Association of adherence to the enhanced recovery after surgery pathway and outcomes after laparoscopic total gastrectomy.

OBJECTIVE: The current study used a composite outcome to investigate whether applying the ERAS protocol would enhance the recovery of patients undergoing laparoscopic total gastrectomy (LTG). EXPOSURES: Laparoscopic total gastrectomy and perioperative interventions were the exposure. An ERAS clinical pathway consisting of 14 items was implemented and assessed. Patients were divided into either ERAS-compliant or non-ERAS-compliant group according the adherence above 9/14 or not. MAIN OUTCOMES AND MEASURES: The primary study outcome was a composite outcome called 'optimal postoperative recovery' with the definition as below: discharge within 6 days with no sever complications and no unplanned re-operation or readmission within 30 days postoperatively. Univariate logistic regression analysis and multivariate logistic regression analysis were used to model optimal postoperative recovery and compliance, adjusting for patient-related and disease-related characteristics. RESULTS: A total of 252 patients were included in this retrospective study, 129 in the ERAS compliant group and 123 in the non-ERAS-compliant group. Of these, 79.07% of the patients in ERAS compliant group achieved optimal postoperative recovery, whereas 61.79% of patients in non-ERAS-compliant group did (P = 0.0026). The incidence of sever complications was lower in the ERAS-compliant group (1.55% vs. 6.5%, P = 0.0441). No patients in ERAS compliant group had unplanned re-operation, whereas 5.69% (7/123) of patients in non-ERAS-compliant group had (p = 0.006). The median length of the postoperative hospital stay was shorter in the in the ERAS compliant group (5.51 vs. 5.68 days, P = 0.01). Both logistic (OR 2.01, 95% CI 1.21-3.34) and stepwise regression (OR 2.07, 95% CI 1.25-3.41) analysis showed that high overall compliance with the ERAS protocol facilitated optimal recovery in such patients. In bivariate analysis of compliance for patients who had an optimal postoperative recovery, carbohydrate drinks (p = 0.0196), early oral feeding (P = 0.0043), early mobilization (P = 0.0340), and restrictive intravenous fluid administration (P < 0.0001) were significantly associated with optimal postoperative recovery. CONCLUSIONS AND RELEVANCE: Patients with higher ERAS compliance (almost 70% of the accomplishment) suffered less severe postoperative complications and were more likely to achieve optimal postoperative recovery.

Inhaled Nitric Oxide ReDuce postoperatIve pulmoNAry complicaTions in patiEnts with recent COVID-19 infection (INORDINATE): protocol for a randomised controlled trial.

BACKGROUND: A history of SARS-CoV-2 infection has been reported to be associated with an increased risk of postoperative pulmonary complications (PPCs). Even mild PPCs can elevate the rates of early postoperative mortality, intensive care unit (ICU) admission and prolong the length of ICU and/or hospital stays. Consequently, it is crucial to develop perioperative management strategies that can mitigate these increased risks in surgical patients who have recently been infected with SARS-CoV-2. Accumulating evidence suggests that nitric oxide (NO) inhalation might be effective in treating COVID-19. NO functions in COVID-19 by promoting vasodilation, anticoagulation, anti-inflammatory and antiviral effects. Therefore, our study hypothesises that the perioperative use of NO can effectively reduce PPCs in patients with recent SARS-CoV-2 infection. METHOD AND ANALYSIS: A prospective, double-blind, single-centre, randomised controlled trial is proposed. The trial aims to include participants who are planning to undergo surgery with general anaesthesia and have been recently infected with SARS-CoV-2 (within 7 weeks). Stratified allocation of eligible patients will be performed at a 1:1 ratio based on the predicted risk of PPCs using the Assess Respiratory Risk in Surgical Patients in Catalonia risk index and the time interval between infection and surgery.The primary outcome of the study will be the presence of PPCs within the first 7 days following surgery, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm and aspiration pneumonitis. The primary outcome will be reported as counts (percentage) and will be compared using a two-proportion χ2 test. The common effect across all primary components will be estimated using a multiple generalised linear model. ETHICS AND DISSEMINATION: The trial is approved by the Institutional Review Board of Xijing Hospital (KY20232058-F1). The findings, including positive, negative and inconclusive results, will be published in scientific journals with peer-review processes. TRIAL REGISTRATION NUMBER: NCT05721144.

The origin of different bending stiffness between double-stranded RNA and DNA revealed by magnetic tweezers and simulations.

The subtle differences in the chemical structures of double-stranded (ds) RNA and DNA lead to significant variations in their biological roles and medical implications, largely due to their distinct biophysical properties, such as bending stiffness. Although it is well known that A-form dsRNA is stiffer than B-form dsDNA under physiological salt conditions, the underlying cause of this difference remains unclear. In this study, we employ high-precision magnetic-tweezer experiments along with molecular dynamics simulations and reveal that the relative bending stiffness between dsRNA and dsDNA is primarily determined by the structure- and salt-concentration-dependent ion distribution around their helical structures. At near-physiological salt conditions, dsRNA shows a sparser ion distribution surrounding its phosphate groups compared to dsDNA, causing its greater stiffness. However, at very high monovalent salt concentrations, phosphate groups in both dsRNA and dsDNA become fully neutralized by excess ions, resulting in a similar intrinsic bending persistence length of approximately 39 nm. This similarity in intrinsic bending stiffness of dsRNA and dsDNA is coupled to the analogous fluctuations in their total groove widths and further coupled to the similar fluctuation of base-pair inclination, despite their distinct A-form and B-form helical structures.

Microbial interventions in yak colibacillosis: Lactobacillus-mediated regulation of intestinal barrier.

Introduction: The etiology of Escherichia coli in yaks, along with its drug resistance, results in economic losses within the yak breeding industry. The utilization of lactic acid bacteria treatment has emerged as a viable alternative to antibiotics in managing colibacillosis. Methods: To elucidate the therapeutic mechanisms of Lactobacillus against Escherichia coli-induced intestinal barrier damage in yaks, we employed yak epithelial cells as the experimental model and established a monolayer epithelial barrier using Transwell. The study encompassed four groups: a control group, a model group (exposed to E. coli O78), a low-dose Lactobacillus group (E. coli O78 + 1 × 105CFU LAB), and a high-dose Lactobacillus group (E. coli O78 + 1 × 107CFU LAB). Various techniques, including transmembrane resistance measurement, CFU counting, RT-qPCR, and Western Blot, were employed to assess indicators related to cell barrier permeability and tight junction integrity. Results: In the Model group, Escherichia coli O78 significantly compromised the permeability and tight junction integrity of the yak epithelial barrier. It resulted in decreased transmembrane resistance, elevated FD4 flux, and bacterial translocation. Furthermore, it downregulated the mRNA and protein expression of MUC2, Occludin, and ZO-1, while upregulating the mRNA expression and protein expression of FABP2 and Zonulin, thereby impairing intestinal barrier function. Contrastingly, Lactobacillus exhibited a remarkable protective effect. It substantially increased transmembrane resistance, mitigated FD4 flux, and reduced bacterial translocation. Moreover, it significantly upregulated the mRNA and protein expression of MUC2, Occludin, and ZO-1, while downregulating the mRNA and protein expression of FABP2 and Zonulin. Notably, high-dose LAB demonstrated superior regulatory effects compared to the low-dose LAB group. Discussion: In conclusion, our findings suggest that Lactobacillus holds promise in treating yak colibacillosis by enhancing mucin and tight junction protein expression. Furthermore, we propose that Lactobacillus achieves these effects through the regulation of Zonulin.

Association between postoperative nadir platelet count and postoperative cardiovascular complications following septal myectomy in patients with hypertrophic cardiomyopathy: a retrospective cohort study.

BACKGROUND: Platelet count is associated with cardiovascular risk and mortality in several cardiovascular diseases, but the association of the nadir platelet counts post-septal myectomy with the cardiovascular complication risk in hypertrophic obstructive cardiomyopathy patients remains unclear. METHODS: This retrospective cohort study reviewed all adult patients who underwent septal myectomy at a single tertiary referral center over a 5-year period. Postoperative nadir platelet count was defined as the lowest platelet count in the first 4 postoperative days or until hospital discharge. The composite outcome included cardiovascular death, myocardial infarction, heart failure, malignant arrhythmia, cardiac tamponade, and major bleeding events within 30 days postoperatively. Univariable and multivariable logistic regression and restricted cubic spline models were used to assess the association between postoperative nadir platelet count and the 30-day postoperative cardiovascular complication risk. RESULTS: Among the 113 enrolled patients, 23 (20.4%) developed cardiovascular events within 30 days postoperatively. The incidence of postoperative cardiovascular complications was significantly higher in patients with a nadir platelet count ≤ 99 × 109/L than in those with a nadir platelet count > 99 × 109/L (33.3% vs. 7.1%, crude risk ratio: 4.67, 95% confidence interval: 1.69-12.85, P < 0.001). Multivariable logistic regression revealed that postoperative nadir platelet count was negatively associated with 30-day postoperative cardiovascular complications (adjusted odds ratio: 0.97; 95% confidence interval: 0.95-0.99; P = 0.005) and the association was linear (Pnonlinearity = 0.058) after full adjustment. The association between nadir platelet count and cardiovascular complications within 30 days post-surgery was consistent in all predefined subgroups (Pinteraction > 0.05). CONCLUSION: The postoperative nadir platelet count was significantly associated with the 30-day post-myectomy risk of cardiovascular complications in hypertrophic obstructive cardiomyopathy patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT04275544).

Microglia enhance post-anesthesia neuronal activity by shielding inhibitory synapses.

Microglia are resident immune cells of the central nervous system and play key roles in brain homeostasis. During anesthesia, microglia increase their dynamic process surveillance and interact more closely with neurons. However, the functional significance of microglial process dynamics and neuronal interaction under anesthesia is largely unknown. Using in vivo two-photon imaging in mice, we show that microglia enhance neuronal activity after the cessation of isoflurane anesthesia. Hyperactive neuron somata are contacted directly by microglial processes, which specifically colocalize with GABAergic boutons. Electron-microscopy-based synaptic reconstruction after two-photon imaging reveals that, during anesthesia, microglial processes enter into the synaptic cleft to shield GABAergic inputs. Microglial ablation or loss of microglial ß2-adrenergic receptors prevents post-anesthesia neuronal hyperactivity. Our study demonstrates a previously unappreciated function of microglial process dynamics, which enable microglia to transiently boost post-anesthesia neuronal activity by physically shielding inhibitory inputs.

Metagenomic analysis for exploring the potential of Lactobacillus yoelii FYL1 to mitigate bacterial diarrhea and changes in the gut microbiota of juvenile yaks.

Diarrhea in calves is a common disease that results in poor nutrient absorption, poor growth and early death which leads to productivity and economic losses. Therefore, it is important to explore the methods to reduce diarrhea in yak's calves. Efficacy of lactic acid bacteria (LAB) for improvement of bacterial diarrhea is well recognized. For this purpose, two different doses (107 CFU, 1011 CFU) of Lactobacillus yoelii FYL1 isolated from yaks were fed to juvenile yaks exposed to E. coli O78. After a trial period of ten days fresh feces and intestinal contents of the experimental yaks were collected and metagenomics sequencing was performed. It was found that feeding a high dose of Lactobacillus yoelii FYL1 decreased abundance of phylum Firmicutes in the E. coli O78 infected group whereas, it was high in animals fed low dose of Lactobacillu yoelii FYL1. Results also revealed that counts of bacteria from the family Oscillospiraceae, genus Synergistes and Megasphaera were higher in control group whereas, order Bifidobacteriales and family Bifidobacteriaceae were higher in infected group. It was observed that bacterial counts for Pseudoruminococcus were significantly (P < 0.05) higher in animals of group that were given high dose of Lactobacillus yoelii FYL1 (HLAB). Compared to infected group multiple beneficial bacterial genera such as Deinococus and Clostridium were found higher in the animals that were given a low dose of Lactobacillus yoelii FYL1 (LLAB). The abundance of pathogenic bacterial genera that included Parascardovia, Bacteroides and Methanobrevibacter was decreased (P < 0.05) in the lower dose treated group. The results of functional analysis revealed that animals of LLAB had a higher metabolism of terpenoids and polyketides compared to animals of infected group. Virus annotation also presented a significant inhibitory effect of LLAB on some viruses (P < 0.05). It was concluded that L. yoelii FYL1 had an improved effect on gut microbiota of young yaks infected with E. coli O78. This experiment contributes to establish the positive effects of LAB supplementation while treating diarrhea.

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain.

Chronic pain often develops severe mood changes such as depression. However, how chronic pain leads to depression remains elusive and the mechanisms determining individuals' responses to depression are largely unexplored. Here we found that depression-like behaviors could only be observed in 67.9% of mice with chronic neuropathic pain, leaving 32.1% of mice with depression resilience. We determined that the spike discharges of the ventral tegmental area (VTA)-projecting lateral habenula (LHb) glutamatergic (Glu) neurons were sequentially increased in sham, resilient and susceptible mice, which consequently inhibited VTA dopaminergic (DA) neurons through a LHbGlu-VTAGABA-VTADA circuit. Furthermore, the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner. Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain. Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

Exploring the induction of endometrial epithelial cell apoptosis in clinical-type endometritis in yaks through the cyt-c/caspase-3 signaling axis.

Endometritis is a significant contributor to reduced productivity in yaks in Tibet, China. The Cyt-c/Caspase-3 signaling axis plays a crucial role in the mitochondrial pathway that triggers cell apoptosis due to endogenous factors. In this study, we examined the endometrial epithelial tissue of yaks with endometritis using pathological examination, immunohistochemical analysis, TUNEL staining, qRT-PCR, and Western blot. The results indicated significant changes in the apoptotic factors of the Cyt-c/Caspase-3 signaling axis. The expression levels of Bak1, Bax, Cyt-c, Apaf-1, Caspase-9, and Caspase-3 were significantly increased (P < 0.05), while the expression level of Bcl-2 was significantly decreased. Immunohistochemistry results revealed significant increase in Bak1, Bax, Cyt-c, Apaf-1, Caspase-9, and Caspase-3 expression in the cytoplasm compared to the healthy group, except for Bcl-2, which showed a significant decrease. Pathological section analysis demonstrated that clinical endometritis in yaks led to structural damage, bleeding, congestion, and inflammatory cell infiltration in the endometrial epithelium. Our study findings indicated that clinical endometritis in yaks can modulate apoptosis of endometrial epithelial cells via the Cyt-c/Caspase-3 signaling pathway, resulting in different levels of damage. This research is pioneering in exploring cell apoptosis induced by clinical endometritis in yaks, offering novel insights and potential strategies for the future prevention and treatment of endometritis in yaks.

Effect of remimazolam vs propofol on emergence from general anesthesia in patients undergoing cerebral endovascular procedures: A randomized controlled, non-inferiority trial.

STUDY OBJECTIVE: This study aimed to compare the time to emergence from general anesthesia with remimazolam versus propofol in patients undergoing cerebral endovascular procedures. DESIGN: A prospective, double-blind, randomized controlled, non-inferiority trial. SETTING: An academic hospital. PATIENTS: Adult patients scheduled for cerebral endovascular procedures. INTERVENTIONS: Patients were randomized at a 1:1 ratio to undergo surgery under general anesthesia with remimazolam (0.1 mg kg-1 for induction and 0.3-0.7 mg kg-1 h-1 for maintenance) or propofol (1-1.5 mg kg-1 for induction and 4-10 mg kg-1 h-1 for maintenance). MEASUREMENTS: The primary outcome was the time to emergence from anesthesia. The non-inferiority margin was -2.55 min in group difference. Major secondary outcomes included hypotension during induction, incidence of postoperative delirium and Modified Rankin Scale (mRs) at 30 days and 90 days after surgery. MAIN RESULTS: Of the 142 randomized patients, 129 completed the trial. In the modified intention-to-treat analysis, the mean time to emergence from anesthesia was 16.1 [10.4] min in the remimazolam group vs. 19.0 [11.2] min in the propofol group. The group difference was -2.9 min [95% CI -6.5, 0.7] (P = 0.003 for non-inferiority). The remimazolam group had lower rate of hypotension during induction (11.3% vs 25.4%, P = 0.03) and use of vasopressors during surgery (29.6% vs 62.0%, P < 0.001). The two groups did not differ in postoperative delirium and mRs at 30 and 90 days after surgery. CONCLUSIONS: In patients undergoing cerebral endovascular procedures, remimazolam did not increase the time from anesthesia vs propofol.

Ventral Tegmental Area Glutamatergic Neurons Facilitated Emergence From Isoflurane Anesthesia Involves Excitation of Lateral Septum γ-Aminobutyric Acid-ergic Neurons in Mice.

BACKGROUND: Ventral tegmental area (VTA) glutamatergic neurons promote wakefulness in the sleep-wake cycle; however, their roles and neural circuit mechanisms during isoflurane (ISO) anesthesia remain unclear. METHODS: Fiber photometry and in vivo electrophysiology were used to observe the changes in neuronal or terminal activity during ISO anesthesia and arousal processes. Optogenetic and anesthesia behaviors were used to investigate the effects of VTA glutamatergic neurons and their projections to the lateral septum (LS) during ISO anesthesia and arousal. Anterograde and retrograde tracings were performed to identify the connections between VTA glutamatergic neurons and the LS. RESULTS: Population activity and firing rates of VTA glutamatergic neurons decreased during ISO anesthesia (ISO: 95% confidence interval [CI], 0.83-2.06 Spikes.s-1 vs wake: 95% CI, 3.53-7.83 Spikes.s-1; P =.0001; n = 34 from 4 mice). Optogenetic activation of VTA glutamatergic neurons reduced the burst-suppression ratio in electroencephalography (laser: 95% CI, 13.09%-28.76% vs pre: 95% CI, 52.85%-71.59%; P =.0009; n = 6) and facilitated emergence (ChR2: 95% CI, 343.3-388.0 seconds vs mCherry: 95% CI, 447.6-509.8 seconds; P < .0001; n = 11/12) from ISO anesthesia. VTA glutamatergic neurons monosynaptically innervated LS γ-aminobutyric acid (GABA)-ergic neurons. The activity of VTA glutamatergic terminals in the LS decreased during ISO anesthesia, and optogenetic activation of the VTA glutamatergic terminals in the LS facilitated emergence from ISO anesthesia. Furthermore, optogenetic activation of VTA glutamatergic terminals increased the firing rates of LS γ-aminobutyric acid-ergic (GABAergic) neurons (laser: 95% CI, 0.85-4.03 Spikes.s-1 vs pre: 95% CI, 0.24-0.78 Spikes.s-1; P =.008; n = 23 from 4 mice) during ISO anesthesia. CONCLUSIONS: VTA glutamatergic neurons facilitated emergence from ISO anesthesia involving excitation of LS GABAergic neurons.

Association Between Loop Diuretics and Mortality in Patients With Cardiac Surgery-Associated Acute Kidney Injury: A Retrospective Propensity Score-Weighted Analysis.

BACKGROUND: Although loop diuretics (LDs) have been widely used in clinical practice, their effect on mortality when administered to patients experiencing cardiac surgery-associated acute kidney injury (CS-AKI) remains unknown. The study aimed to investigate the effectiveness of LD use in patients with CS-AKI. METHODS: Patients who underwent cardiac surgery with AKI were identified from the Medical Information Mart for Intensive Care III. Postoperative LD use in intensive care units (ICUs) was exposure. There were 2 primary outcome measures, the in-hospital mortality and ICU mortality; both were treated as time-to-event data and were analyzed via multivariable Cox proportional hazard models. Inverse probability weighting (IPW) was used to minimize bias. RESULTS: The study enrolled a total of 5478 patients, with a median age of 67 years, among which 2205 (40.3%) were women. The crude in-hospital and ICU mortality rates were significantly lower in the LD use group (525 of 4150 [12.7%] vs 434 of 1328 [32.7%], P < .001; 402 of 4150 [9.69%] vs 333 of 1328 [25.1%], P < .001). Adjusted hazard ratios suggested significant reductions in both in-hospital (hazard ratio [HR], 0.428; 95% confidence interval [CI], 0.374-0.489) and ICU mortality (HR, 0.278; 95% CI, 0.238-0.327). The IPW data showed a similar reduction, in-hospital mortality (HR, 0.434; 95% CI, 0.376-0.502) and ICU mortality (HR, 0.296; 95% CI, 0.251-0.349). Such association may act differently for patients with different fluid balance (P value for interaction < .001). CONCLUSIONS: LD use is associated with lower hospital and ICU mortality in CS-AKI patients in general. Patients under different conditions showed diverse responses toward such treatment indicating that personalized management is needed.

Association of intraoperative cerebral and somatic tissue oxygen saturation with postoperative acute kidney injury in adult patients undergoing multiple valve surgery.

BACKGROUND: The association between tissue oxygenation with postoperative acute kidney injury (AKI) in adult patients undergoing multiple valve surgery has not been specifically studied. METHODS: In this prospective exploratory cohort study, 99 patients were enrolled. The left forehead, the left forearm, the left upper thigh, and the left renal region tissue oxygen saturation using near-infrared spectroscopy were monitored. The association between each threshold and AKI was assessed. The relative and absolute thresholds were < 70%, < 75%, < 80%, < 85%, < 90%, < 95%, and < 100% baseline, and baseline-standard deviation (SD), -1.5 SD, -2 SD, -2.5 SD, and -3 SD. Multivariate logistic regression analysis was adopted to explore the association. RESULTS: AKI occurred in 53 (54%) patients. The absolute value-based SrrO2 thresholds associated with AKI were baseline-3 SD (odds ratio [OR], 4.629; 95% confidence interval [CI], 1.238-17.314; P = 0.023) and baseline-2.5 SD (OR, 2.842; 95% CI, 1.025-7.881; P = 0.045) after adjusting for the potential confounders, those are renal region tissue oxygen saturation of 55% and 60%, but not statistically significant after correcting for multiple testing (corrected P = 0.114 and 0.179, respectively). CONCLUSION: The SrrO2 desaturation, defined as < baseline - 2.5 SD or < baseline - 3 SD, may be associated with AKI. The thresholds need to be verified in future large-scale studies. TRIAL REGISTRATIONS: The study was registered at ClinicalTrials.gov, first trial registration: 26/10/2017, identifier: NCT03323203.

Differences in the EEG Power Spectrum and Cross-Frequency Coupling Patterns between Young and Elderly Patients during Sevoflurane Anesthesia.

Electroencephalography (EEG) is widely used for monitoring the depth of anesthesia in surgical patients. Distinguishing age-related EEG features under general anesthesia will help to optimize anesthetic depth monitoring during surgery for elderly patients. This retrospective cohort study included 41 patients aged from 18 to 79 years undergoing noncardiac surgery under general anesthesia. We compared the power spectral signatures and phase-amplitude coupling patterns of the young and elderly groups under baseline and surgical anesthetic depth. General anesthesia by sevoflurane significantly increased the spectral power of delta, theta, alpha, and beta bands and strengthened the cross-frequency coupling both in young and elderly patients. However, the variation in EEG power spectral density and the modulation of alpha amplitudes on delta phases was relatively weaker in elderly patients. In conclusion, the EEG under general anesthesia using sevoflurane exhibited similar dynamic features between young and elderly patients, and the weakened alteration of spectral power and cross-frequency coupling patterns could be utilized to precisely quantify the depth of anesthesia in elderly patients.

Changes in early postoperative outcomes and complications observed in a single center during the 2022 COVID-19 pandemic wave in China: A single-center ambispective cohort study.

BACKGROUND: Currently, the effect of the 2022 nationwide coronavirus disease 2019 (COVID-19) wave on the perioperative prognosis of surgical patients in China is unclear. Thus, we aimed to explore its influence on postoperative morbidity and mortality in surgical patients. METHODS: An ambispective cohort study was conducted at Xijing Hospital, China. We collected 10-day time-series data from December 29 until January 7 for the 2018-2022 period. The primary outcome was major postoperative complications (Clavien-Dindo class III-V). The association between COVID-19 exposure and postoperative prognosis was explored by comparing consecutive 5-year data at the population level and by comparing patients with and without COVID-19 exposure at the patient level. RESULTS: The entire cohort consisted of 3350 patients (age: 48.5 ± 19.2 years), including 1759 females (52.5%). Overall, 961 (28.7%) underwent emergency surgery, and 553 (16.5%) had COVID-19 exposure (from the 2022 cohort). At the population level, major postoperative complications occurred in 5.9% (42/707), 5.7% (53/935), 5.1% (46/901), 9.4% (11/117), and 22.0% (152/690) patients in the 2018-2022 cohorts, respectively. After adjusting for potential confounding factors, the 2022 cohort (80% patients with COVID-19 history) had a significantly higher postoperative major complication risk than did the 2018 cohort (adjusted risk difference [aRD], 14.9% (95% confidence interval [CI], 11.5-18.4%); adjusted odds ratio [aOR], 8.19 (95% CI, 5.24-12.81)). At the patient level, the incidence of major postoperative complications was significantly greater in patients with (24.6%, 136/553) than that in patients without COVID-19 history (6.0% [168/2797]; aRD, 17.8% [95% CI, 13.6-22.1%]; aOR, 7.89 [95% CI, 5.76-10.83]). Secondary outcomes of postoperative pulmonary complications were consistent with primary findings. These findings were verified through sensitivity analyses using time-series data projections and propensity score matching. CONCLUSION: Based on a single-center observation, patients with recent COVID-19 exposure were likely to have a high incidence of major postoperative complications. REGISTRATION: NCT05677815 at https://clinicaltrials.gov/ .

Effects of intra-operative administration of subanesthetic s-ketamine on emergence from sevoflurane anesthesia: a randomized double-blind placebo-controlled study.

BACKGROUND: Ketamine is administered in the perioperative period for its benefits in analgesia, anti-agitation and anti-depression when administered at a small dose. However, it is not clear whether the intra-operative administration of ketamine would affect emergence under sevoflurane anesthesia. To investigate this effect, we designed this trial. METHODS: In this randomized, double-blind, placebo-controlled study, we enrolled 44 female patients aged 18-60 who were scheduled to elective laparoscopic gynecological surgeries. All patients were randomly assigned to saline or s-ketamine group. In s-ketamine group, patients received 0.125 mg/kg s-ketamine 30 min after the start of surgery. In saline group, patients were administered the same volume of saline. Sevoflurane and remifentanil were used to maintain general anesthesia. The primary outcome was emergence time. We also assessed postoperative agitation, cognitive function, and delirium. In addition, we collected and analyzed prefrontal electroencephalogram (EEG) during and after general anesthesia. RESULTS: There were no significant differences in emergence time between s-ketamine group and saline group (10.80 ± 3.77 min vs. 10.00 ± 2.78 min, P = 0.457). Neither postoperative agitation (4 [3, 4] vs. 4 [3, 4], P = 0.835) nor cognitive function (25.84 ± 2.69 vs. 25.55 ± 2.19, P = 0.412) differed between groups. No postoperative delirium was observed in either group. Subanesthetic s-ketamine resulted in active EEG with decreased power of slow (-0.35 ± 1.13 dB vs. -1.63 ± 1.03 dB, P = 0.003), delta (-0.22 ± 1.11 dB vs. -1.32 ± 1.09 dB, P = 0.011) and alpha (-0.31 ± 0.71 dB vs. -1.71 ± 1.34 dB, P = 0.0003) waves and increased power of beta-gamma bands (-0.30 ± 0.89 dB vs. 4.20 ± 2.08 dB, P < 0.0001) during sevoflurane anesthesia, as well as an increased alpha peak frequency (-0.16 ± 0.48 Hz vs. 0.31 ± 0.73 Hz, P = 0.026). EEG patterns did not differ during the recovery period after emergence between groups. CONCLUSION: Ketamine administered during sevoflurane anesthesia had no apparent influence on emergence time in young and middle-aged female patients undergoing laparoscopic surgery. Subanesthetic s-ketamine induced an active prefrontal EEG pattern during sevoflurane anesthesia but did not raise neurological side effects after surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100046479 (date: 16/05/2021).

Universality in RNA and DNA deformations induced by salt, temperature change, stretching force, and protein binding.

Nucleic acid deformations play important roles in many biological processes. The physical understanding of nucleic acid deformation by environmental stimuli is limited due to the challenge in the precise measurement of RNA and DNA deformations and the complexity of interactions in RNA and DNA. Magnetic tweezers experiments provide an excellent opportunity to precisely measure DNA and RNA twist changes induced by environmental stimuli. In this work, we applied magnetic tweezers to measure double-stranded RNA twist changes induced by salt and temperature changes. We observed RNA unwinds when lowering salt concentration, or increasing temperature. Our molecular dynamics simulations revealed the mechanism: lowering salt concentration or increasing temperature enlarges RNA major groove width, which causes twist decrease through twist-groove coupling. Combining these results with previous results, we found some universality in RNA and DNA deformations induced by three different stimuli: salt change, temperature, and stretching force. For RNA, these stimuli first modify the major groove width, which is transduced into twist change through twist-groove coupling. For DNA, these stimuli first modify diameter, which is transduced into twist change through twist-diameter coupling. Twist-groove coupling and twist-diameter coupling appear to be utilized by protein binding to reduce DNA and RNA deformation energy cost upon protein binding.

Transcriptomic and antiviral analyses of PoIFN-Delta5 against porcine enteric viruses in porcine intestinal epithelial cells.

The interferon-delta family was first reported in domestic pigs and belongs to the type I interferon (IFN-I) family. The enteric viruses could cause diarrhea in newborn piglets with high morbidity and mortality. We researched the function of the porcine IFN-delta (PoIFN-δ) family in the porcine intestinal epithelial cells (IPEC-J2) cells infected with porcine epidemic diarrhea virus (PEDV). Our study found that all PoIFN-δs shared a typical IFN-I signature and could be divided into five branches in the phylogenic tree. Different strains of PEDV could induce typical IFN transitorily, and the virulent strain AH2012/12 had the strongest induction of porcine IFN-δ and IFN-alpha (PoIFN-α) in the early stage of infection. In addition, it was found that PoIFN-δ5/6/9/11 and PoIFN-δ1/2 were highly expressed in the intestine. PoIFN-δ5 had a better antiviral effect on PEDV compared to PoIFN-δ1 due to its higher induction of ISGs. PoIFN-δ1 and PoIFN-δ5 also activated JAK-STAT and IRS signaling. For other enteric viruses, transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and porcine rotavirus (PoRV), PoIFN-δ1 and PoIFN-δ5 both showed an excellent antiviral effect. Transcriptome analyses uncovered the differences in host responses to PoIFN-α and PoIFN-δ5 and revealed thousands of differentially expressed genes were mainly enriched in the inflammatory response, antigen processing and presentation, and other immune-related pathways. PoIFN-δ5 would be a potential antiviral drug, especially against porcine enteric viruses. These studies were the first to report the antiviral function against porcine enteric viruses and broaden the new acquaintances of this type of interferon though not novelly discovered.

Intestine microbiota and SCFAs response in naturally Cryptosporidium-infected plateau yaks.

Diarrhea is a severe bovine disease, globally prevalent in farm animals with a decrease in milk production and a low fertility rate. Cryptosporidium spp. are important zoonotic agents of bovine diarrhea. However, little is known about microbiota and short-chain fatty acids (SCFAs) changes in yaks infected with Cryptosporidium spp. Therefore, we performed 16S rRNA sequencing and detected the concentrations of SCFAs in Cryptosporidium-infected yaks. Results showed that over 80,000 raw and 70,000 filtered sequences were prevalent in yak samples. Shannon (p<0.01) and Simpson (p<0.01) were both significantly higher in Cryptosporidium-infected yaks. A total of 1072 amplicon sequence variants were shared in healthy and infected yaks. There were 11 phyla and 58 genera that differ significantly between the two yak groups. A total of 235 enzymes with a significant difference in abundance (p<0.001) were found between healthy and infected yaks. KEGG L3 analysis discovered that the abundance of 43 pathways was significantly higher, while 49 pathways were significantly lower in Cryptosporidium-infected yaks. The concentration of acetic acid (p<0.05), propionic acid (p<0.05), isobutyric acid (p<0.05), butyric acid (p<0.05), and isovaleric acid was noticeably lower in infected yaks, respectively. The findings of the study revealed that Cryptosporidium infection causes gut dysbiosis and results in a significant drop in the SCFAs concentrations in yaks with severe diarrhea, which may give new insights regarding the prevention and treatment of diarrhea in livestock.

Orexinergic innervations at GABAergic neurons of the lateral habenula mediates the anesthetic potency of sevoflurane.

AIMS: The circuitry mechanism associated with anesthesia-induced unconsciousness is still largely unknown. It has been reported that orexinergic neurons of the lateral hypothalamus (LHA) facilitate the emergence from anesthesia through their neuronal projections to the arousal-promoting brain areas. However, the lateral habenula (LHb), as one of the orexin downstream targets, is known for its anesthesia-promoting effect. Therefore, the current study aimed to explore whether and how the orexinergic projections from the LHA to the LHb have a regulatory effect on unconsciousness induced by general anesthesia. METHODS: We applied optogenetic, chemogenetic, or pharmacological approaches to regulate the orexinergicLHA-LHb pathway. Fiber photometry was used to assess neuronal activity. Loss or recovery of the righting reflex was used to evaluate the induction or emergence time of general anesthesia. The burst-suppression ratio and electroencephalography spectra were used to measure the anesthetic depth. RESULTS: We found that activation of the orexinergicLHA-LHb pathway promoted emergence and reduced anesthetic depth during sevoflurane anesthesia. Surprisingly, the arousal-promoting effect of the orexinergicLHA-LHb pathway was mediated by excitation of glutamate decarboxylase (GAD2)-expressing neurons, but not glutamatergic neurons in the LHb. CONCLUSION: The orexinergicLHA-LHb pathway facilitates emergence from sevoflurane anesthesia, and this effect was mediated by OxR2 in GAD2-expressing GABA neurons.