Search

Clonal haematopoiesis (CH) is an age-associated clonal expansion of blood cells driven by leukaemia-associated somatic mutations. Although CH has been reported to be a risk factor for leukaemia and a number of non-haematopoietic diseases, its role in perioperative medicine remains unexplored. This was a single-centre, prospective, observational study. Patients undergoing radical oesophagectomy were enrolled, and peripheral blood samples were collected for DNA sequencing. Patients with haematopoietic somatic mutations (variant allele frequencies ≥1%) in the DNMT3A gene, TET2 gene, or both were defined as CH carriers. The primary outcome was the incidence of severe postoperative complications (Clavien–Dindo classification ≥3). The secondary outcomes included the major types of postoperative complications, mortality, and other common perioperative variables. Clonal haematopoiesis was found in 21.2% (33/156) of the patients (mean age: 66 yr [range: 26–79 yr]; 83% males). Some 14/33 (42.4%) patients with CH had severe postoperative complications, compared with patients without CH carriers (28 / 123 [22.8%]; P =0.024). Multivariable logistic regression analysis showed that CH was associated with an increased risk of developing severe postoperative complications (odds ratio, 3.63; 95% confidence interval, 1.37–9.66; P =0.010). Among the major postoperative complications, the incidence of pulmonary complications was significantly higher in the patients with CH than in those without CH (15 in 33 [45.5%] vs 30 in 123 [24.4%], P =0.018). Clonal haematopoiesis was associated with a higher incidence of severe postoperative complications in patients undergoing radical oesophagectomy, suggesting that clonal haematopoiesis can play an important role in perioperative medicine. ChiCTR2100044175 (Chinese Clinical Trial Registry, http://www.chictr.org.cn/showproj.aspx?proj=123193). [ABSTRACT FROM AUTHOR]

The present study was designed to compare the intubating conditions of rocuronium giving by "a modified timing principle" in rapid induction and intubation (RSII) with that of the gold standard, succinylcholine. One hundred and twenty-four patients were randomly divided into rocuronium group (group R, n = 62) or succinylcholine group (group S, n = 62). In group R, after rocuronium 0.6 mg kg−1 was given, anaesthesia was induced with propofol 2 mg kg−1 and remifentanil 2 μg kg−1, and tracheal intubation was performed 60 sec after rocuronium administration. In group S, succinylcholine 1.5 mg kg−1 was given after patient lost consciousness induced by the same regimen of group R, and tracheal intubation was performed 60 sec after succinylcholine administration. Our primary endpoint was the intubating conditions. The numbers of patients with excellent and good intubating conditions in group R were 90.0% and 6.7%, respectively, which were comparable with those in group S (91.7% and 5.0% respectively). The apnoea time in group S (79.7 ± 5.1 sec) was longer than that of group R (56.6 ± 4.6 sec) (p = 0.0063). The average BIS values at the time of intubation in group R (64.1 ± 4.1) was higher than that of group S (43.2 ± 5.5) (p = 0.018). In the context of a RSII with lidocaine–remifentanil–propofol, the application of this "modified timing principle" with rocuronium 0.6 mg kg−1 could provide comparable intubating conditions with those achieved by succinylcholine 1.5 mg kg−1. Additionally, this modified timing principle with rocuronium was associated with shorter apnoea time. [ABSTRACT FROM AUTHOR]

In this study, winter wheat G6PDH (TaG6PDH) and 6PGDH (Ta6PGDH) were investigated. Both their expression and their activity were upregulated under cold stress, suggesting that TaG6PDH and Ta6PGDH positively respond to cold stress in winter wheat. Exogenous abscisic acid (ABA) treatment markedly increased the expression and activity levels of TaG6PDH and Ta6PGDH in winter wheat under cold stress. Subsequently, TaG6PDH -and Ta6PGDH were overexpressed in Arabidopsis , and showed stronger reactive oxygen species (ROS)-scavenging ability and higher survival rate compared with wild-type (WT) plants under cold stress. In addition, we found that TaG6PDH and Ta6PGDH overexpression can promote the oxidative pentose phosphate pathway (OPPP) in the cytoplasm and peroxisomes of Arabidopsis. In summary, Arabidopsis overexpressing TaG6PDH and Ta6PGDH showed improved cold tolerance. • TaG6PDH and Ta6PGDH positively respond to cold stress in winter wheat. • Exogenous ABA treatment markedly increased the expression and activity levels of TaG6PDH and Ta6PGDH under cold stress. • In winter wheat, the tillering node is the main wintering organ. • Overexpression of TaG6PDH and Ta6PGDH can enhance cold tolerance in Arabidopsis. [ABSTRACT FROM AUTHOR]

The incidence of pruritus from neuraxial opioids is about 60%. Pruritus causes discomfort and decreases the quality of recovery. This randomized double-blinded clinical trial was aimed to evaluate the prophylactic effects of a single dose IV nalmefene on the incidence and severity of epidural opioid-induced pruritus within 24 h after surgeries. A two-center, randomized, double blinded, controlled clinical trial. The study was conducted from March 2022 to February 2023 at two tertiary care hospitals in China. Patients aged between 18 and 80 years-old who underwent elective surgeries and received epidural analgesia intra- and post-operatively were screened for study enrollment. A total of 306 patients were enrolled, 302 patients underwent randomization and 296 patients were included in the final analysis. The nalmefene group was prophylactically given 0.5 μg/kg nalmefene intravenously while the control group was given the same volume of saline. The primary endpoint was the incidence of pruritus within 24 h after surgeries. The secondary endpoints included time of the first patient-reported pruritus, severity of pruritus after surgeries, severity of acute pain scores after surgeries and other anesthesia/analgesia related side effects. Pruritus occurred in 51 of the 147 (34.69%) patients in the control group and 35 of the 149 (23.49%) patients in the nalmefene group (odds ratio, 0.58; 95% CI, 0.35 to 0.96; P = 0.034) within 24 h postoperatively. Nalmefene group demonstrated delayed onset of pruritus, reduced severity of pruritus and decreased vomiting within 24 h after surgery. There were no significant differences in postoperative analgesia and the incidence of other anesthesia/analgesia associated side effects. A single dose of 0.5 μg/kg nalmefene intravenously significantly reduced the incidence and severity of epidural-opioid induced pruritus within 24 h after surgery without affecting the efficacy of epidural analgesia. Trial registration: Chinese Clinical Trial Registry (www.chictr.org.cn) and the registration number is ChiCTR2100050463. Registered on August 27th, 2021. • Prophylactic IV nalmefene can reduce the incidence of epidural-opioid induced pruritus. • Prophylactic IV nalmefene can attenuate the severity of epidural-opioid induced pruritus. • A single dose IV nalmefene did not affect the analgesic efficacy of epidural local anesthetic and opioid. [ABSTRACT FROM AUTHOR]

Abstract The neurotoxicity of anesthetics on developing brain has been a focused issue for years. However, controversy exists between human and animal studies and surgery may be a potential reason for this. The discovery of glymphatic system, a pathway eliminating soluble substance from central nervous system (CNS), together with recent evidence that surgery-induced Aβ increase contributes to cognition dysfunction made us rethink about the influence of anesthetics on cognitive function. The function of glymphatic system was proved to be enhanced by sleep and sedation, so we assumed that under clinical situation Aβ1-40 whose accumulation played important role in cognitive dysfunction was increased by surgery and eliminated from CNS by glymphatic system. The function of glymphatic system is facilitated by aquaporin-4 (AQP-4), a water channel expressed in highly polarized manor in astrocytic endfeet, whose transcription is regulated by nuclear factor of activated T cells 5 (NFAT5). Our results suggest that under brief operation and sevoflurane exposure, surgery may be the main cause of Aβ increase and sevoflurane increase the elimination of Aβ by up-regulating AQP-4 which is the key component in glymphatic system. [ABSTRACT FROM AUTHOR]

Abstract Aims The development of central nervous system requires proliferation of neural stem cells followed by differentiation. Cell cycle parameters are closely related with cell fate specification and differentiation. Recent researches indicated that wnt/β-catenin signaling pathway might cause proliferation inhibition and differentiation abnormality through interfering NSCs cell cycle. Our previous research also showed that multiple sevoflurane exposure to neural stem cells inhibited proliferation via repressing transcription factor Pax6 and cyclin D1 through inhibiting wnt/β-catenin pathway. All above encouraged us to figure out the effect of sevoflurane on cell cycle and neurogenesis. Main methods Primary mouse cultured neural stem cells were used and exposed to 4.1% sevoflurane for 6 h in this study. The expression of β-catenin, GSK-3β, c-myc and cyclin D1 were determined by western blot and qRT-PCR. FACS was used to measure the cell cycle. The proliferation of NSCs was evaluated by EdU staining while the differentiation was evaluated by Tuj1 and GFAP staining on immunocytochemistry. Key findings We found that exposure to sevoflurane at a concentration of 4.1% for 6 h induced inhibition of wnt/β-catenin pathway, cell cycle arrest at G0/G1 phase and an earlier switch from proliferation to differentiation. GSK-3β specific inhibitor, CHIR99021, attenuated sevoflurane-induced cell cycle arrest and abnormality of neurogenesis in neural stem cells. Significance Our research suggested that sevoflurane arrested cell cycle at G0/G1 phase through inhibition of wnt/β-catenin signaling pathway thus resulting in a premature differentiation in NSCs. This study presents a deeper understanding of the mechanism on cognitive impairment by sevoflurane exposure. [ABSTRACT FROM AUTHOR]

Sevoflurane is widely used in non-obstetric surgeries of pregnant women, but its influences on fetal brain are still not fully known. We set out to assess the effects of multiple maternal sevoflurane exposure on neurogenesis and cognitive dysfunction in fetus and offspring. Pregnant mice (gestational day 15.5) and cultured mouse neural stem cells (NSCs) received daily sevoflurane exposure (2.5% × 2 h and 4.1% × 2 h respectively) for three consecutive days. Cognitive function of the offspring was determined with the Morris water maze. The expression of Ccnd1 and Pax6 in fetal brains and NSCs were analyzed by immunofluorescence, Western blot and qPCR. The neurogenesis was evaluated by BrdU staining. Results showed that multiple sevoflurane exposure in pregnant mice caused the decrease of Pax6 and Ccnd1 expression, the inhibition of NSCs proliferation and fetal hippocampus neurogenesis, which may contribute to the impaired learning and memory in offspring at P28. Moreover, lithium mitigated the sevoflurane-induced reduction in Pax6, Ccnd1 and neurogenesis. All these results suggest that multiple sevoflurane exposure may induce detrimental effects in the developing brains of fetus and offspring by the depression of neurogenesis through Pax6 pathway. [ABSTRACT FROM AUTHOR]

Aims Increasing evidence has suggested cognitive impairment and neuronal apoptosis induced by anaesthetics are due to abnormal hyperphosphorylation of tau protein, but the detailed mechanism remains unknown. Main methods Aged mice and neurons were both exposed to 2.5% sevoflurane for 2 h. Spatial learning ability of the aged mice was tested with Morris water maze. The changes of neuroapoptosis, tau protein and cell-cycle-related factors (cyclin D1, p27) were determined using Western blot analysis. The effect of sevoflurane exposure on DNA synthesis was tested with immunofluorescent staining. Key findings We found that sevoflurane significantly impaired spatial learning ability in aged mice. In addition, total tau protein. phosphorylated tau protein, Caspase-3 and cyclin D1, but not p27Kip1 were drastically increased in the hippocampus. Consistent with the results from in vivo study, sevoflurane significantly increased the expression of cyclin D1 and Brdu positive neurons in cultured hippocampal neurons. The enhancement of cyclin D1 was partially reversed by the pharmacological inhibition of hyperphosphorylation of tau. Significance Our results suggested that cyclin D1 overexpression may result in the neuronal apoptosis through cell cycle re-entry and the deficits in postoperative cognitive dysfunction after sevoflurane exposure. Our research will improve the current understanding of the mechanisms underlying the postoperative cognitive dysfunction by anaesthetics exposure. [ABSTRACT FROM AUTHOR]

Wheat is the main food crop in the world. The planting of winter wheat in alpine regions can not only improve the land use efficiency, but also increase the income of farmers. The planting of winter wheat in alpine regions depends on whether it can survive the winter smoothly. Therefore, the study on the physiological process of winter wheat has application value.Over a three-year field experiment, the relationships between osmotic and anti-oxidative stress in tillering nodes and winter wheat overwintering capacity in alpine regions was examined. A multi-index cold-resistant overwintering capacity model of winter wheat was established using a (machine learning) logistic regression algorithm. The experiment included three winter wheat varieties (Dn1, Dn2, and J22) and eight key physiological indicators of cold resistance. The results showed that in terms of osmotic stress, the water content of tillering node was about 70%, and the Pro content was 2000-2500 μg g-1, soluble sugar content of 1000 μg g-1 above is more conducive to winter wheat overwintering; In terms of antioxidant stress ability, all indexes were maintained at a high level, which worked together to maintain the stability of antioxidant system. Through the analysis of receiver operating characteristic (ROC) curve of cold resistance of each index, six indexes of tillering node water content, hardness, pro content, soluble sugar content, MDA content and POD activity were selected to establish the cold resistance model of winter wheat overwintering, and the effect of the model was evaluated by ROC curve.The winter wheat overwintering model established in this study can provide a convenient and quick method for evaluating the overwintering capacity of novel winter wheat varieties. • Wheat wintering in alpine regions in Heilongjiang Province. • Introduced tillering node hardness index to winter wheat overwinter research. • Key physiological indicators of winter wheat overwinter examined in detail. • Osmotic stress dominates the winter wheat overwinter in alpine regions. • Established prediction model of winter wheat overwintering capacity. [ABSTRACT FROM AUTHOR]