To investigate the effects of pyruvate (Pyr) on adenosine triphosphate (ATP), endothelial nitric oxide synthase (eNOS), and nitric oxide (NO) in red blood cells (RBCs) during the cardiopulmonary bypass procedure (CPB), blood, 500 mL, was collected from each of 10 healthy dogs (weight 12–18 kg). The blood was divided into two parts (250 mL each) and randomly assigned into the control group (Group C, n = 10) or the Pyr group (Group P, n = 10). The blood was commingled with an equal volume of 0.9% NaCl and pyruvated isotonic solution (Pyr 50 mM) in the extracorporeal circuit in the two groups, respectively. The CPB procedure was fixed at 120 min, and the transferring flow was 4 L/min. Contents of ATP in RBCs, eNOS activities, and NO productions in plasma were measured before CPB and during CPB at 30, 60, 90, and 120 min in both groups. The ATP level, eNOS activity, and NO production were not different prior to CPB between the two groups. A decline of ATP levels was shown in both groups but remained significantly higher in Group P than in Group C at the same time points during in vitro CPB (P < 0.01). Values of eNOS and NO were significantly increased in Group C but markedly reduced in Group P during CPB, compared with pre‐CPB (P < 0.01). The CPB procedure significantly damaged dogs’ RBCs in the ATP level, eNOS activity, and NO production, in vitro, but Pyr effectively protected RBCs in these functions during CPB. Pyr would be clinically protective for RBCs during CPB.
Background Stress response always occurs in cardiac valve replacement patients undergoing cardiopulmonary bypass (CPB). Methods 60 patients undergoing cardiac valve replacement were recruited and randomized into control and Dex groups. Dex group received 1.0 μg·kg-1 of Dex for 10 min intravenously before anesthesia, followed by 0.5 μg·kg-1·h-1 of Dex, steadily administered throughout the procedure. And controlled group received the identical velocity of saline as Dex group. Plasma level of cortisol (Cor), epinephrine (E), norepinephrine (NE), and serotonin (5-HT) were evaluated at four timepoints: Before administration (T0), sawn sternum (T1), end of extracorporeal circulation (T2), and 24 h post operation (T3). General data of operation and recovery such as heart rate (HR), mean arterial pressure (MAP), intraoperative bispectral index (BIS), and hospitalization time in the intensive care unit (ICU) were also compared. Results Increase of Cor, E, NE, and 5-HT for the Dex group was significant lesser than that in the control group (P < 0.05), and ICU hospitalization time and ventilator support time was significantly shorter in the Dex group. The proportion of patients discharged from the hospital with better prognosis was significantly higher than that in the control group, while there were no significant differences in hospitalization costs and vasoactive drugs use between the two groups. Conclusions Dex reduces plasma Cor, E and NE elevations in patients after CPB, alleviates the stress reaction of the body, shortens the hospitalization time and ventilator support time in ICU, and plays a positive role in the rehabilitation of patients undergoing cardiac valve replacement. Trial registration China Clinical Trial Registry (No. ChiCTR-IPR-17010954) March 22rd, 2017.
Platinum‐based chemotherapy promotes drug resistance in ovarian cancer. We investigated the antichemoresistance characteristics of diallyl trisulfide (DATS) in cisplatin‐resistant ovarian cancer cells, in vitro and in vivo. Previous preclinical studies have revealed that DATS regulates distinct hallmark cancer‐signaling pathways. The cell cycle pathway is the most investigated signaling pathway in DATS. Additionally, post‐DATS treatment has been found to promote proapoptotic capacity through the regulation of intrinsic and extrinsic apoptotic pathway components. In the present study, we found that treating cisplatin‐sensitive and cisplatin‐resistant ovarian cell lines with DATS inhibited their proliferation and reduced their IC50. It induced cell apoptosis and promoted oxidative phosphorylation through the regulation of the AMPK/SIRT1/PGC1α pathway, OXPHOS, and enhanced chemotherapy sensitivity. DATS treatment alleviated glutamine consumption in cisplatin‐resistant cells. Our findings highlight the role of DATS in overcoming drug resistance in ovarian cancer in vitro and in vivo. In addition, we elucidated the role of the AMPK/SIRT1/PGC1α signaling pathway as a potential target for the treatment of drug‐resistant ovarian cancer.
Background: The study aimed to investigate the protective effects and regulatory mechanism of sevoflurane postconditioning (SPC) in pulmonary apoptosis induced by cardiopulmonary bypass (CPB). Methods: Twenty-four healthy dogs were divided into control (C group), ischemia/reperfusion (I/R group), sevoflurane postconditioning (SPO group) and wortmannin group (S+W group). At 10 min after the establishment of CPB, the left pulmonary artery was blocked. 2% sevoflurane was administrated when the pulmonary artery was reopened. Wortmannin was delivered for 10 min before the pulmonary artery was open. Before thoracotomy was implemented (T1), when the artery was reopened (T2) and 2 h after CPB (T3), blood and inferior lobe of left lung were isolated and subjected to gas analysis, pathological examination, western blot, and TUNEL staining. Results: No obvious changes were observed in C group throughout the experiment. The conditions of all treated groups progressively deteriorated and no difference could be found except the number of apoptotic cells of T3 between S+W and I/R group. At T2, the treated groups showed similar conditions. At T3, the lung function and structure of S group were improved than I/R and S+W group. S group showed the highest p-Akt expression, the lowest cleaved-caspase 3 expression and apoptotic cell percentage.Conclusions: Ischemia reperfusion of lung during CPB reduces lung function and injures the pulmonary structure via inducing lung apoptosis. Sevoflurane postconditioning preserves lung function and structure by alleviating apoptosis via activation of PI3K/Akt.
Aims: The study aimed to investigate the protective effects and regulatory mechanism of sevoflurane postconditioning (SPC) in pulmonary apoptosis induced by cardiopulmonary bypass (CPB). Methods: Twenty-four healthy dogs were divided into a control (C group), ischemia/reperfusion (I/R group), sevoflurane postconditioning (S group), and wortmannin group (S+W group). At 10 min after the establishment of CPB, the left pulmonary artery was blocked. When the pulmonary artery was reopened, 2% sevoflurane was administered. Wortmannin was delivered 10 min before the pulmonary artery was open. Before thoracotomy was implemented (T1), when the artery was reopened (T2) and 2 h after CPB (T3), blood and the inferior lobe of the left lung were isolated and subjected to gas analysis, pathological examination, western blot, and TUNEL staining. Results: No obvious changes were observed in the C group throughout the experiment. The conditions of all treated groups progressively deteriorated, and no difference could be found except in the number of apoptotic cells of T3 between the S+W and I/R groups. At T2, the treated groups showed similar conditions. At T3, the lung function and structure of the S group were improved in I/R and S+W groups. The S group showed the highest p-Akt expression, the lowest cleaved-caspase 3 expression, and apoptotic cell percentage. Conclusions: Ischemia-reperfusion of the lung during CPB reduces lung function and injures the pulmonary structure via inducing lung apoptosis. Sevoflurane postconditioning preserves lung function and structure by alleviating apoptosis via activation of PI3K/Akt.
Background Methicillin-resistant Staphylococcus aureus (MRSA) can cause invasive infections with significant mortality in neonates. This study aimed to analyze the clinical characteristics and antibiotic resistance profiles of invasive MRSA infections and determine risk factors associated with invasive MRSA infections in newborn inpatients. Methods This multicenter retrospective study of inpatients from eleven hospitals in the Infectious Diseases Surveillance of Pediatrics (ISPED) group of China was performed over a two-year period (2018–2019). Statistical significance was calculated by applying the χ2 test or by Fisher’s exact test in the case of small sample sizes. Results A total 220 patients were included. Among included cases, 67 (30.45%) were invasive MRSA infections, including two deaths (2.99%), while 153 (69.55%) were noninvasive infections. The invasive infections of MRSA occurred at a median age of 8 days on admission, which was significantly younger compared to 19 days in noninvasive cases. Sepsis (86.6%) was the most common invasive infection, followed by pneumonia (7.4%), bone and joint infections (3.0%), central nervous system infection (1.5%), and peritonitis (1.5%). Congenital heart disease, low birth weight infant (<2500 g), but not preterm neonates, and bronchopulmonary dysplasia, were more commonly found in invasive MRSA infections. All these isolates were susceptible to vancomycin and linezolid and were resistant to penicillin. Additionally, 69.37% were resistant to erythromycin, 57.66% to clindamycin, 7.04% to levofloxacin, 4.62% to sulfamethoxazole-trimethoprim, 4.29% to minocycline, 1.33% to gentamicin, and 3.13% were intermediate to rifampin. Conclusion Low age at admission (≤8 days), congenital heart disease, and low birth weight were associated with invasive MRSA infections in neonates, and no isolates resistant to vancomycin and linezolid were found. Determining these risks in suspected neonates may help identify patients with imminent invasive infections who may require intensive monitoring and therapy.
IntroductionMethicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health worldwide. In December 2015, the Infectious Disease Surveillance of Pediatrics (ISPED) program was organized to monitor bacterial epidemiology and resistance trends in children.MethodsThis retrospective study was conducted from January 2016–December 2021 on patients at eleven ISPED-group hospitals.ResultsFrom 2016–2021, a total of 13024 MRSA isolates were obtained from children. The most common age group for patients with MRSA infection was less than 3 years old, and newborns were an important group affected by MRSA infection. MRSA was most commonly isolated from the lower respiratory, an abscess, a secretion, or blood in neonates and from the lower respiratory, an abscess, or the upper respiratory in non-neonates. All isolates were susceptible to vancomycin and linezolid and resistant to penicillin; additionally, 76.88%, 54.97%, 22.30%, 5.67%, 5.14%, 3.63%, and 1.42% were resistant to erythromycin, clindamycin, tetracycline, levofloxacin, sulfamethoxazole-trimethoprim (TMP-SMX), gentamicin, and rifampin, respectively. Between 2016 and 2021, a significant increase was seen in the levofloxacin- and TMP-SMX-resistance rates (from 5.45% to 7.14% and from 4.67% to 6.50%, respectively) among MRSA isolates, along with a significant decrease in the rates of resistance to erythromycin (from 82.61% to 68.08%), clindamycin (from 60.95% to 46.82%), tetracycline (from 25.37% to 17.13%), gentamicin (from 4.53% to 2.82%), and rifampin (from 1.89% to 0.41%).DiscussionThe antibiotic-resistance rates varied among MRSA isolated from different sources. Because of the high antibiotic resistance rate to clindamycin, this antibiotic is not recommended for empirical treatment of MRSA infections, especially in osteomyelitis.
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