cancer, consisting of hepatic cholangiocarcinoma and thyroid carcinoma. Biopsy of the osteolytic lesion showed a metastatic adenocarcinoma of unknown origin. Subsequently, final diagnosis was confirmed by I-131 scan and liver lesion biopsy. The patient received positive multidisciplinary treatments and survived for 9 months following diagnosis. The results of the present case suggest that multiplicity of primary malignancy is not necessarily an indicator of poor prognosis, as long as effective diagnosis and adequate disease management are achieved.
RESUMO
Visfatin correlates with inflammation and its levels in peripheral blood are associated with some inflammatory diseases. This study aimed to assess the relationship between plasma visfatin levels and conversion of laparoscopic cholecystectomy to open surgery in acute cholecystitis. One hundred and forty-six acute cholecystitis patients and 146 sex- and age-matched healthy controls were recruited and their plasma visfatin levels were determined using an enzyme immunoassay. 17 patients (11.6%) underwent conversion. Plasma visfatin levels were statistically significantly elevated in all patients (97.2±41.8ng/mL), those with (161.4±71.3ng/mL) or without conversion (88.7±26.9ng/mL), compared to controls (40.3±13.3ng/mL, all P<0.001). A linear regression analysis showed that plasma visfatin levels were positively associated with plasma C-reactive protein levels (t=0.510, P<0.001). A logistic-regression analysis showed that age [odds ratio (OR) 1.160, 95% confidence interval (CI) 1.011-1.332, P=0.035] and plasma visfatin levels (OR 1.035, 95% CI 1.005-1.066, P=0.022) appeared to be the independent predictors of conversion. A receiver operating characteristic curve analysis found that plasma visfatin levels predicted conversion with high area under curve (AUC) (AUC, 850; 95% CI, 0.781-0.903). The AUC of the visfatin concentration was similar to that of age (AUC, 0.738; 95% CI, 0.659-0.807) (P=0.188). Visfatin improved the AUC of age to 0.914 (95% CI, 0.856-0.954) (P=0.011) using a combined logistic-regression model. Thus, high plasma levels of visfatin are associated with systemic inflammation, and may independently predict conversion of laparoscopic cholecystectomy to open surgery in acute cholecystitis.
Assuntos
Colecistectomia Laparoscópica , Colecistite Aguda/sangue , Colecistite Aguda/cirurgia , Nicotinamida Fosforribosiltransferase/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROCRESUMO
ßKlotho is a regulator in multiple metabolic processes, while its role in cancer remains unclear. We found the expression of ßKlotho was down-regulated in human hepatocellular carcinoma tissues compared with that in paired adjacent non-tumourous liver tissues. Hepatoma cells also showed decreased expression of ßKlotho compared with normal hepatocyte cells. Reintroduction of ßKlotho into hepatoma cells inhibited their proliferation. The anti-proliferative effect of ßKlotho might be linked with G1 to S phase arrest, which was mediated by Akt/GSK-3ß/cyclin D1 signaling, since forced expression ßKlotho reduced the phosphorylation level of Akt and GSK-3ß and induced down-regulation of cyclin D1. Furthermore, ßKlotho overexpression could inhibit tumorgenesis, while constitutively activated Akt could override the suppressive effects of ßKlotho in vivo. These data suggest ßKlotho suppresses tumor growth in hepatocellular carcinoma.