Individualized rotation of left double lumen endobronchial tube to improve placement success rate: a randomized controlled trial.

BACKGROUND: In conventional practice, the left double lumen tube (DLT) is rotated 90° counterclockwise when the endobronchial cuff passes glottis. Success rate upon the first attempt is < 80%, likely owing to varying morphology of the bronchial bifurcation. METHODS: We conducted a randomized controlled trial to compare 90° counterclockwise rotation versus individualized degree of rotation in adult patients undergoing elective thoracic surgery using left DLT. The degree of rotation in the individualized group was based on the angle of the left main bronchi as measured on computed tomography (CT). The primary outcome was the first attempt left DLT placement success rate. RESULTS: A total of 556 patients were enrolled: 276 in the control group and 280 in the individualized group. The average angle of the left main bronchi was 100.6±9.5° (range 72° to 119°). The first attempt left DLT placement success rate was 82.6% (228/276) in the control group versus 91.4% (256/280) in the individualized group (P=0.02, χ2 test). The rate of carina mucosal injury, as measured at 30 min after the start of surgery under fibreoptic bronchoscopy, was significantly lower in individualized group than control group (14.0% versus 19.6%, P=0.041). The individualized group also had lower rate of postoperative sore throat (29.4% versus 44.0%, P<0.001) and hoarseness (16.8% versus 24.7%, P＜0.05). CONCLUSIONS: Individualized rotation of left DLT based on the angle of the left main bronchi on preoperative CT increased first attempt success rate in adult patients undergoing elective thoracic surgery. TRIAL REGISTRATION: The trial is registered at Chinese Clinical Trial Registry (ChiCTR2100053349; principal investigator Xiang Quan, date of registration November 19, 2021).

A Channel-Dimensional Feature-Reconstructed Deep Learning Model for Predicting Breast Cancer Molecular Subtypes on Overall b-Value Diffusion-Weighted MRI.

BACKGROUND: Dynamic contrast-enhanced (DCE) MRI commonly outperforms diffusion-weighted (DW) MRI in breast cancer discrimination. However, the side effects of contrast agents limit the use of DCE-MRI, particularly in patients with chronic kidney disease. PURPOSE: To develop a novel deep learning model to fully exploit the potential of overall b-value DW-MRI without the need for a contrast agent in predicting breast cancer molecular subtypes and to evaluate its performance in comparison with DCE-MRI. STUDY TYPE: Prospective. SUBJECTS: 486 female breast cancer patients (training/validation/test: 64%/16%/20%). FIELD STRENGTH/SEQUENCE: 3.0 T/DW-MRI (13 b-values) and DCE-MRI (one precontrast and five postcontrast phases). ASSESSMENT: The breast cancers were divided into four subtypes: luminal A, luminal B, HER2+, and triple negative. A channel-dimensional feature-reconstructed (CDFR) deep neural network (DNN) was proposed to predict these subtypes using pathological diagnosis as the reference standard. Additionally, a non-CDFR DNN (NCDFR-DNN) was built for comparative purposes. A mixture ensemble DNN (ME-DNN) integrating two CDFR-DNNs was constructed to identify subtypes on multiparametric MRI (MP-MRI) combing DW-MRI and DCE-MRI. STATISTICAL TESTS: Model performance was evaluated using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Model comparisons were performed using the one-way analysis of variance with least significant difference post hoc test and the DeLong test. P < 0.05 was considered significant. RESULTS: The CDFR-DNN (accuracies, 0.79 ~ 0.80; AUCs, 0.93 ~ 0.94) demonstrated significantly improved predictive performance than the NCDFR-DNN (accuracies, 0.76 ~ 0.78; AUCs, 0.92 ~ 0.93) on DW-MRI. Utilizing the CDFR-DNN, DW-MRI attained the predictive performance equal (P = 0.065 ~ 1.000) to DCE-MRI (accuracies, 0.79 ~ 0.80; AUCs, 0.93 ~ 0.95). The predictive performance of the ME-DNN on MP-MRI (accuracies, 0.85 ~ 0.87; AUCs, 0.96 ~ 0.97) was superior to those of both the CDFR-DNN and NCDFR-DNN on either DW-MRI or DCE-MRI. DATA CONCLUSION: The CDFR-DNN enabled overall b-value DW-MRI to achieve the predictive performance comparable to DCE-MRI. MP-MRI outperformed DW-MRI and DCE-MRI in subtype prediction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

High-flow nasal cannula oxygen reduced hypoxemia in patients undergoing gastroscopy under general anesthesia at ultra-high altitude: a randomized controlled trial.

BACKGROUND: Hypoxemia can occur in people at ultra-high altitude (above 3500 m) even at rest, and patients undergoing gastroscopy under general anesthesia have higher risk of hypoxemia. Supplementary oxygen via standard nasal cannula (SNC) is the standard of care for most patients who undergo gastroscopy under general anesthesia, which provides oxygen flow up to 15 L/min. High-flow nasal cannula (HFNC) could deliver oxygen at a rate up to 60 L/min, which is recommended by the American Society of Anesthesiologists Practice Guidelines. We speculated that the benefit with HFNC is more prominent in high-altitude areas, and aimed to compare the incidence of hypoxemia during gastroscopy under general anesthesia at ultra-high altitude with oxygen supply via either HFNC or SNC. METHODS: The trial was registered at at Chinese Clinical Trial Registry (ChiCTR2100045513; date of registration on 18/04/2021). Adult patients undergoing gastroscopy with anesthesia (estimated duration of anesthesia at ≥ 15 min) were randomized at a 1:1 ratio to receive HFNC oxygen or SNC oxygen. The primary outcome was hypoxemia (SpO2 < 90% for any duration). Secondary outcomes included severe hypoxemia (SpO2 < 75% for any duration or SpO2 < 90% but ≥ 75% for ≥ 60 s) and hypotension, as defined by reduction of mean arterial blood pressure by ≥ 25% from the baseline. RESULTS: A total of 262 patients were enrolled: 129 in the HFNC group and 133 in the SNC group. All patients received the designated intervention. Student's t-test, Mann-Whitney U test and χ2 test were employed in the study. The rate of hypoxemia was 9.3% (12/129) in the HFNC group versus 36.8% (49/133) in the SNC group [risk ratio (95% confidence interval): 0.25(0.14-0.45); P < 0.001). The HFNC group also had lower rate of severe hypoxemia [0.0% (0/129) versus 11.3% (15/133); risk ratio (95% confidence interval): 0.03(0.00-0.55); P < 0.001, respectively]. The rate of hypotension did not differ between the 2 groups [22.5% (29/129) in HFNC group versus 21.1% (28/133) in SNC group; risk ratio (95% confidence interval): 1.07(0.67-1.69) ; P = 0.779]. CONCLUSION: HFNC oxygen reduced the incidence of hypoxemia during anesthesia in adult patients undergoing gastroscopy at ultra-high altitude.

Differences between resident self-assessments and faculty- assessments on Anesthesiology Milestones and associated factors: a cross-sectional study.

BACKGROUND: Accurate self-assessment is crucial for the professional development of physicians. There has been sparse data on the accuracy of self-assessments on Anesthesiology Milestones. The aim of this study was to investigate the differences between resident self-assessments and faculty-assessments on Anesthesiology Milestones and the associated factors. METHODS: This was a cross-sectional study conducted in a general tertiary university-affiliated hospital. We included anesthesia residents who were enrolled in the standardized residency training program in postgraduate year two and three at the time of the Milestone evaluation. We requested evaluations of competencies from both the Clinical Competency Committee faculty and the anesthesia residents themselves, utilizing the Chinese version of Anesthesiology Milestones in January 2023 and January 2024. The primary outcome was the differences between self- and faculty-assessments, calculated by subtracting the faculty-rated score from the self-rated score on each subcompetency. RESULTS: A total of 46 and 42 residents were evaluated in year 2023 and 2024, respectively. The self-rated sum score was significantly higher than that rated by faculty [mean (standardized deviation): 120.39 (32.41) vs. 114.44 (23.71), P = 0.008 in paired t test] with an intraclass correlation coefficient of 0.55 [95% confidence interval (CI): 0.31 to 0.70]. The Bland-Altman plots revealed significant overestimation in patient care (bias 0.32, 95% CI: 0.05 to 0.60), practice-based learning and improvement (bias 0.45, 95% CI: 0.07 to 0.84), and professionalism (bias 0.37, 95% CI: 0.02 to 0.72). Ratings from residents with master's degrees (mean difference: -1.06, 95% CI: -1.80 to -0.32, P = 0.005) and doctorate degrees (mean difference: -1.14, 95% CI: -1.91 to -0.38, P = 0.003) were closer to the faculty-assessments than residents with bachelor's degrees. Compared with patient care, the differences between self- and faculty- rated scores were smaller in medical knowledge (mean difference: -0.18, 95% CI: -0.35 to -0.02, P = 0.031) and interpersonal and communication skills (mean difference: -0.41, 95% CI: -0.64 to -0.19, P < 0.001) in the generalized estimating equation logistic regression model. CONCLUSIONS: This study revealed that residents tended to overestimate themselves, emphasizing the need to improve the accuracy of Milestones self-assessment. The differences between self- and faculty-assessments were associated with residents' degrees and domains of competency.

[Comparison of Two Methods With a Left-Sided Double-Lumen Tube for Endobronchial Intubation].

Objective To compare the success rates of two methods for endobronchial intubation:the left-sided double-lumen tube(DLT) rotated 90° counter-clockwise with the patient head at the mid positon and the tube rotated 180° counter-clockwise with the patient head turned to the right. Methods Six hundred and forty-eight patients were enrolled in this study,who were to undergo elective thoracic surgery by left-sided DLT intubation in the Peking Union Medical College Hospital from December 2021 to June 2022.They were randomized into a 90° group and a 180° group,with 324 patients in each group.In the 90° group,with the patient head kept at the mid position,the left-sided DLT was advanced until the bronchial cuff passed the vocal cords and then rotated 90° counter-clockwise.In the 180°group,with the left mandible angle of each patient in the straight line with the sternum,the tube was advanced until the bronchial cuff passed the vocal cords and then rotated 180° counter-clockwise.The intubation success rate and the intubation-related complications such as carina mucosal injuries were compared between the two groups. Results The 648 patients included 336 males and 312 females,with the age ranging from 39.0 to 75.0 years old and the average age of(54.6±9.0) years old.The success rate of first intubation was 80.3% in the 90° group and 75.0% in the 180° group,which showed no significant difference(P=0.109).The success rate of second intubation was higher in the 180° group than in the 90° group(P<0.001).The rate of carina mucosal injuries was 23.8% in the 90° group and 25.6% in the 180° group,which showed no significant difference(P=0.585). Conclusions Compared with the conventional method(90°),the intubation of the left-sided DLT rotated 180° counter-clockwise with the patient head turned to the right cannot improve the success rate of the first intubation.However,it could improve the success rate of reintubation as a remedy.

What we have learned from a patient with partial tracheal rupture caused by penetrating neck injuries: a case report.

BACKGROUND: Airway management of patients with direct airway trauma caused by penetrating neck injuries is always challenging. When a failed airway occurs and surgery access is difficult, it is crucial to find the optimal approach to save the life. We propose the concept "Cannot intubate, Cannot oxygenate, Difficult surgery access" to describe this emergency scenario. CASE PRESENTATION: We report a case of a 24-year-old woman who presented with partial tracheal rupture and pneumothorax caused by a knife stab injury to the neck. A "double setup" strategy, simultaneous preparation for orotracheal intubation and tracheotomy, was carried out before rapid sequence induction. A tracheotomy under local anesthesia or an awake intubation was not preferred in consideration that the patient had a high risk of being uncooperative owing to existing mental disease and potential smothering sensation during operation. During rapid sequence intubation, distal part of the tube penetrates the tear and creates a false lumen outside the trachea then a failed airway subsequently occurred. Rescue tracheotomy was successfully performed by an otolaryngology surgeon, with the help of limited ventilation using sequential bag-mask and laryngeal mask airway ventilation provided by an anesthesiologist, without severe sequelae. CONCLUSIONS: The endotracheal tube have a risk of penetrating the tear outside the trachea in patient with partial tracheal rupture during orotracheal intubation, and once it occurs, proceeding directly to an emergency invasive airway access with optimizing oxygenation throughout procedure might increase the chance of success in rescuing the airway.

Distress, support and psychological resilience of psychiatric nurses as second victims after violence: A cross-sectional study.

AIM: The aim is to explore the impact of violence and psychological resilience on psychiatric nurses as second victims. BACKGROUND: Workplace violence is a public health concern, seriously influencing medical staff's physical and mental health. However, few pieces of research have concentrated on psychiatric nurses as second victims. METHOD: The socio-demographic data, violence-related data, psychological resilience scale, the Chinese version of the Second Victim Experience and Support Tool were applied to conduct a cross-sectional survey on nurses from psychiatric hospitals. The multiple linear regression model identified significant variables associated with violence-related injury and resilience. RESULTS: A total of 683 nurses completed the survey, of whom 88.3% were women. The average scores of the second victims' experience and support, support and distress were 3.45 ± 0.43, 3.71 ± 0.57 and 3.19 ± 0.67, respectively. Physical violence, psychological violence, psychological influence and nursing work environment were positively correlated with the experience and support of the second victims, and innocuous violence was a negative factor, which explains 20.6% of the variation. Moreover, physical injury, nursing work environment, resilience restructuring, physical violence, psychological violence, psychological impact and disagreement about the existence of violence explained 14.8% of the distress. The innocuous violence, psychological violence and nursing work environment explained 46.2% of the support. CONCLUSIONS: Our findings suggest that nurses who are second victims after the violence mainly suffer from severe psychological distress and receive the least support for the same. IMPLICATION FOR NURSING MANAGEMENT: The study provides clues to help nursing managers' emphasis on the distress and support of second victims and provides targeted intervention based on the relevant factors and these results. The article is a cross-sectional study of psychiatric nurses, which has been approved by the ethics committee of the hospital before the survey. All the nurses who participated in the survey have been informed and agreed.

The impact of the second victim's experience and support on the career success of psychiatric nurses: The mediating effect of psychological resilience.

AIMS: We explored the mediating role of psychological resilience in the experience and support of psychiatric nurses as the second victims and their career success. BACKGROUND: Psychiatric nurses, as the primary victims of workplace violence, experience physical and psychological distress, which leads to high resignation rate and job burnout. However, not much is known about the mediating role of psychological resilience between the second victims of workplace violence and their career success. METHODS: A cross-sectional study was conducted among 683 psychiatric nurses. The participants were scored according to the Chinese career success scale, Chinese version of the psychological resilience scale for nurses and Chinese version of the second victim experience and support tool. The t-test and one-way analysis of variance were used to compare the factors affecting career success. RESULTS: Career success scores differed among nurses of different ages having different employment forms, role and working years (p < .05). Mediating effect analysis revealed that psychological resilience played a full mediating role in the experience and support of second victims and their career success. CONCLUSION: Psychological resilience-based interventions should be developed to improve the psychological adjustment ability of psychiatric nurses and to strengthen their career success. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers should create more opportunities and a harmonious working environment and enhance the management system for dealing with workplace violence.

Indole Alkaloids from a Soil-Derived Clonostachys rosea.

Clonorosins A (1) and B (2), two novel indole alkaloids featuring unprecedented 6/5/6/6/5 and 6/5/5 cores, together with seven known indole-linked 2,5-diketopiperazine alkaloids (3-9), were isolated from the soil-derived fungus Clonostachys rosea YRS-06. The new structures were proposed through HR-MS, NMR, and ECD spectroscopic data. They were established by comparing the calculated NMR, ECD, and specific rotation data with the experimental. To assist in determining the absolute configuration of the chiral carbon in the side chain of 2,5-diketopiperazine derivatives, flexible analogues 3i-3iv were synthesized and analyzed. 1 was active against Fusarium oxysporum with an MIC value of 50 µg/mL. 7 and 8 showed excellent activity against human HeLa and HepG2 cells with IC50 values of 0.12-0.60 µM.

Association Between Ascites and Clinical Findings in Patients with Acute Pancreatitis: A Retrospective Study.

BACKGROUND Complications are the most important outcome determinants for acute pancreatitis (AP). We designed this single-center retrospective study to evaluate the clinical findings (complications, disease severity, and outcomes) of 218 patients with AP and to identify variables associated with ascites. MATERIAL AND METHODS We extracted clinical data from consecutive patients with AP and divided them into 2 groups based on presence or absence of ascites. We compared disease severity, complications, and outcomes between groups. RESULTS We analyzed data from 218 patients with AP (43 with ascites and 175 without it). The patients with ascites had a more severe disease (higher incidence of pancreatic inflammation [90.70% vs 68.57%; P=0.003], higher modified computed tomography severity index score [2.00 (0.00-2.00) vs 4.00 (4.00-6.00); P<0.001], higher incidence of moderate/severe AP [53.49% vs 13.14%; P<0.001]) and poorer outcomes (higher incidence of ventilation [6.98% vs 0.57%; P=0.025] and vasopressor use [4.65% vs 0%; P=0.038], and longer hospital stays [10.00 (7.00-13.00) vs 8.00 (5.00-10.00); P=0.007]) than those without ascites. Moreover, patients with ascites also displayed a higher risk for pancreatic fluid collection (odds ratio [OR]=9.206; 95% confidence interval [CI], 2.613-32.447; P<0.001), renal failure (OR=5.732; 95% CI, 1.025-32.041; P=0.024), respiratory failure (OR=6.242; 95% CI, 1.034-37.654; P=0.029), and pleural effusion (OR=5.186; 95% CI, 1.381-19.483; P<0.001) than those without ascites. CONCLUSIONS The findings from the experience of a single center of patients with AP showed that pancreatic fluid collections, renal failure, respiratory failure, and pleural effusion were associated with the development of ascites.

Pleural Effusion Is Associated with Severe Renal Dysfunction in Patients with Acute Pancreatitis.

BACKGROUND Renal dysfunction is a leading cause of death in patients with acute pancreatitis (AP) and often occurs later than respiratory complications. Whether respiratory complications can predict renal impairment remains unclear. The aim of this study was to investigate the association between pleural effusion and renal dysfunction in AP. MATERIAL AND METHODS Medical records were reviewed from individuals who were hospitalized with AP from January 1, 2015 to December 31, 2019. The patients were divided into 2 groups, based on the presence or absence of pleural effusion on admission. Disease severity, renal function parameters, and outcomes were compared between the 2 groups. RESULTS A total of 222 patients were enrolled, 25 of whom had pleural effusion on admission and 197 who did not. Patients with AP who had pleural effusion had more serious illness (higher incidences of pancreatic inflammation, pancreatic fluid collection, and moderate-to-severe AP; worse Bedside Index for Severity in Acute Pancreatitis score; and a higher modified computed tomography severity index [all P<0.05]) plus worse outcomes (higher incidences of ventilation and vasopressor use [both P<0.05]). Moreover, patients with pleural effusion had a higher level of blood urea nitrogen and lower estimated glomerular filtration rate (both P<0.05). After adjustment for potential confounders, pleural effusion was a risk factor for renal failure in patients with AP (odds ratio 6.32, 95% confidence interval 1.08-36.78, P=0.040). CONCLUSIONS Pleural effusion is associated with severe renal dysfunction in AP. Therefore, efforts should be made to improve early recognition and timely treatment of renal failure by closely monitoring renal function in patients with AP and pleural effusion on admission.

[Analysis and Correction of Spectral Curvature in Hadamard Transform Spectrometer with DMD].

Due to the advantages of its low cost and high utilization rate of light energy and no moving parts, Hadamard transform spectrometer with DMD has become a focus in the research of spectrometer. In order to solve the reduction of spectral resolution caused by the spectral curvature of Hadamard transform spectrometer with DMD (Digital Micro-mirror Device), the spectral aliasing in the spectrometer was investigated. Firstly, the mathematical relationship of spectral aliasing to radius of spectral curvature was deduced. Then, two procedures were proposed to solve the spectral aliasing. One is making the DMD encoded spectral band accordant with the standard spectral band as far as possible by adjusting the DMD-encoded stripe, and another is correcting remaining spectral aliasing by means of data processing. Finally, by analyzing and correcting spectral curvature in six situations of the curvature radius of 15.8 x 104, 7.8 x 104, 9.7 x 104 µm and etc, we fit out the relationship of spectral aliasing and spectrum correction effect of spectral-curvature to the curvature radius. The simulation indicates that the spectral resolution increases to the resolution of optical system. It shows that the proposed methods are universal, simple and effective in the improvement of spectral resolution.

Comparison of the Airtraq laryngoscope and the GlideScope for double-lumen tube intubation in patients with predicted normal airways: a prospective randomized trial.

BACKGROUND: The Airtraq laryngoscope and the GlideScope are commonly used in many airway scenarios. However, their features have not been fully described for double-lumen tube intubation. A prospective randomized study was designed to compare their intubation performances in thoracic surgery patients. METHODS: Seventy ASA physical status I and II patients with predicted normal airway were scheduled for thoracic surgeries with double-lumen tube intubation. They were randomly assigned to one of two groups and intubated with either the Airtraq laryngoscope (group A, n = 35) or the GlideScope (group G, n = 35). Airway assessments were performed prior to anesthesia, and all patients were induced with a standard anesthetic regimen. The Cormack-Lehane grades were initially evaluated with a Macintosh laryngoscope and subsequently with the group-specific laryngoscope before intubation. Intubation time was recorded as the primary outcome. The Cormack-Lehane grade, the success of the first intubation attempt, the intubation difficulty scales and ease of tube advancement were noted. Hemodynamic variables during intubation and incidence of post-operative sore throat were documented as well. RESULTS: The intubation time of group A was shorter than that of group G (36.6 ± 20.2 s vs. 54.6 ± 25.7 s, p = 0.002). The Cormack-Lehane grade (I/II/III/IV) was significantly better in group A (33/2/0/0 vs. 28/7/0/0, p = 0.042). The mean arterial pressure and heart rate rose to higher levels during intubation with the GlideScope than with the Airtraq laryngoscope. The success of the first intubation attempt and the intubation difficulty scales were comparable between the two groups. The numbers of patients who experienced postoperative sore throat were similar (6 vs. 8) in the two groups. CONCLUSIONS: Compared with the GlideScope, the specially designed Airtraq laryngoscope might be more suitable for double-lumen tube intubations in patients with predicted normal airway. TRIAL REGISTRATION: www.chictr.org Identifier: ChiCTR-TRC-11001628.

Propofol Affects Different Human Brain Regions Depending on Depth of Sedation(△).

OBJECTIVE: To investigate the effect of propofol on brain regions at different sedation levels and the association between changes in brain region activity and loss of consciousness using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and bispectral index (BIS) monitoring. METHODS: Forty-eight participants were enrolled at Peking Union Medical College Hospital from October 2011 to March 2012 and randomly assigned to a mild or a deep sedation group using computer- generated random numbers. Preliminary tests were performed a week prior to scanning to determine target effect site concentrations based on BIS and concomitant Observer's Assessment of Alertness/Sedation scores while under propofol. Within one week of the preliminary tests where propofol dose-response was established, BOLD-fMRI was conducted to examine brain activation with the subject awake, and with propofol infusion at the sedation level. RESULTS: Mild propofol sedation inhibited left inferior parietal lobe activation. Deep sedation inhibited activation of the left insula, left superior temporal gyrus, and right middle temporal gyrus. Compared with mild sedation, deep propofol sedation inhibited activation of the left thalamus, precentral gyrus, anterior cingulate, and right basal nuclei. CONCLUSION: Mild and deep propofol sedation are associated with inhibition of different brain regions, possibly explaining differences in the respective loss of consciousness processes.

[Efficacy of entropy index in monitoring nociceptive stimulus in patients undergoing propofol-remifentanil general anesthesia].

OBJECTIVE: To evaluate the efficacy of reflex entropy (RE)/state entropy (SE) in monitoring the response to nociceptive stimulus during propofol-remifentanil infusion. METHODS: After the approval of the hospital ethics committee, sixty American Society of Anesthesiologists (ASA) classification 1-2 patients, aged 18-65 years, receiving the hypogastrium operation undergoing general anesthesia, were randomly allocated to groups A and B with different remifentanil concentrations. After the concentration of propofol and remifentanil reached balance, tetanic stimulation, intubation, and incision were performed respectively with certain intervals. RE and SE were monitored during this procedure. RESULTS: Twelve patients were withdrawn from this study due to the use of vasoactive drugs. Finally, there were 28 cases in group A and 20 cases in group B. The RE and SE were not significantly changed before and after the tetanic stimulation in both groups (all P>0.05). Both RE and SE were significantly increased after intubation in group B (both P<0.05) and after skin incision in both groups (all P<0.05). Under the same stimulation, RE and SE showed no significant difference among groups administered with different levels of remifentanil (P>0.05). CONCLUSION: Under the anesthesia with propofol+remifentanil, nociceptive response may cause the increase of RE and SE. Therefore, RE and SE may be useful parameters for monitoring the nociceptive response during general anaesthesia.

Targeted isolation, identification, and antioxidant evaluation of aromatic polyketides from a plant-derived fungus Ophiobolus cirsii LZU-1509.

There are >350 species of the Ophiobolus genus, which is not yet very well-known and lacks research reports on secondary metabolites. Three new 3,4-benzofuran polyketides 1-3, a new 3,4-benzofuran polyketide racemate 4, two new pairs of polyketide enantiomers (±)-5 and (±)-7, two new acetophenone derivatives 6 and 8, and three novel 1,4-dioxane aromatic polyketides 9-11, were isolated from a fungus Ophiobolus cirsii LZU-1509 derived from an important medicinal and economic crop Anaphalis lactea. The isolation was guided by LC-MS/MS-based GNPS molecular networking analysis. The planar structures and relative configurations were mainly elucidated by NMR and HR-ESI-MS data. Their absolute configurations were determined by using X-ray diffraction analysis and via comparing computational and experimental ECD, NMR, and specific optical rotation data. 9 possesses an unreported 5/6/6/6/5 five-ring framework with a 1,4-dioxane, and 10 and 11 feature unprecedented 6/6/6/5 and 6/6/5/6 four-ring frames containing a 1,4-dioxane. The biosynthetic pathways of 9-11 were proposed. 1-11 were nontoxic in HT-1080 and HepG2 tumor cells at a concentration of 20 µM, whereas 3 and 5 exerted higher antioxidant properties in the hydrogen peroxide-stimulated model in the neuron-like PC12 cells. They could be potential antioxidant agents for neuroprotection.

Ethanol extract of Verbena officinalis alleviates MCAO-induced ischaemic stroke by inhibiting IL17A pathway-regulated neuroinflammation.

BACKGROUND: The prevention and treatment of ischaemic stroke is a worldwide challenge, and effective clinical treatment strategies are lacking. Studies have demonstrated the efficacy of Verbena officinalis in managing cerebrovascular disorders. However, the neuroprotective bioactive components and mechanisms remain unclear. PURPOSE: To investigate the pharmacological combinatorial components and mechanism underlying the anti-ischemic stroke effect of the ethanol extract of Verbena officinalis (VO Ex). STUDY DESIGN AND METHODS: The components of VO Ex were identified by HPLC. A middle cerebral artery occlusion (MCAO) induced brain injury model was used to assess the therapeutic effect of VO Ex. The activity of the chemical components of VO Ex was evaluated using a primary astrocyte injury model induced by oxygen-glucose deprivation/reperfusion (OGD/R). RNA sequencing was used to reveal the potential targets of VO Ex against cerebral ischemia-reperfusion injury (CIRI), and the results were verified by qRT-PCR and western blotting. The key components and target binding ability were predicted by molecular docking. Finally, the mechanism of combinatorial components was verified by experiments. RESULTS: The HPLC results indicated that the main ingredients of VO Ex were hastatoside, verbenalin, acteoside, luteolin, apigenin and hispidulin. In vivo experiments showed that VO Ex improved MCAO-induced acute cerebral ischemic injury. Transcriptomic data and biological experiments suggested that VO Ex exerted therapeutic effects through IL17A signalling pathways. The in vitro experiments indicated that verbenalin, acteoside, luteolin, apigenin and hispidulin exhibited neuroprotective activities. The novel formula of VALAH, derived from the aforementioned active ingredients, exhibited superior efficacy compared to each individual component. Molecular docking and mechanistic studies have confirmed that VALAH functions in the treatment of ischaemic stroke by suppressing the activation of the IL17A signalling pathway. CONCLUSION: This work is the first to reveal that VO Ex effectively inhibits the IL17A signaling pathway and mitigates neuroinflammation following ischemic stroke. Moreover, we identified the novel formula VALAH as the bioactive combinatorial components for VO Ex. Further research suggests that the activity of VALAH is associated with IL17A-mediated regulation of neuroinflammation. This finding provides new insights into the efficacious components and mechanisms of traditional Chinese medicine.

Carbapenems versus ß-lactam and ß-lactamase inhibitors for treatment of nosocomial pneumonia: A systematic review and meta-analysis.

Background: Carbapenems and ß-lactam and ß-lactamase inhibitors (BLBLIs) have been used empirically in nosocomial pneumonia, but their efficacy and safety are controversial. Objective: We carried out a systematic review with meta-analysis to evaluate the efficacy and safety of carbapenems versus BLBLIs against nosocomial pneumonia. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, CNKI, Wangfang, VIP and Sinomed were searched systematically through April 29, 2023 for clinical trials comparing carbapenems with BLBLIs for treatment of nosocomial pneumonia. Random-effects models were used to evaluate the impact of treatment on the risk ratio (RR) of all-cause mortality, clinical response, microbiologic response, resistance by Pseudomonas aeruginosa, adverse effects (AEs), and serious adverse effects. The quality of the evidence was assessed with the Cochrane risk of bias tool. The review was registerted in the INPLASY (INPLASY202340113). Results: Seven randomized controlled trials containing 3306 patients met our inclusion criteria Our meta-analysis showed no significant difference in all-cause mortality (RR = 0.88, 95% confidence interval [CI] = 0.75-1.03, I2 = 0%) or clinical cure (1.02, 0.96-1.09, 30%) or clinical failure (1.19, 0.97-1.47, 0%) or microbiologic clinical cure (0.98, 0.89-1.06, 40%) or Pseudomonas aeruginosa resistance (RR 2.43, CI 0.86-6.81, 49%, P = 0.09) or adverse events (0.98, 0.93-1.02, 0%) between carbapenems groups versus BLBLIs groups, but a significant difference was found for severe adverse events (RR 0.83, CI 0.73-0.94, 0%). Conclusion: Differences in the prevalence of mortality, clinical cure, or clinical failure were not observed between carbapenems groups versus BLBLIs groups in terms of nosocomial pneumonia. The use of carbapenems was linked to a tendency towards the emergence of P. aeruginosa resistance, however, no statistically significant difference was observed.

Partial Substitution of Whey Protein Concentrate with Spray-Dried Porcine Plasma or Soy Protein Isolate in Milk Replacer Differentially Modulates Ileal Morphology, Nutrient Digestion, Immunity and Intestinal Microbiota of Neonatal Piglets.

Appropriate protein sources are vital for the growth, development and health of neonates. Twenty-four 2-day-old piglets were randomly divided into three groups and fed isoenergetic and isonitrogenous diets. The experimental diets included a milk replacer with 17.70% whey protein concentrate (WPC group), a milk replacer with 6% spray-dried porcine plasma isonitrogenously substituting WPC (SDPP group), and a milk replacer with 5.13% soy protein isolate isonitrogenously substituting WPC (SPI group). Neonatal piglets were fed milk replacer from postnatal day 2 (PND 2) to day 20 (PND 20). The growth performance, intestinal morphology, activities of digestive enzymes, plasma biochemical parameters, immunity-related genes, short-chain fatty acids (SCFA) and intestinal microbiota in the colonic chyme were determined. The results showed that SDPP-fed piglets had higher final BW (p = 0.05), ADG (p = 0.05) and F/G (p = 0.07) compared with WPC- and SPI-fed piglets, and SDPP-fed piglets had a lower diarrhea index (p < 0.01) from PND 2 to PND 8. SDPP-fed piglets had an increased ileal villus height (p = 0.04) and ratio of villus height to crypt depth (VCR) (p = 0.02), and increased activities of sucrase (p < 0.01), lactase (p = 0.02) and trypsin (p = 0.08) in the jejunum, compared with WPC- and SPI-fed piglets. Furthermore, SPI-fed piglets had an increased mRNA expression of IL-6 (p < 0.01) and concentration of plasma urea (p = 0.08). The results from LEfSe analysis showed that SDPP-fed piglets had a higher abundance of beneficial Butyricicoccus compared with WPC- and SPI-fed piglets, in which higher abundances of pathogenic bacteria such as Marinifilaceae, Fusobacterium and Enterococcus were observed. Moreover, SDPP-fed piglets had an increased concentration of butyric acid (p = 0.08) in the colonic chyme compared with WPC- and SPI-fed piglets. These results suggest that neonatal piglets fed milk replacer with SDPP partially substituting WPC had improved growth performance and intestinal morphology and function, associated with higher digestive enzyme activity and fewer pathogenic bacteria.