Biofluid GPNMB/osteoactivin as a potential biomarker of ageing: A cross-sectional study.

Background: Glycoprotein non-metastatic melanoma B (GPNMB)/osteoactivin was first identified in the human melanoma cell lines. GPNMB plays a key role in the anti-inflammatory and antioxidative functions as well as osteoblast differentiation, cancer progression, and tissue regeneration. Recently, GPNMB was used as an anti-aging vaccine for mice. The present study aimed to investigate the potential of biofluid GPNMB as an aging biomarker in humans using serum and urine samples from an aging Chinese population. Methods: We analyzed RNA-sequencing data (GSE132040) from 17 murine organs across different ages to assess the gene expression of potential ageing biomarkers. Spearman's correlation coefficients were used to evaluate the relationship between gene expression and age. Meanwhile, a cross-sectional population study was conducted, which included 473 participants (aged 25-91 years), a representative subset of participants from the Peng Zu Study on Healthy Ageing in China (Peng Zu Cohort). Biofluid GPNMB levels were measured by ELISA. The associations of serum and urine GPNMB levels with various clinical and anthropometrical indices were assessed using ANOVA, Kruskal-Wallis H test, and univariate and multivariate linear regression analyses. Results: In mice, the Gpnmb mRNA expression levels showed a significant positive association with age in multiple organs in mice (P < 0.05). In Peng Zu Cohort, biofluid (both serum and urine) GPNMB levels showed a positive correlation with age (P < 0.05). Univariate linear regression analysis revealed that serum GPNMB levels were negatively associated with skeletal muscle mass index (SMI, P < 0.05) and insulin-like growth factor 1 (IGF-1, P < 0.05), and urine GPNMB levels showed a negative association with total bile acids (TBA, P < 0.05). Multivariate linear regression analysis further indicated that serum GPNMB levels negatively correlated with the systemic immune-inflammation index (SII, P < 0.05), and the urine GPNMB levels maintained a negative association with TBA (P < 0.05), additionally, urine GPNMB levels in men were significantly lower than in women (P < 0.05). Conclusions: The biofluid GPNMB was a strong clinical biomarker candidate for estimating biological aging.

Clinical Effects of Ultrasound-Guided Acupotomy in Knee Osteoarthritis Treatment.

The protocol presented here demonstrates the operation method of ultrasound-guided acupotomy for knee osteoarthritis (KOA), including patient recruitment, preoperative preparation, manual operation, and postoperative care. The purpose of this protocol is to relieve pain and improve knee function in patients with KOA. A total of 60 patients with KOA admitted between June 2022 and June 2023 were treated with ultrasound-guided acupotomy. Pathological changes and knee function scores were compared before and after the treatment. After 1 week of treatment, the synovial thickness of the suprapatellar bursae was significantly lesser than before treatment (p < 0.05), the Hospital for Special Surgery Knee Score (HSS) was significantly higher than before treatment (p < 0.05), the Visual analogue scale (VAS) was significantly lower than those of the control group (p < 0.05) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were significantly lower than those of the control group (p < 0.05). Therefore, ultrasound-guided acupotomy for the treatment of KOA can reduce synovial thickness, relieve pain, improve knee joint function, and have a remarkable curative effect.

Association between mechanical power during one-lung ventilation and pulmonary complications after thoracoscopic lung resection surgery: a prospective observational study.

BACKGROUND: The role of mechanical power on pulmonary outcomes after thoracic surgery with one-lung ventilation was unclear. We investigated the association between mechanical power and postoperative pulmonary complications in patients undergoing thoracoscopic lung resection surgery. METHODS: In this single-center, prospective observational study, 622 patients scheduled for thoracoscopic lung resection surgery were included. Volume control mode with lung protective ventilation strategies were implemented in all participants. The primary endpoint was a composite of postoperative pulmonary complications during hospital stay. Multivariable logistic regression models were used to evaluate the association between mechanical power and outcomes. RESULTS: The incidence of pulmonary complications after surgery during hospital stay was 24.6% (150 of 609 patients). The multivariable analysis showed that there was no link between mechanical power and postoperative pulmonary complications. CONCLUSIONS: In patients undergoing thoracoscopic lung resection with standardized lung-protective ventilation, no association was found between mechanical power and postoperative pulmonary complications. TRIAL REGISTRATION: Trial registration number: ChiCTR2200058528, date of registration: April 10, 2022.

Multiple evidence reveals two new species and new distributions of Calocybe species (Lyophyllaceae) from northeastern China.

The Calocybe species possess notable economic and medicinal value, demonstrating substantial potential for resource utilization. The taxonomic studies of Calocybe are lacking in quality and depth. Based on the specimens collected from northeast China, this study provides a detailed description of two newly discovered species, namely Calocybebetulicola and Calocybecystidiosa, as well as two commonly found species, Calocybedecolorata and Calocybeionides. Additionally, a previously unrecorded species, C.decolorata, has recently been discovered in Jilin Province, China. The two newly discovered species can be accurately distinguished from other species within the genus Calocybe based on their distinct morphological characteristics. The primary distinguishing features of C.betulicola include its grayish-purple pileus, grayish-brown to dark purple stipe, smaller basidiomata, absence of cellular pileipellis, and its habitat on leaf litter within birch forests. Calocybecystidiosa is distinguished by its growth on the leaf litter of coniferous forests, a flesh-pink pileus, a fibrous stipe with a white tomentose covering at the base, non-cellular pileipellis, larger basidiospores, and the presence of cheilocystidia. The reconstruction of phylogenetic trees using combined ITS, nLSU, and tef1-α sequences, employing maximum likelihood and Bayesian inference analyses, showed that C.betulicola formed a cluster with C.decurrens, while C.cystidiosa clustered with C.vinacea. However, these two clusters formed separate branches themselves, which also supported the results obtained from our morphological studies. A key to the Calocybe species reported from northeast China is provided to facilitate future studies of the genus.

Effect of Volatile Anesthesia Versus Intravenous Anesthesia on Postoperative Pulmonary Complications in Patients Undergoing Minimally Invasive Esophagectomy: A Randomized Clinical Trial.

BACKGROUND: The effect of intraoperative anesthetic regimen on pulmonary outcome after minimally invasive esophagectomy for esophageal cancer is yet undetermined. The aim of this study was to determine the effect of volatile anesthesia (sevoflurane or desflurane) compared with propofol-based intravenous anesthesia on pulmonary complications after minimally invasive esophagectomy. METHODS: Patients scheduled for minimally invasive esophagectomy were randomly assigned to 1 of 3 general anesthetic regimens (sevoflurane, desflurane, or propofol). The primary outcome was the incidence of pulmonary complications within the 7 days postoperatively, which was a collapsed composite end point, including respiratory infection, pleural effusion, pneumothorax, atelectasis, respiratory failure, bronchospasm, pulmonary embolism, and aspiration pneumonitis. The severity of pulmonary complications, surgery-related complications, and other secondary outcomes were also assessed. RESULTS: Of 647 patients assessed for eligibility, 558 were randomized, and 553 were analyzed. A total of 185 patients were assigned to the sevoflurane group, 185 in the desflurane, and 183 in the propofol group. Patients receiving a volatile anesthetic (sevoflurane or desflurane) had a significantly lower incidence (36.5% vs 47.5%; odds ratio, 0.63; 95% confidence interval, 0.44-0.91; P = .013) and lower severity grade of pulmonary complications ( P = .035) compared to the patients receiving propofol. There were no statistically significant differences in other secondary outcomes between the 2 groups. CONCLUSIONS: In patients undergoing minimally invasive esophagectomy, the use of volatile anesthesia (sevoflurane or desflurane) resulted in the reduced risk and severity of pulmonary complications within the first 7 postoperative days as compared to propofol-based intravenous anesthesia.

Effect of Mechanical Ventilation Mode Type on Postoperative Pulmonary Complications After Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: It is unknown whether there is a difference in pulmonary outcome in different intraoperative ventilation modes for cardiac surgery with cardiopulmonary bypass (CPB). The aim of this trial was to determine whether patients undergoing cardiac surgery with CPB could benefit from intraoperative optimal ventilation mode. DESIGN: This was a single-center, prospective, randomized controlled trial. SETTING: The study was conducted at a single-center tertiary-care hospital. PARTICIPANTS: A total of 1,364 adults undergoing cardiac surgery with CPB participated in this trial. INTERVENTIONS: Patients were assigned randomly (1:1:1) to receive 1 of 3 ventilation modes: volume-controlled ventilation (VCV), pressure-controlled ventilation (PCV), and pressure-controlled ventilation-volume guaranteed (PCV-VG). All arms of the study received the lung-protective ventilation strategy. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of postoperative pulmonary complications (PPCs) within the first 7 postoperative days. Pulmonary complications occurred in 168 of 455 patients (36.9%) in the PCV-VG group, 171 (37.6%) in the PCV group, and 182 (40.1%) in the VCV group, respectively. There was no statistical difference in the risk of overall pulmonary complications among groups (p = 0.585). There were no significant differences in the severity grade of PPCs within 7 days, postoperative ventilation duration, intensive care unit stay, postoperative hospital stay, or 30-day postoperative mortality. CONCLUSIONS: Among patients scheduled for cardiac surgery with CPB, intraoperative ventilation mode type did not affect the risk of postoperative pulmonary complications.

The effect of driving pressure-guided versus conventional mechanical ventilation strategy on pulmonary complications following on-pump cardiac surgery: A randomized clinical trial.

STUDY OBJECTIVE: Postoperative pulmonary complications occur frequently and are associated with worse postoperative outcomes in cardiac surgical patients. The advantage of driving pressure-guided ventilation strategy in decreasing pulmonary complications remains to be definitively established. We aimed to investigate the effect of intraoperative driving pressure-guided ventilation strategy compared with conventional lung-protective ventilation on pulmonary complications following on-pump cardiac surgery. DESIGN: Prospective, two-arm, randomized controlled trial. SETTING: The West China university hospital in Sichuan, China. PATIENTS: Adult patients who were scheduled for elective on-pump cardiac surgery were enrolled in the study. INTERVENTIONS: Patients undergoing on-pump cardiac surgery were randomized to receive driving pressure-guided ventilation strategy based on positive end-expiratory pressure (PEEP) titration or conventional lung-protective ventilation strategy with fixed 5 cmH2O of PEEP. MEASUREMENTS: The primary outcome of pulmonary complications (including acute respiratory distress syndrome, atelectasis, pneumonia, pleural effusion, and pneumothorax) within the first 7 postoperative days were prospectively identified. Secondary outcomes included pulmonary complication severity, ICU length of stay, and in-hospital and 30-day mortality. MAIN RESULTS: Between August 2020 and July 2021, we enrolled 694 eligible patients who were included in the final analysis. Postoperative pulmonary complications occurred in 140 (40.3%) patients in the driving pressure group and 142 (40.9%) in the conventional group (relative risk, 0.99; 95% confidence interval, 0.82-1.18; P = 0.877). Intention-to-treat analysis showed no significant difference between study groups regarding the incidence of primary outcome. The driving pressure group had less atelectasis than the conventional group (11.5% vs 17.0%; relative risk, 0.68; 95% confidence interval, 0.47-0.98; P = 0.039). Secondary outcomes did not differ between groups. CONCLUSION: Among patients who underwent on-pump cardiac surgery, the use of driving pressure-guided ventilation strategy did not reduce the risk of postoperative pulmonary complications when compared with conventional lung-protective ventilation strategy.

Serum glycoprotein non-metastatic melanoma protein B (GPNMB) level as a potential biomarker for diabetes mellitus-related cataract: A cross-sectional study.

Background: Diabetes mellitus (DM), a metabolic disease that has attracted significant research and clinical attention over the years, can affect the eye structure and induce cataract in patients diagnosed with DM. Recent studies have indicated the relationship between glycoprotein non-metastatic melanoma protein B (GPNMB) and DM and DM-related renal dysfunction. However, the role of circulating GPNMB in DM-associated cataract is still unknown. In this study, we explored the potential of serum GPNMB as a biomarker for DM and DM-associated cataract. Methods: A total of 406 subjects were enrolled, including 60 and 346 subjects with and without DM, respectively. The presence of cataract was evaluated and serum GPNMB levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results: Serum GPNMB levels were higher in diabetic individuals and subjects with cataract than in those without DM or cataract. Subjects in the highest GPNMB tertile group were more likely to have metabolic disorder, cataract, and DM. Analysis performed in subjects with DM elucidated the correlation between serum GPNMB levels and cataract. Receiver operating characteristic (ROC) curve analysis also indicated that GPNMB could be used to diagnose DM and cataract. Multivariable logistic regression analysis illustrated that GPNMB levels were independently associated with DM and cataract. DM was also found to be an independent risk factor for cataract. Further surveys revealed the combination of serum GPNMB levels and presence of DM was associated with a more precise identification of cataract than either factor alone. Conclusions: Increased circulating GPNMB levels are associated with DM and cataract and can be used as a biomarker of DM-associated cataract.

Volatile Versus Total Intravenous Anesthesia on Postoperative Delirium in Adult Patients Undergoing Cardiac Valve Surgery: A Randomized Clinical Trial.

BACKGROUND: The effect of anesthesia regimens on postoperative delirium after on-pump cardiac valve surgery is yet undetermined. This study aimed to evaluate the effect of volatile anesthesia compared with propofol-based total intravenous anesthesia (TIVA) on the occurrence of delirium after on-pump cardiac valve surgery. METHODS: This randomized clinical trial was conducted at a university academic hospital in China, from February 2019 to January 2021. Patients scheduled for on-pump cardiac valve surgery or combined valve with coronary artery bypass grafting (CABG) surgeries were randomly assigned to receive anesthesia maintenance with either a volatile anesthetic (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was the incidence of delirium during the first 7 days after surgery, assessed using the confusion assessment method for the intensive care unit (ICU). The secondary outcomes included duration of delirium, subtypes of delirium, 30-day mortality, pain score, major morbidity (including cerebral infarction, respiratory failure, and pneumonia), duration of mechanical ventilation, and lengths of ICU and hospital stay. The statistical analysis of the primary outcome variable was by Pearson's χ 2 test. RESULTS: Among the 684 patients analyzed (mean age, 53.8 years; 381 [55.7%] women), 676 were assessed for the primary outcome. Postoperative delirium occurred in 63 of 337 (18.7%) patients receiving volatile anesthesia versus 76 of 339 (22.4%) patients receiving propofol-based TIVA (relative risk, 0.80; 95% confidence interval [CI], 0.55-1.16; P = .231). There were no significant differences between the groups in any of the secondary outcomes. CONCLUSIONS: Among patients undergoing on-pump cardiac valve surgery, anesthesia maintenance with a volatile agent did not result in significantly fewer occurrences of postoperative delirium than propofol-based TIVA.

Low LH level does not indicate poor IVF cycle outcomes with GnRh-a single trigger: a retrospective analysis.

OBJECTIVE: To compare the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle outcomes between patients with low and normal serum luteinizing hormone (LH) levels on the day after a gonadotropin-releasing hormone agonist (GnRH-a) single trigger. We further investigated the efficacy of human chorionic gonadotropin (hCG) retrigger on IVF cycle outcomes in patients with low LH levels after GnRH-a single trigger. METHODS: We retrospectively analyzed 957 infertile patients (tubal factor, ovulation disorders, male sperm factor, or unexplained infertility) who were treated with IVF/ICSI at the Chengdu Xinan Gynecology Hospital from July 2017 to December 2020. Patients received sufficient GnRH-a single trigger were divided into two groups based on the serum LH levels on the next day of trigger: normal serum LH levels (≥ 10 mIU/mL) group (control group, n = 906) and low LH levels (< 10 mIU/mL) group (experimental group, n = 51). And the efficacy of hCG retrigger on IVF/ICSI cycle outcomes in 10 patients with low LH levels after GnRH-a single trigger. RESULTS: There were no significant differences in IVF/ICSI cycle outcomes, including egg yield, two pronuclei fertilization rate, excellent embryo rate, or live birth rate of frozen-thawed embryos between patients with low and normal LH levels after GnRH-a trigger. It showed significantly higher risk of ovarian hyperstimulation syndrome in the group of low LH levels [ 0.7%(1/137) vs. 8.5%(4/47), P = 0.016] compared with the group of normal LH levels who received GnRH-a single trigger. The hCG retrigger had no obvious efficacy on cycle outcomes in patients with low LH levels, including oocytes retrieved, fertilization rate, embryo conditions, and live birth rate of frozen-thawed cycles. CONCLUSION: The IVF/ICSI cycle outcomes of patients with low LH levels on the day after GnRH-a administration were similar to those of patients with normal LH levels. Blood LH test might not be required on the day following the trigger. The hCG retrigger did not have any effect on the cycle outcomes, suggesting that immediate retriggering with hCG was unnecessary.

Effect of Volatile Anesthesia Versus Total Intravenous Anesthesia on Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial.

OBJECTIVES: The purpose of this study was to evaluate the effect of volatile anesthesia and propofol-based total intravenous anesthesia (TIVA) on postoperative pulmonary complications (PPCs) among patients undergoing cardiac surgery. DESIGN: Parallel-group, randomized controlled trial. SETTING: Single-center tertiary care hospital. PARTICIPANTS: Five hundred twenty-four patients undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: The patients were assigned randomly (1:1) to receive anesthesia maintenance with a volatile anesthetic (sevoflurane or desflurane) or propofol-based TIVA. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of postoperative pulmonary complications within the first 7 postoperative days. The PPCs occurred in 118 of 262 patients (45.0%) in the volatile anesthesia group compared with 105 of 262 patients (40.1%) in the propofol-based intravenous anesthesia group (relative risk: 1.17 [95% CI 0.96-1.42], p = 0.123). There were no significant differences in the severity of PPCs within 7 days postoperatively, the occurrence and severity grade of PPCs within 30 days, the incidence of hypoxia, and 30-day mortality. CONCLUSIONS: In adult patients undergoing cardiac surgery with cardiopulmonary bypass, general anesthesia with a volatile anesthetic compared with propofol-based TIVA had not reduced pulmonary complications within the first 7 days after surgery.

Effect of ventilation strategy during cardiopulmonary bypass on postoperative pulmonary complications after cardiac surgery: a randomized clinical trial.

BACKGROUND: To determine whether maintaining ventilation during cardiopulmonary bypass (CPB) with a different fraction of inspired oxygen (FiO2) had an impact on the occurrence of postoperative pulmonary complications (PPCs). METHODS: A total of 413 adult patients undergoing elective cardiac surgery with CPB were randomly assigned into three groups: 138 in the NoV group (received no mechanical ventilation during CPB), 138 in the LOV group (received a tidal volume (VT) of 3-4 ml/kg of ideal body weight with the respiratory rate of 10-12 bpm, and the positive end-expiratory pressure of 5-8 cmH2O during CPB; the FiO2 was 30%), and 137 in the HOV group (received the same ventilation parameters settings as the LOV group while the FiO2 was 80%). RESULTS: The primary outcomes were the incidence and severity of PPCs during hospitalization. The composite incidence of PPCs did not significantly differ between the NoV (63%), LOV (49%) and HOV (57%) groups (P = 0.069). And there was also no difference regarding the incidence of PPCs between the non-ventilation (NoV) and ventilation (the combination of LOV and HOV) groups. The LOV group was observed a lower proportion of moderate and severe pulmonary complications (grade ≥ 3) than the NoV group (23.1% vs. 44.2%, P = 0.001). CONCLUSION: Maintaining ventilation during CPB did not reduce the incidence of PPCs in patients undergoing cardiac surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800015261. Prospectively registered 19 March 2018. http://www.chictr.org.cn/showproj.aspx?proj=25982.

Differences in Immunological Landscape between EGFR-Mutated and Wild-Type Lung Adenocarcinoma.

Recent clinical trials of lung adenocarcinoma with immune checkpoint inhibitors revealed that lung adenocarcinoma patients with EGFR mutations have a poor response to immunotherapy. However, the mechanisms have not been addressed. We performed immunohistochemistry analyses of resected lung adenocarcinoma tissues with and without EGFR mutations to investigate and compare the characteristics of the tumor microenvironment (TME). We retrospectively enrolled a total of 323 lung adenocarcinoma patients (164 had EGFR mutations), and their corresponding tissue samples were analyzed by the EGFR mutation test and immunohistochemistry. We selected the markers of the immune checkpoint molecule (PD1, PD-L1, and LAG-3) and immune cell (CD3, CD4, CD8, and Foxp3) as markers of the tumor microenvironment. Our results revealed that patients had a distinct tumor microenvironment between EGFR-mutant and wild-type lung adenocarcinomas; the expression of CD3, CD4, PD-L1, and Foxp3 in EGFR-mutant tumors was significantly higher than that in wild-type tumors, while the expression of LAG3 and PD-1 showed a positive correlation with EGFR-wild-type tumors. In survival analysis, EGFR-wild-type patients had longer disease-free survival (DFS) than EGFR-mutant patients (P = 0.0065). Our research demonstrates significant differences in tumor microenvironment composition between EGFR-mutant and wild-type patients. Our findings provide novel evidence that contributes to understanding the mechanism underlying the poor efficacy of immune checkpoint inhibitors.

Isolation, structural properties, bioactivities of polysaccharides from Dendrobium officinale Kimura et. Migo: A review.

Dendrobium officinale Kimura et Migo (D. officinale) is used as herbal medicine and new food resource in China, which is nontoxic and harmless, and can be used as common food. Polysaccharide as one of the main bioactive components in D. officinale, mainly composed of glucose and mannose (Manp: Glcp = 2.01:1.00-8.82:1.00), along with galactose, xylose, arabinose, and rhamnose in different molar ratios and types of glycosidic bonds. Polysaccharides of D. officinale exhibit a variety of biological effects, including immunomodulatory, anti-tumor, gastro-protective, hypoglycemic, anti-inflammatory, hepatoprotective, and vasodilating effects. This paper presents the extraction, purification, structural characteristics, bioactivities, structure-activity relationships and analyzes gaps in the current research on D. officinale polysaccharides. In addition, based on in vitro and in vivo experiments, the possible mechanisms of bioactivities of D. officinale polysaccharides were summarized. We hope that this work may provide helpful references and promising directions for further study and development of D. officinale polysaccharides.

Comparative Effect of Propofol and Volatile Anesthetics on Postoperative Pulmonary Complications After Lung Resection Surgery: A Randomized Clinical Trial.

BACKGROUND: The effect of general anesthetics (propofol and volatile anesthetics) on pulmonary outcome after lung resection surgery with one-lung ventilation (OLV) is yet undetermined. We evaluated the effect of intravenous anesthesia (propofol) and volatile anesthesia (sevoflurane or desflurane) regimens on postoperative pulmonary complications (PPCs) in patients undergoing lung resection surgery. METHODS: This prospective, randomized controlled trial enrolled 555 adult patients scheduled for lung resection surgery with OLV. Participants were randomized to 1 of 3 general anesthetic regimens (propofol, sevoflurane, or desflurane). Standard anesthesia and ventilation protocols were followed in all groups. The primary outcome was a composite of PPCs in the first 7 postoperative days. Secondary outcomes included the severity of PPCs and major postoperative complications classification. Intergroup difference in the primary outcome was assessed for significance using the Pearson χ2 test. RESULTS: Of 837 patients who were assessed for eligibility, 555 were randomized and 545 were analyzed. One hundred and seventy-nine patients were assigned to the propofol group, 182 in the sevoflurane group, and 184 in the desflurane group. The incidence of PPCs did not differ between the combined volatile anesthetics (sevoflurane and desflurane) group and the propofol group (21.9% vs 24.0%; odds ratio, 0.89; 95% confidence interval, 0.58-1.35; P = .570). The PPCs grade and Clavien-Dindo scores did not differ significantly across groups. CONCLUSIONS: In patients undergoing lung resection surgery with OLV, general anesthesia with volatile anesthetics (sevoflurane or desflurane) did not reduce PPCs compared with propofol. No difference in secondary outcomes was observed.

Comparison of low and high inspiratory oxygen fraction added to lung-protective ventilation on postoperative pulmonary complications after abdominal surgery: A randomized controlled trial.

STUDY OBJECTIVE: Intraoperative lung-protective ventilation strategy has been recommended to reduce postoperative pulmonary complications (PPCs). However, the role of inspiratory oxygen fraction (FiO2) in this protection remains highly uncertain. We aimed to evaluate the effect of intraoperative low (30%) versus high (80%) FiO2 in the context of lung-protective ventilation strategy on PPCs in patients undergoing abdominal surgery. DESIGN: Prospective, two-arm, randomized controlled trial. SETTING: Tertiary university hospital in China. PATIENTS: A total of ASA I-III 252 patients aged ≥18, who were scheduled for elective abdominal surgery under general anesthesia were included in the study. INTERVENTION: Patients were randomly assigned to receive either 30% or 80% FiO2 during the intraoperative period. All patients received volume-controlled mechanical ventilation with lung-protective ventilation approach, which included a tidal volume of 8 ml kg-1 of predicted body weight, a positive end-expiratory pressure level of 6-8 cmH2O, and repeated recruitment maneuvers. MEASUREMENTS: The primary outcome was a composite of postoperative pulmonary complications within the first 7 postoperative days, consisting of respiratory infection, respiratory failure, bronchospasm, atelectasis, pleural effusion, pneumothorax, and aspiration pneumonitis. The severity grade of PPCs was measured as a key secondary outcome. MAIN RESULTS: Two hundred and fifty-one patients completed the trial. PPCs occurred in 43 of 125 (34.4%) patients assigned to receive 30% FiO2 compared with 59 of 126 (46.8%) patients receiving 80% FiO2 (relative risk 0.74, 97.5% confidence interval, 0.51-1.02, p = 0.045, > 0.025). The severity of PPCs within the first 7 days following surgery was attenuated significantly in the low (30%) FiO2 group (p = 0.001). CONCLUSIONS: Among patients undergoing abdominal surgery under general anesthesia, an intraoperative lung-protective ventilation strategy with 30% FiO2 compared with 80% FiO2 did not reduce the incidence of PPCs. And the use of 30% FiO2 resulted in less severe pulmonary complications.

Caspase-1 inhibition prevents neuronal death by targeting the canonical inflammasome pathway of pyroptosis in a murine model of cerebral ischemia.

AIMS: The involvement of pyroptosis in ischemic stroke remains to be established. Therefore, we used the specific pyroptosis inhibitor Vx765 as an experimental intervention target in a murine model of stroke. METHODS: A total of 564 C57BL/6 mice were subjected to photothrombotic procedures and treated via gavage with Vx765 at 1-hour post-ischemia. We subsequently assessed the expression of Gasdermin D (GSDMD), inflammasomes, caspase-1, and interleukin-1ß (IL-1ß) using immunofluorescence (IF) and Western blot (WB) analyses. We also examined ultrastructural changes of cortical neurons with transmission electron microscopy (TEM) and measured infarct volumes dynamically by magnetic resonance imaging (MRI). Moreover, we evaluated the neurologic deficits by modified neurological severity scores, the rotarod test, and Treadscan. RESULTS: Elevated expression of GSDMD and GSDMD p30, the pore-forming subunit, was evident in the peri-ischemic region on days one and three post-ischemia. The neuronal plasma, nuclear, and mitochondrial membranes showed ultrastructural damage at day three post-stroke. Elevated expression of inflammasomes, caspase-1, and IL-1ß was also present on days one and three post-injury. There were significant differences between Vx765-treated and vehicle groups in mean infarct volumes (14.36 vs 21.52 mm3 ; 12.34 vs 18.56 mm3 ; 4.13 vs 10.06 mm3 ; P < .05 at day one, three, and seven post-surgery, respectively). Mice treated with Vx765 showed better motor recovery as assessed by serial behavior tests and had better neuronal survival, which was attributable to pyroptosis inhibition, as illustrated by downregulated expression of the effector protein GSDMD, inflammasomes, caspase-1, and IL-1ß. Besides, treatment with Vx765 preserved neuronal membrane structures after the ischemic injury. CONCLUSIONS: Pyroptosis emerges as an important pathway for neuronal death in an acute ischemic stroke. Vx765, a low molecular weight drug that has proven safe in clinical epilepsy trials, has potential therapeutic value for cerebral ischemia by targeting the canonical inflammasome pathway of pyroptosis.

PROtective Ventilation with a low versus high Inspiratory Oxygen fraction (PROVIO) and its effects on postoperative pulmonary complications: protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPCs) are the most common perioperative complications following surgical site infection (SSI). They prolong the hospital stay and increase health care costs. A lung-protective ventilation strategy is considered better practice in abdominal surgery to prevent PPCs. However, the role of the inspiratory oxygen fraction (FiO2) in the strategy remains disputed. Previous trials have focused on reducing SSI by increasing the inhaled oxygen concentration but higher FiO2 (80%) was found to be associated with a greater incidence of atelectasis and mortality in recent research. The trial aims at evaluating the effect of different FiO2 added to the lung-protective ventilation strategy on the incidence of PPCs during general anesthesia for abdominal surgery. METHODS AND DESIGN: PROtective Ventilation with a low versus high Inspiratory Oxygen fraction trial (PROVIO) is a single-center, prospective, randomized controlled trial planning to recruit 252 patients undergoing abdominal surgery lasting for at least 2 h. The patients will be randomly assigned to (1) a low-FiO2 (30% FiO2) group and (2) a high-FiO2 (80% FiO2) group in the lung-protective ventilation strategy. The primary outcome of the study is the occurrence of PPCs within the postoperative 7 days. Secondary outcomes include the severity grade of PPCs, the occurrence of postoperative extrapulmonary complications and all-cause mortality within the postoperative 7 and 30 days. DISCUSSION: The PROVIO trial assesses the effect of low versus high FiO2 added to a lung-protective ventilation strategy on PPCs for abdominal surgery patients and the results should provide practical approaches to intraoperative oxygen management. TRIAL REGISTRATION: www.ChiCTR.org.cn , identifier: ChiCTR18 00014901 . Registered on 13 February 2018.

Ventilation strategies with different inhaled Oxygen conceNTration during CardioPulmonary Bypass in cardiac surgery (VONTCPB): study protocol for a randomized controlled trial.

BACKGROUND: There is no consensus on the ventilation management during cardiopulmonary bypass (CPB), and the anesthesiologists or the surgeons usually ventilate the lungs with different ventilation strategies or keep them static. Better outcomes are more likely to occur when the ventilation is administered during CPB according to the existing literatures. However, the use of high fraction of inspired oxygen (FiO2) is debatable in cardiac surgery. And the potential effects of strategies combining low tidal volume (VT) ventilation with different FiO2 during CPB on postoperative pulmonary complications (PPCs) are unclear. DESIGN: The VONTCPB trial is a single-center, prospective, double-blinded, randomized, controlled trial. We are going to recruit total 420 elective cardiac surgery patients with median sternotomy under CPB, who will be equally randomized into three different ventilation strategy groups: NoV, LOV and HOV. (1) The NoV group receives no mechanical ventilation during CPB; (2) the LOV group receives a low VT of 3-4 ml/kg of ideal body weight (IBW) with the respiratory rate (RR) of 10-12 acts/min, and the positive end-expiratory pressure (PEEP) of 5-8 cmH2O during CPB; the FiO2 is 30%; (3) the HOV group receives a low VT of 3-4 ml/kg of IBW with the RR of 10-12 acts/min, and the PEEP of 5-8 cmH2O during CPB; the FiO2 is 80%. The primary endpoints are the incidence of the composite of PPCs and the PPCs score. The secondary endpoints refer to the incidence of the oxygenation index (PaO2/FiO2 ratio) < 300 mmHg at three time points (the moment arriving in the ICU, 6 and 12 h after arrival in the ICU), the surgical incision healing grade, the intubation time, the stay of ICU, the length of hospital stay, and mortality at 30 days after the surgery. DISCUSSION: The VONTCPB trial is the first study to assess the effects of strategies combining low tidal volume (VT) ventilation with different FiO2 during CPB on patients' outcomes. TRIAL REGISTRATION: ChiCTR1800015261 . Registered on 20 March 2018.

Effect of nicotine dependence on quality of life and sleep quality in patients with lung cancer who continue to smoke after diagnosis.

BACKGROUND: Hundreds of millions of Chinese individuals continue to smoke and rates of lung cancer still continue to rise. However, there were few studies that examined the effects of nicotine dependence on quality of life (QOL) and sleep quality in lung cancer patients. This study aimed to investigate the effect of nicotine dependence on QOL and sleep quality in lung cancer patients who continue to smoke after diagnosis. METHODS: This cross-sectional survey study included 202 patients with lung cancer. Smokers were separated into two groups based on the Fagerstrom Test for Nicotine dependence: the low dependence (LD) (<4 score) group (n=59) and the high dependence (HD) (≥4 score) group (n=143). Both Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) and Chinese version of Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the two groups of lung cancer patients. Then we analyzed the difference of QOL and sleep quality between two distinct nicotine dependence groups. RESULTS: Physical functioning, role functioning, emotional functioning, cognitive functioning, global health status and social functioning items in the LD group were significantly higher than the HD group (P<0.001). Fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, diarrhea and financial problems in the LD group were significantly lower than those in the HD group (P<0.001). Significantly higher scores in the HD group were found concerning the three sleep components including sleep duration, sleep efficiency and daytime function. The mean global PSQI score in the HD group was significantly higher than the LD group (P=0.014). CONCLUSIONS: These findings suggest that lung cancer patients who continue to smoke after diagnosis should receive health education in order to improve their QOL and quality of sleep after the word education. This can be useful for clinicians and nurses who are trying to motivate smokers to quit smoking.