Overexpression of TaMPK3 enhances freezing tolerance by increasing the expression of ICE-CBF-COR related genes in the Arabidopsis thaliana.

Mitogen-activated protein kinases (MAPKs) play important roles in plant stress response. As a major member of the MAPK family, MPK3 has been reported to participate in the regulation of chilling stress. However, the regulatory function of wheat (Triticum aestivum ) mitogen-activated protein kinase TaMPK3 in freezing tolerance remains unknown. Dongnongdongmai No.1 (Dn1) is a winter wheat variety with strong freezing tolerance; therefore, it is important to explore the mechanisms underlying this tolerance. In this study, the expression of TaMPK3 in Dn1 was detected under low temperature and hormone treatment. Gene cloning, bioinformatics and subcellular localisation analyses of TaMPK3 in Dn1 were performed. Overexpressed TaMPK3 in Arabidopsis thaliana was obtained, and freezing tolerance phenotype observations, physiological indices and expression levels of ICE-C-repeat binding factor (CBF)-COR -related genes were determined. In addition, the interaction between TaMPK3 and TaICE41 proteins was detected. We found that TaMPK3 expression responds to low temperatures and hormones, and the TaMPK3 protein is localised in the cytoplasm and nucleus. Overexpression of TaMPK3 in Arabidopsis significantly improves freezing tolerance. TaMPK3 interacts with the TaICE41 protein. In conclusion, TaMPK3 is involved in regulating the ICE-CBF-COR cold resistance module through its interaction with TaICE41, thereby improving freezing tolerance in Dn1 wheat.

Goal-directed fluid therapy during post-resection phase in low central venous pressure assisted laparoscopic hepatectomy: a randomized controlled superiority trial.

PURPOSE: The purpose of this prospective single blinded randomized controlled trial was to find out whether goal-directed fluid therapy (GDFT) strategy in post-transection period in low central venous pressure (CVP) assisted laparoscopic hepatectomy (LH) has more benefit than traditional fluid strategy. METHODS: Between April 2020 and Dec 2021, patients who were scheduled for laparoscopic liver resection surgery were eligible to participate in the study. Patients were randomly divided into two groups: control group that received traditional fluid strategy in post-transection period in low CVP assisted laparoscopic hepatectomy and GDFT strategy group that received GDFT strategy in post-transection period. The primary outcome parameter is the incidence of postoperative complications. Secondary outcome parameters include perioperative clinical outcomes, postoperative clinical outcomes, length of hospital stay after surgery, postoperative lactic acid, fluids and vasoactive medications during the operation. RESULTS: A total of 159 patients in the control group and 160 patients in the GDFT were included. Two groups had no significant difference in the incidence of postoperative complications including pneumonia (P = 0.34), acute kidney injury (P = 0.72), hepatic insufficiency (P = 0.25), pleural effusion (P = 0.08) and seroperitoneum (P = 1.00), respectively. The amount of perioperative urine output is fewer in GDFT group than in the control group (P = 0.0354), while other perioperative variables and postoperative variables were comparable between two groups. CONCLUSIONS: The results show the implementation of GDFT strategy is not associated with fewer postoperative complications. GDFT strategy did not result in improved outcomes in low CVP-assisted laparoscopic hepatectomy.

Association of clonal haematopoiesis with severe postoperative complications in patients undergoing radical oesophagectomy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: ChiCTR2100044175 (Chinese Clinical Trial Registry, http://www.chictr.org.cn/showproj.aspx?proj=123193).

Prophylatic use of IV nalmefene to prevent epidural opioid-induced pruritus: A multicenter, randomized clinical trial.

STUDY OBJECTIVE: 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. DESIGN: A two-center, randomized, double blinded, controlled clinical trial. SETTING: The study was conducted from March 2022 to February 2023 at two tertiary care hospitals in China. PATIENTS: 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. INTERVENTIONS: The nalmefene group was prophylactically given 0.5 µg/kg nalmefene intravenously while the control group was given the same volume of saline. MEASUREMENTS: 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. MAIN RESULTS: 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. CONCLUSIONS: 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.

Maternal sevoflurane exposure increases the epilepsy susceptibility of adolescent offspring by interrupting interneuron development.

BACKGROUND: Exposure to general anesthesia influences neuronal functions during brain development. Recently, interneurons were found to be involved in developmental neurotoxicity by anesthetic exposure. But the underlying mechanism and long-term consequences remain elusive. METHODS: Pregnant mice received 2.5% sevoflurane for 6-h on gestational day 14.5. Pentylenetetrazole (PTZ)-induced seizure, anxiety- and depression-like behavior tests were performed in 30- and 60-day-old male offspring. Cortical interneurons were labeled using Rosa26-EYFP/-; Nkx2.1-Cre mice. Immunofluorescence and electrophysiology were performed to determine the cortical interneuron properties. Q-PCR and in situ hybridization (ISH) were performed for the potential mechanism, and the finding was further validated by in utero electroporation (IUE). RESULTS: In this study, we found that maternal sevoflurane exposure increased epilepsy susceptibility by using pentylenetetrazole (PTZ) induced-kindling models and enhanced anxiety- and depression-like behaviors in adolescent offspring. After sevoflurane exposure, the highly ordered cortical interneuron migration was disrupted in the fetal cortex. In addition, the resting membrane potentials of fast-spiking interneurons in the sevoflurane-treated group were more hyperpolarized in adolescence accompanied by an increase in inhibitory synapses. Both q-PCR and ISH indicated that CXCL12/CXCR4 signaling pathway downregulation might be a potential mechanism under sevoflurane developmental neurotoxicity which was further confirmed by IUE and behavioral tests. Although the above effects were obvious in adolescence, they did not persist into adulthood. CONCLUSIONS: Our findings demonstrate that maternal anesthesia impairs interneuron migration through the CXCL12/CXCR4 signaling pathway, and influences the interneuron properties, leading to the increased epilepsy susceptibility in adolescent offspring. Our study provides a novel perspective on the developmental neurotoxicity of the mechanistic link between maternal use of general anesthesia and increased susceptibility to epilepsy.

Development of a nomogram for the early prediction of PACU VAS in patients undergoing laparoscopic radical resection of colorectal cancer with fentanyl.

Introduction: To make early predictions of PACU VAS before surgery, we created a novel nomogram for the early prediction of PACU VAS in patients having laparoscopic radical excision of colorectal cancer with fentanyl. Methods: From July 2018 to December 2020, a total of 101 patients in Zhongshan Hospital Affiliated to Fudan University who underwent laparoscopic radical resection of colorectal cancer were enrolled in this study. For feature selection, a stepwise regression model was utilized. Multivariable logistic regression analysis was used to establish a prediction model. We incorporated age, gender, weight, height, fentanyl dosage during operation, operation time, and OPRM1 genotype, and this was presented with a nomogram. The nomogram's performance was evaluated in terms of discrimination and clinical utility. Results: The signature, which comprised of seven carefully chosen characteristics, was linked to the PACU VAS for the development dataset. Predictors contained in the individualized prediction nomogram included age, gender, weight, height, fentanyl dosage during operation, operation time, and OPRM1 genotype. With an area under the ROC curve of 0.877 (95% CI, 0.6874-1.0000), the model showed good discrimination. The nomogram still had good discrimination. Decision curve analysis demonstrated that the nomogram was clinically useful. Conclusions: The nomogram presented in this study incorporates age, gender, weight, height, fentanyl dosage during operation, operation time, and OPRM1 genotype and can be conveniently used to facilitate the individualized prediction of PACU VAS in patients undergoing laparoscopic radical resection of colorectal cancer with fentanyl.

Overexpression of TaMYB4 Confers Freezing Tolerance in Arabidopsis thaliana.

Freezing stress is one of the main factors limiting the growth and yield of wheat. In this study, we found that TaMYB4 expression was significantly upregulated in the tillering nodes of the strong cold-resistant winter wheat variety Dongnongdongmai1 (Dn1) under freezing stress. Weighted gene co-expression network analysis, qRT-PCR and protein-DNA interaction experiments demonstrated that monodehydroascorbate reductase (TaMDHAR) is a direct target of TaMYB4. The results showed that overexpression of TaMYB4 enhanced the freezing tolerance of transgenic Arabidopsis. In TaMYB4 overexpression lines (OE-TaMYB4), AtMDHAR2 expression was upregulated and ascorbate-glutathione (AsA-GSH) cycle operation was enhanced. In addition, the expression of cold stress marker genes such as AtCBF1, AtCBF2, AtCBF3, AtCOR15A, AtCOR47, AtKIN1 and AtRD29A in OE-TaMYB4 lines was significantly upregulated. Therefore, TaMYB4 may increase freezing tolerance as a transcription factor (TF) in Arabidopsis through the AsA-GSH cycle and DREB/CBF signaling pathway. This study provides a potential gene for molecular breeding against freezing stress.

Opioid-Free Versus Opioid-Based Anesthesia on Postoperative Pain After Thoracoscopic Surgery: The Use of Intravenous and Epidural Esketamine.

BACKGROUND: The effectiveness and safety of opioid-free anesthesia (OFA) regimens in distinct types of surgeries remain controversial. In this study, we investigated whether OFA could reduce the occurrence of chronic postoperative pain in patients receiving video-assisted thoracoscopic surgery (VATS). METHODS: We conducted a 2-center, randomized, controlled trial from September 2021 to January 2022. A total of 162 lung tumor patients scheduled to undergo VATS were randomly divided into an opioid-based anesthesia (OA) group and an OFA group. The OA group received general anesthesia combined with thoracic epidural block using morphine, while the OFA group received general anesthesia combined with thoracic epidural block using esketamine. Patient-controlled epidural analgesia (PCEA) was used after surgery (ropivacaine and morphine for the OA group versus ropivacaine and esketamine for the OFA group). The primary end point was chronic pain rates at 3 months after VATS, which were analyzed using a logistic regression model. The secondary end points were chronic pain rates at 6 months, acute pain rates at 24 hours and 48 hours postoperatively, postoperative side effects, and perioperative variables. RESULTS: The final analysis included 159 patients. Acute postoperative pain at 24 hours occurred in 0 of the 79 (0%) patients in the OA group and 10 of the 80 (17.5%) patients in the OFA group (odds ratio, 52.14; 95% confidence interval [CI], 6.47-420.10; P < .001). Acute postoperative pain at 48 hours occurred in 3 of the 79 (3.8%) patients in the OA group and 2 of the 80 (2.5%) patients in the OFA group (odds ratio, 2.07; 95% CI, 0.99-4.32; P = .053). In this study, none of the patients had moderate or severe pain in either group at 3 and 6 months postsurgically. Mild chronic postoperative pain at 3 months occurred in 27 of the 79 (34.2%) patients in the OA group and 14 of the 80 (17.5%) patients in the OFA group (odds ratio, 3.52; 95% CI, 1.49-8.31; P = .004). At 6 months, mild chronic pain still occurred in 23 of the 79 (29.1%) patients in the OA group and 9 of the 80 (11.3%) patients in the OFA group (odds ratio, 5.55; 95% CI, 2.01-15.33; P = .001). In addition, the OFA group included fewer patients with side effects, including nausea, vomiting, and pruritus, within 48 hours after surgery. CONCLUSIONS: Replacement of opioids by esketamine, intraoperatively as intravenous injection and epidural infusion and postoperatively as epidural infusion, reduces the incidence of mild chronic postoperative pain and side effects in patients after VATS.

Sleep fMRI with simultaneous electrophysiology at 9.4 T in male mice.

Sleep is ubiquitous and essential, but its mechanisms remain unclear. Studies in animals and humans have provided insights of sleep at vastly different spatiotemporal scales. However, challenges remain to integrate local and global information of sleep. Therefore, we developed sleep fMRI based on simultaneous electrophysiology at 9.4 T in male mice. Optimized un-anesthetized mouse fMRI setup allowed manifestation of NREM and REM sleep, and a large sleep fMRI dataset was collected and openly accessible. State dependent global patterns were revealed, and state transitions were found to be global, asymmetrical and sequential, which can be predicted up to 17.8 s using LSTM models. Importantly, sleep fMRI with hippocampal recording revealed potentiated sharp-wave ripple triggered global patterns during NREM than awake state, potentially attributable to co-occurrence of spindle events. To conclude, we established mouse sleep fMRI with simultaneous electrophysiology, and demonstrated its capability by revealing global dynamics of state transitions and neural events.

Inhibition of sphingosine-1-phosphate receptor 3 suppresses ATP-induced NLRP3 inflammasome activation in macrophages via TWIK2-mediated potassium efflux.

Background: Inhibition of sphingosine kinase 1 (SphK1), which catalyzes bioactive lipid sphingosine-1-phosphate (S1P), attenuates NLRP3 inflammasome activation. S1P exerts most of its function by binding to S1P receptors (S1PR1-5). The roles of S1P receptors in NLRP3 inflammasome activation remain unclear. Materials and methods: The mRNA expressions of S1PRs in bone marrow-derived macrophages (BMDMs) were measured by real-time quantitative polymerase chain reaction (qPCR) assays. BMDMs were primed with LPS and stimulated with NLRP3 activators, including ATP, nigericin, and imiquimod. Interleukin-1ß (IL-1ß) in the cell culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Intracellular potassium was labeled with a potassium indicator and was measured by confocal microscopy. Protein expression in whole-cell or plasma membrane fraction was measured by Western blot. Cecal ligation and puncture (CLP) was induced in C57BL/6J mice. Mortality, lung wet/dry ratio, NLRP3 activation, and bacterial loads were measured. Results: Macrophages expressed all five S1PRs in the resting state. The mRNA expression of S1PR3 was upregulated after lipopolysaccharide (LPS) stimulation. Inhibition of S1PR3 suppressed NLRP3 and pro-IL-1ß in macrophages primed with LPS. Inhibition of S1PR3 attenuated ATP-induced NLRP3 inflammasome activation, enhanced nigericin-induced NLRP3 activation, and did not affect imiquimod-induced NLRP3 inflammasome activation. In addition, inhibition of S1PR3 suppressed ATP-induced intracellular potassium efflux. Inhibition of S1PR3 did not affect the mRNA or protein expression of TWIK2 in LPS-primed BMDMs. ATP stimulation induced TWIK2 expression in the plasma membrane of LPS-primed BMDMs, and inhibition of S1PR3 impeded the membrane expression of TWIK2 induced by ATP. Compared with CLP mice treated with vehicle, CLP mice treated with the S1PR3 antagonist, TY52156, had aggravated pulmonary edema, increased bacterial loads in the lung, liver, spleen, and blood, and a higher seven-day mortality rate. Conclusions: Inhibition of S1PR3 suppresses the expression of NLRP3 and pro-IL-1ß during LPS priming, and attenuates ATP-induced NLRP3 inflammasome activation by impeding membrane trafficking of TWIK2 and potassium efflux. Although inhibition of S1PR3 decreases IL-1ß maturation in the lungs, it leads to higher bacterial loads and mortality in CLP mice.

JA-induced TaMPK6 enhanced the freeze tolerance of Arabidopsis thaliana through regulation of ICE-CBF-COR module and antioxidant enzyme system.

Mitogen-activated protein kinases (MAPKs) play important roles in the stress response of plants. However, the function of MPK proteins in freeze-resistance in wheat remains unclear. Dongnongdongmai No.1 (Dn1) is a winter wheat variety with a strong freezing resistance at extremely low temperature. In this study, we demonstrated that TaMPK6 is induced by JA signaling and is involved in the modulation of Dn1 freeze resistance. Overexpression of TaMPK6 in Arabidopsis increased the survival rate of plant at -10 â„ƒ. The scavenging ability of reactive oxygen species (ROS) and the expression of cold-responsive genes CBFs and CORs were significantly enhanced in TaMPK6-overexpressed Arabidopsis, suggesting a role of TaMPK6 in activating the ICE-CBF-COR module and antioxidant enzyme system to resist freezing stress. Furthermore, TaMPK6 is localized in the nucleus and TaMPK6 interacts with TaICE41, TaCBF14, and TaMYC2 proteins, the key components in JA signaling and the ICE-CBF-COR pathway. These results suggest that JA-induced TaMPK6 may regulate freezing-resistance in wheat by interacting with the TaICE41, TaCBF14, and TaMYC2 proteins, which in turn enhances the ICE-CBF-COR pathway. Our study revealed the molecular mechanism of TaMPK6 involvement in the cold resistance pathway in winter wheat under cold stress, which provides a basis for enriching the theory of wheat cold resistance.

Comparison of the effects of sufentanil-dominant anaesthesia/analgesia and epidural anaesthesia/analgesia on postoperative immunological alterations, stress responses and prognosis in open hepatectomy: a randomized trial.

Background: Both in vitro and in animal studies have shown immunosuppressive effects of opioids which might provoke tumour growth and metastasis, while no definite results were shown in previous clinical studies. To find out the effects between general anaesthesia combined with sufentanil target-controlled infusion (SGA) and general anaesthesia combined with epidural anaesthesia (EGA) on immunological alterations, stress responses and prognosis in patients undergoing open hepatectomy, a prospective, non-inferiority, randomized-controlled study was performed. Methods: Patients with liver neoplasms undergoing open hepatectomy were randomly assigned to either SGA (n=81) or EGA (n=81) group. The primary outcome was the ratio of interferon (IFN)-γ/interleukin (IL)-4 at 24 h after surgery (T3). The secondary outcomes included immune-related cytokines, circulating immune cells, stress-related cytokines, cortisol and blood glucose, visual analogue scale scores. Plasma was sampled at five-time points [baseline/before surgery (T0), 5 min after portal block release (T1), 1 h after surgery (T2), T3, and on a postoperative day (POD)5 (T4)]. Cancer-related outcomes, including recurrence, metastasis and survival, were followed up at 3 months and 1 year after surgery. Results: The IFN-γ/IL-4 ratios were comparable between both groups at T3 {median [interquartile range (IQR)]: 20.78 (12.73-29.18) vs. 19.52 (13.98-29.29), P=0.607}. At T3, the proportions of circulating T cells were decreased, while those of B and natural killer cells were increased. The plasma level of tumour necrosis factor (TNF)-α at T2 was significantly higher in the SGA group [median (IQR): 7.45 (6.20-9.80) vs. 5.95 (4.95-7.45) pg/mL, P<0.001]. Patient-controlled intravenous analgesia was less effective than epidural analgesia on POD0 and POD2. For hepatocellular carcinoma (HCC)-related outcomes, no significant differences were found in either short- or long-term follow-ups. Conclusions: Although the levels of TNF-α were higher in the SGA group, the tumour-related immunological alterations and follow-ups showed no difference between groups. SGA appears not to be inferior to EGA regarding tumour-related immunity and prognosis. Intravenous opioid use appears not to be inferior to epidural anaesthesia, and can be used safely in HCC patients without worsening patients' prognosis. Trial Registration: Chinese Clinical Trial Registry (No. ChiCTR2000035299).

Overexpression of TaMYC2 confers freeze tolerance by ICE-CBF-COR module in Arabidopsis thaliana.

Dongnongdongmai No.1 (Dn1) is one of the few winter wheat varieties that can successfully overwinter at temperatures as low as -25°C or even lower. To date, few researches were carried to identify the freeze tolerance genes in Dn1 and applied them to improve plant resistance to extreme low temperatures. The basic helix-loop-helix (bHLH) transcription factor MYC2 is a master regulator in JA signaling, which has been reported to involve in responses to mild cold stress (2°C and 7°C). We hypothesized that MYC2 might be part of the regulatory network responsible for the tolerance of Dn1 to extreme freezing temperatures. In this study, we showed that wheat MYC2 (TaMYC2) was induced under both extreme low temperature (-10°C and-25°C) and JA treatments. The ICE-CBF-COR transcriptional cascade, an evolutionary conserved cold resistance pathway downstream of MYC2, was also activated in extreme low temperatures. We further showed that overexpression of any of the MYC2 genes from Dn1 TaMYC2A, B, D in Arabidopsis led to enhanced freeze tolerance. The TaMYC2 overexpression lines had less electrolyte leakage and lower malondialdehyde (MDA) content, and an increase in proline content, an increases antioxidant defences, and the enhanced expression of ICE-CBF-COR module under the freezing temperature. We further verified that TaMYC2 might function through physical interaction with TaICE41 and TaJAZ7, and that TaJAZ7 physically interacts with TaICE41. These results elucidate the molecular mechanism by which TaMYC2 regulates cold tolerance and lay the foundation for future studies to improve cold tolerance in plants.

The anatomical landmarks for positioning of double lumen endotracheal tube using flexible bronchoscopy: A prospective observational study.

Background: To examine the tracheobronchial anatomy and its common variations after double-lumen tube (DLT) placement, and to determine the anatomical landmarks that can be easily identified by practitioners for DLT positioning. Method: In total, 200 patients with American Society of Anesthesiologists I-II, who were aged 20-75 years and scheduled for video-assisted thoracic surgery (VATS), were prospectively enrolled. The types of DLT position in each patient was recorded [Type I, the DLT bronchial end was in the left main bronchus (LMB), and the primary carina could be observed; Type Ⅱ, the DLT bronchial end was in the right bronchus intermedius (RBI); and Type III, an unidentified trachea or bronchus wall was observed from the DLT tracheal lumen] and the main tracheobronchial tree images were collected using Flexible bronchoscopy (FB). Result: Five patients were excluded due to excessive bronchus secretions impacting image collection. Type Ⅰ, II, and III positions of DLT were detected in 134 (68.7%) patients, 28 (14.4%) patients, and 33 (16.9%) patients, respectively. Examples of the tracheobronchial tree, common features, and variations in each lung lobe were demonstrated using FB. Furthermore, image analysis showed that each superior segment orifice of the right lower lobe (RLL) and the left lower lobe (LLL) was less variable and recognizable, determining it an important anatomical landmark for DLT positioning. Conclusion: The tracheobronchial tree and its common variations after DLT placement were described. The superior segment orifice of the RLL and LLL can be considered as an important landmark for DLT positioning.

Continuous Erector Spinae Plane Block Using Programmed Intermittent Bolus Regimen versus Intravenous Patient-Controlled Opioid Analgesia Within an Enhanced Recovery Program After Open Liver Resection in Patients with Coagulation Disorder: A Randomized, Controlled, Non-Inferiority Trial.

Purpose: Postoperative pain after open hepatectomy is significant. Preoperative coagulopathy limits the use of epidural analgesia, the gold standard for pain control in open abdominal surgery. Erector spinae plane block (ESPB) is a novel regional anesthesia technique that has been shown to provide effective analgesia in abdominal surgery. In this study, we compared the analgesic efficacy of patient-controlled continuous ESPB (CESPB) with hydromorphone patient-controlled intravenous analgesia (PCIA) after right subcostal incision hepatectomies in hepatocellular carcinoma patients with preoperative coagulopathy. Patients and Methods: In this randomized, controlled, unblinded, and noninferiority trial, 120 patients were randomized to receive either CESPB or PCIA as primary postoperative analgesia together with parecoxib (40mg Q12 h IV) for 3 days after surgery. The primary outcome was the average cough-elicited pain numeric rating scales (NRS) recorded at the seven follow-up time points of 20:00 on the day of surgery and 9:00 and 15:00 on the postoperative day 1 to day 3 (POD1 to POD3). Results: The average cough-elicited pain NRS score was 2.402 in the CESPB group and 2.676 in the PCIA group. The mean difference (95% CI) was -0.274 (-0.620 to 0.072), which demonstrated the noninferiority of CESPB to PCIA. Patients in the CESPB group had less intraoperative opioid consumption, a lower incidence of moderate-to-severe pain and PONV at POD3, and early resumption of oral intake. Conclusion: CESPB provides analgesic efficacy noninferior to opioid PCIA in the context of multimodal analgesia after right subcostal incision open hepatectomy.

Developing a prediction model for estimating adrenocorticotropic hormone changes in patients undergoing scheduled open hepatectomy.

Background: Currently, there is no gold standard for monitoring patients' intraoperative stress levels under general anesthesia, while excessive stress may affect their postoperative outcomes. This prospective cohort study developed a prediction model using patients' hemodynamic parameters to predict the change in adrenocorticotropic hormone (ACTH) concentrations, one of the stress hormones, under surgical stimuli to evaluate intraoperative stress levels. Methods: A total of 205 patients undergoing scheduled open hepatectomy were enrolled in this study to investigate the correlations between ACTH levels and hemodynamic parameters. The ACTH concentration was assessed before surgery (baseline) and 10 minutes after skin incision. Blood pressure (BP) and heart rate (HR) were obtained at baseline and again at 1-minute intervals for 10 minutes after the skin incision. A logistic regression model was built to predict intraoperative stress level based on ACTH fluctuations, using the bootstrapped sampling approach. The model was validated using the internal sample. Results: Three essential variables were used in the prediction model, including two significant variables, namely, baseline ACTH and mean arterial pressure (MAP), and one variable that was close to achieving significance, that is, HR. This model was able to detect 74.9% of patients with predefined unacceptable ACTH changes. The model had an average of area under the curve (AUC) of 0.723 [95% confidence interval (CI): 0.657-0.791]. Conclusions: The model developed herein may be a potential practical method for predicting intraoperative stress levels. This prediction model may be a preliminary step to building a real-time stress model based on routine monitoring during general anesthesia, needing further validations in an external sample.

The effect of enhanced recovery after minimally invasive esophagectomy: a randomized controlled trial.

BACKGROUND: The purpose of this randomized controlled trial was to determine if enhanced recovery after surgery (ERAS) would improve outcomes for three-stage minimally invasive esophagectomy (MIE). METHODS: Patients with esophageal cancer undergoing MIE between March 2016 and August 2018 were consecutively enrolled, and were randomly divided into 2 groups: ERAS+group that received a guideline-based ERAS protocol, and ERAS- group that received standard care. The primary endpoint was morbidity after MIE. The secondary endpoints were the length of stay (LOS) and time to ambulation after the surgery. The perioperative results including the Surgical Apgar Score (SAS) and Visualized Analgesia Score (VAS) were also collected and compared. RESULTS: A total of 60 patients in the ERAS+ group and 58 patients in the ERAS- group were included. Postoperatively, lower morbidity and pulmonary complication rate were recorded in the ERAS+ group (33.3% vs. 51.7%; p = 0.04, 16.7% vs. 32.8%; p = 0.04), while the incidence of anastomotic leakage remained comparable (11.7% vs. 15.5%; p = 0.54). There was an earlier ambulation (3 [2-3] days vs. 3 [3-4] days, p = 0.001), but comparable LOS (10 [9-11.25] days vs. 10 [9-13] days; p = 0.165) recorded in ERAS+ group. The ERAS protocol led to close scores in both SAS (7.80 ± 1.03 vs. 8.07 ± 0.89, p = 0.21) and VAS (1.74 ± 0.85 vs. 1.78 ± 1.06, p = 0.84). CONCLUSIONS: Implementation of an ERAS protocol for patients undergoing MIE resulted in earlier ambulation and lower pulmonary complications, without a change in anastomotic leakage or length of hospital stay. Further studies on minimizing leakage should be addressed in ERAS for MIE.

Transcriptome analysis of the winter wheat Dn1 in response to cold stress.

BACKGROUND: Heilongjiang Province has a long and cold winter season (the minimum temperature can reach -30 ℃), and few winter wheat varieties can safely overwinter. Dongnongdongmai1 (Dn1) is the first winter wheat variety that can safely overwinter in Heilongjiang Province. This variety fills the gap for winter wheat cultivation in the frigid region of China and greatly increases the land utilization rate. To understand the molecular mechanism of the cold response, we conducted RNA-sequencing analysis of Dn1 under cold stress. RESULTS: Approximately 120,000 genes were detected in Dn1 under cold stress. The numbers of differentially expressed genes (DEGs) in the six comparison groups (0 ℃ vs. 5 ℃, -5 ℃ vs. 5 ℃, -10 ℃ vs. 5 ℃, -15 ℃ vs. 5 ℃, -20 ℃ vs. 5 ℃ and -25 ℃ vs. 5 ℃) were 11,313, 8313, 15,636, 13,671, 14,294 and 13,979, respectively. Gene Ontology functional annotation suggested that the DEGs under cold stress mainly had "binding", "protein kinase" and "catalytic" activities and were involved in "oxidation-reduction", "protein phosphorylation" and "carbohydrate metabolic" processes. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the DEGs performed important functions in cold signal transduction and carbohydrate metabolism. In addition, major transcription factors (AP2/ERF, bZIP, NAC, WRKY, bHLH and MYB) participating in the Dn1 cold stress response were activated by low temperature. CONCLUSION: This is the first study to explore the Dn1 transcriptome under cold stress. Our study comprehensively analysed the key genes involved in cold signal transduction and carbohydrate metabolism in Dn1 under cold stress. The results obtained by transcriptome analysis could help to further explore the cold resistance mechanism of Dn1 and provide basis for breeding of cold-resistant crops.

Rapid sequence induction with a "modified timing principle" of rocuronium provides excellent intubating conditions: A randomised trial.

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.