Spatially Decoupled H2O2 Activation Pathways and Multi-Enzyme Activities in Rod-Shaped CeO2 with Implications for Facet Distribution.

CeO2, particularly in the shape of rod, has recently gained considerable attention for its ability to mimic peroxidase (POD) and haloperoxidase (HPO). However, this multi-enzyme activities unavoidably compete for H2O2 affecting its performance in relevant applications. The lack of consensus on facet distribution in rod-shaped CeO2 further complicates the establishment of structure-activity correlations, presenting challenges for progress in the field. In this study, the HPO-like activity of rod-shaped CeO2 is successfully enhanced while maintaining its POD-like activity through a facile post-calcination method. By studying the spatial distribution of these two activities and their exclusive H2O2 activation pathways on CeO2 surfaces, this study finds that the increased HPO-like activity originated from the newly exposed (111) surface at the tip of the shortened rods after calcination, while the unchanged POD-like activity is attributed to the retained (110) surface in their lateral area. These findings not only address facet distribution discrepancies commonly reported in the literature for rod-shaped CeO2 but also offer a simple approach to enhance its antibacterial performance. This work is expected to provide atomic insights into catalytic correlations and guide the design of nanozymes with improved activity and reaction specificity.

All-Natural Injectable Antibacterial Hydrogel Enabled by Chitosan and Borneol.

Hydrogels with intrinsic antimicrobial capabilities based on natural strategies have been studied as a hot topic in biomedicine. Nevertheless, it is highly challenging to thoroughly develop a bacteriostatic natural hydrogel. Borneol as a traditional Chinese medicine possesses a unique broad-spectrum antibacterial activity under a membrane-breaking mechanism. In this study, a range of fully natural antibacterial hydrogels are designed and synthesized via the Schiff base cross-linking of carboxymethyl chitosan and dialdehyde dextran grafted natural borneol. The borneol with three configurations is hydrophilically modified onto dextran to boost its antibacterial activity. Also, the synergism of hydrophilic-modified borneol groups and positively charged ammonium ions of carboxymethyl chitosan make the hydrogels totally constrict the E. coli and S. aureus growth during 24 h. Furthermore, the hydrogels exhibit good in vitro cytocompatibility through cytotoxicity, protein adhesion, and hemolytic tests. In view of the injectability, the hydrogels can be delivered to the target site through a minimally invasive route. In short, this work offers a potential tactic to develop antibacterial hydrogels for the treatment of topical wound infections.

Metasurface absorber with ultra-thin thickness designed for a terahertz focal plane array detector.

Terahertz (THz) refers to electromagnetic waves with frequency from 0.1 to 10 THz, which lies between millimeter waves and infrared light. This paper proposes an ultra-thin metasurface absorber which is perfectly suited to be the signal coupling part of terahertz focal plane array (FPA) detector. The absorptance of the proposed metasurface is higher than 80% from 4.46 to 5.76 THz (25.4%) while the thickness is merely 1.12 µm (0.018 λ). Since the metasurface absorber will be applied to terahertz FPA detector which requires planar array formation, it is divided into meta-atoms. Each meta-atom consists of the same unit cell layout, and air gaps are introduced between adjacent meta-atoms to enhance the thermal isolation, which is crucial for FPA detector to obtain desired imaging results. Due to the symmetrical layout of meta-atoms, absorptance keeps stable for different polarized waves, moreover, good absorptance could also be achieved for incidence angles range of ± 30 °. Spectral measurements show good agreement with the simulation. As a result, features of ultra-thin thickness, polarization insensitivity, and high absorptance make the proposed metasurface absorber well suited to highly efficient coupling of terahertz signals in FPA detector.

Polysaccharide-Derived Ice Recrystallization Inhibitors with a Modular Design: The Case of Dextran-Based Graft Polymers.

Ice recrystallization inhibitors inspired from antifreeze proteins (AFPs) are receiving increasing interest for cryobiology and other extreme environment applications. Here, we present a modular strategy to develop polysaccharide-derived biomimetics, and detailed studies were performed in the case of dextran. Poly(vinyl alcohol) (PVA) which has been termed as one of the most potent biomimetics of AFPs was grafted onto dextran via thiol-ene click chemistry (Dex-g-PVA). This demonstrated that Dex-g-PVA is effective in IRI and its activity increases with the degree of polymerization (DP) (sizes of ice crystals were 18.846 ± 1.759 and 9.700 ± 1.920 µm with DPs of 30 and 80, respectively) and fraction of PVA. By means of the dynamic ice shaping (DIS) assay, Dex-g-PVA is found to engage on the ice crystal surfaces, thus the ice affinity accounts for their IRI activity. In addition, Dex- g-PVA displayed enhanced IRI activity compared to that of equivalent PVA alone. We speculate that the hydrophilic nature of dextran would derive PVA in a stretch conformation that favors ice binding. The modular design can not only offer polysaccharides IRI activity but also favor the ice-binding behavior of PVA.

Preoperative Vitamin D Deficiency Is Associated With Postoperative Delirium in Critically Ill Patients.

INTRODUCTION: Postoperative delirium is common, with a reported incidence of 11% to 80% in critically ill patients. Delirium is an independent prognostic factor for poor hospital outcomes. Low vitamin D concentrations are associated with a decline in cognitive function. We therefore tested the hypothesis that low preoperative serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with postoperative delirium in critically ill patients. METHOD: We conducted a retrospective analysis of adults in a surgical intensive care unit for at least 48 hours immediately after non-cardiac and non-neurosurgical operations at Cleveland Clinic between 2013 and 2018. Delirium was assessed by trained nurses using CAM-ICU twice daily for the initial 5 postoperative days. Any positive value was considered evidence of delirium. We assessed the association between 25(OH)D concentrations within a year before surgery and the incidence of postoperative delirium using logistic regression, adjusted for potential confounders. A linear spline term with a knot at 30 ng/ml, the threshold for normal 25(OH)D concentration, was added to accommodate a nonlinear relationship between 25(OH)D concentrations and delirium. RESULTS: We included 632 patients, who had a mean (SD) 25(OH)D concentration of 25 (15) ng/ml; 55% (346/632) experienced delirium. We observed an adjusted odds ratio of 1.4 (95% CI: [1.1, 1.8], P = 0.01) for delirium per 10 ng/ml decrease in 25(OH)D concentrations when patients' 25(OH)D concentrations were less than 30 ng/ml. In patients whose 25(OH)D concentrations were at least 30 ng/ml, the adjusted odds ratio was 0.9 (95% CI: [0.7, 1.1], P = 0.36). CONCLUSION: Preoperative 25(OH)D concentrations are associated with postoperative delirium in patients whose concentrations are below the normal threshold, but not at concentrations ≥30 ng/ml. A trial will be needed to determine whether the relationship is causal, and whether vitamin D supplementation before surgery might reduce the incidence of delirium.

Do It Often, Do It Better: Association Between Pairs of Experienced Subspecialty Anesthesia Caregivers and Postoperative Outcomes. A Retrospective Observational Study.

BACKGROUND: Anesthesiologists typically care for patients having a broad range of procedures. Outcomes might be improved when care is provided by caregivers experienced in particular types of surgery. We tested the hypothesis that intraoperative care provided by pairs of anesthesia caregivers having significant experience with a particular type of surgery reduces a composite of in-hospital death and 6 serious complications, including bleeding, cardiac, gastrointestinal, infectious, respiratory, and urinary complications, compared to care provided by pairs of anesthesia caregivers with less experience. METHODS: We included patients having surgery lasting at least 30 minutes. Using cluster analysis, attending anesthesiologists, and Certified Registered Nurse Anesthetists (CRNAs) were identified as experienced or inexperienced caregivers for each type of surgery at the case level. We then compared surgeries for which anesthesia was provided by a pair of experienced caregivers versus a pair of inexperienced caregivers on our composite outcome. We estimated the average relative effect (ie, the exponentiated average log odds ratio) of receiving anesthesia from an experienced versus inexperienced caregiver pair across the 7 components of the composite outcome using a generalized estimating equation (GEE) model to adjust for between-component correlation and with inverse propensity score weighing to adjust for potential confounding from a host of variables. RESULTS: A total of 8968 patients who received anesthesia care by an experienced pair were compared with 25,361 patients who received care from an inexperienced pair, adjusting for potential confounding. The incidence of composite complications (ie, any component event) was 7.6% (677/8968) for experienced pairs and 12% (2976/25,361) for inexperienced pairs (P < .001). Care by experienced pairs of caregivers was associated with lower odds of the composite outcome with an estimated average relative effect odds ratio across the individual components of 0.61 (95% confidence interval [CI], 0.54-0.71), P < .001. Among the 7 components of the primary outcome, experienced pairs of providers had significantly lower estimated odds of bleeding, infection, and mortality. CONCLUSIONS: Anesthesia care by experienced pairs was associated with fewer bleeding complications, fewer infections, shorter hospitalization, and reduced in-hospital mortality.

Acute pain after serratus anterior plane or thoracic paravertebral blocks for video-assisted thoracoscopic surgery: A noninferiority randomised trial.

BACKGROUND: Serratus anterior plane blocks (SAPBs) and thoracic paravertebral blocks (TPVBs) can both be used for video-assisted thoracic surgery. However, it remains unknown whether the analgesic efficacy of a SAPB is comparable to that of a TPVB. OBJECTIVE: We tested the primary hypothesis that SAPBs provide noninferior analgesia compared with TPVBs for video-assisted thoracic surgery. DESIGN: A noninferiority randomised trial. SETTING: Shanghai Chest Hospital, between August 2018 and November 2018. PATIENTS: Ninety patients scheduled for video-assisted thoracic lobectomy or segmentectomy were randomised. Patients were excluded if they were unable to perform the visual analogue pain scale, or surgery was converted to thoracotomy. INTERVENTIONS: Blocks were performed after induction of general anaesthesia. The three groups were paravertebral blocks (n = 30); serratus anterior plane blocks (n = 29); and general anaesthesia alone (n = 30). PRIMARY OUTCOME MEASURES: Visual analogue pain scores (0 to 10 cm) at rest and while coughing, and Prince-Henry pain scores (0 to 4 points) were used to assess postoperative analgesia at 2, 24 and 48 h after surgery. We assessed the noninferiority of SAPBs with TPVBs on all three primary pain outcomes using a delta of 1 cm or one point as appropriate. RESULTS: The mean difference (95% confidence intervals) in visual analogue scores between the SAPBs and TPVBs was -0.04 (-0.10 to 0.03) cm at rest, -0.22 (-0.43 to -0.01) cm during coughing and -0.10 (-0.25 to 0.05) for Prince-Henry pain scores. As the upper limit of the confidence intervals were less than 1 (all P < 0.001), noninferiority was claimed for all three primary outcomes. Compared with general anaesthesia alone, the VAS scores at rest and while coughing, and the Prince-Henry pain scores for the two blocks were significantly lower during the initial 2 h after surgery. CONCLUSIONS: Serratus anterior plane blocks are quicker and easier to perform than paravertebral blocks and provide comparable analgesia in patients having video-assisted thoracic surgery. Both blocks provided analgesia that was superior to general anaesthesia alone during the initial 2 h after surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR1800017671.

Mild Acute Kidney Injury after Noncardiac Surgery Is Associated with Long-term Renal Dysfunction: A Retrospective Cohort Study.

BACKGROUND: Perioperative acute kidney injury is common. However, it is unclear whether this merely represents a transient increase in creatinine or has prognostic value. Therefore, the long-term clinical importance of mild postoperative acute kidney injury remains unclear. This study assessed whether adults who do and do not experience mild kidney injury after noncardiac surgery are at similar risk for long-term renal injury. METHODS: This study is a retrospective cohort analysis of adults having noncardiac surgery at the Cleveland Clinic who had preoperative, postoperative, and long-term (1 to 2 yr after surgery) plasma creatinine measurements. The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) initiative criteria. The primary analysis was for lack of association between postoperative kidney injury (stage I vs. no injury) and long-term renal injury. RESULTS: Among 15,621 patients analyzed, 3% had postoperative stage I kidney injury. Long-term renal outcomes were not similar in patients with and without postoperative stage I injury. Specifically, about 26% of patients with stage I postoperative kidney injury still had mild injury 1 to 2 yr later, and 11% had even more severe injury. A full third (37%) of patients with stage I kidney injury therefore had renal injury 1 to 2 yr after surgery. Patients with postoperative stage I injury had an estimated 2.4 times higher odds of having long-term renal dysfunction (KDIGO stage I, II, or III) compared with patients without postoperative kidney injury (odds ratio [95% CI] of 2.4 [2.0 to 3.0]) after adjustment for potential confounding factors. CONCLUSIONS: In adults recovering from noncardiac surgery, even small postoperative increases in plasma creatinine, corresponding to stage I kidney injury, are associated with renal dysfunction 1 to 2 yr after surgery. Even mild postoperative renal injury should therefore be considered a clinically important perioperative outcome.

Hypotension Prediction Index for Prevention of Hypotension during Moderate- to High-risk Noncardiac Surgery.

BACKGROUND: The Hypotension Prediction Index is a commercially available algorithm, based on arterial waveform features, that predicts hypotension defined as mean arterial pressure less than 65 mmHg for at least 1 min. We therefore tested the primary hypothesis that index guidance reduces the duration and severity of hypotension during noncardiac surgery. METHODS: We enrolled adults having moderate- or high-risk noncardiac surgery with invasive arterial pressure monitoring. Participating patients were randomized to hemodynamic management with or without index guidance. Clinicians caring for patients assigned to guidance were alerted when the index exceeded 85 (range, 0 to 100) and a treatment algorithm based on advanced hemodynamic parameters suggested vasopressor administration, fluid administration, inotrope administration, or observation. Primary outcome was the amount of hypotension, defined as time-weighted average mean arterial pressure less than 65 mmHg. Secondary outcomes were time-weighted mean pressures less than 60 and 55 mmHg. RESULTS: Among 214 enrolled patients, guidance was provided for 105 (49%) patients randomly assigned to the index guidance group. The median (first quartile, third quartile) time-weighted average mean arterial pressure less than 65 mmHg was 0.14 (0.03, 0.37) in guided patients versus 0.14 (0.03, 0.39) mmHg in unguided patients: median difference (95% CI) of 0 (-0.03 to 0.04), P = 0.757. Index guidance therefore did not reduce amount of hypotension less than 65 mmHg, nor did it reduce hypotension less than 60 or 55 mmHg. Post hoc, guidance was associated with less hypotension when analysis was restricted to episodes during which clinicians intervened. CONCLUSIONS: In this pilot trial, index guidance did not reduce the amount of intraoperative hypotension. Half of the alerts were not followed by treatment, presumably due to short warning time, complex treatment algorithm, or clinicians ignoring the alert. In the future we plan to use a lower index alert threshold and a simpler treatment algorithm that emphasizes prompt treatment.

Acute pain after serratus anterior plane or thoracic paravertebral blocks for video-assisted thoracoscopic surgery: A randomised trial.

BACKGROUND: Serratus anterior and paravertebral blocks can both be used for video-assisted thoracic surgery. However, serratus anterior blocks are easier to perform, and possibly safer. We therefore tested the primary hypothesis that serratus anterior plane blocks and thoracic paravertebral blocks provide comparable analgesia for video-assisted thoracic surgery. Secondarily, we tested the hypothesis that both blocks lengthen the time to onset of surgical pain and reduce the need for rescue tramadol. METHODS: Patients having video-assisted thoracic lobectomy or segmentectomy were randomly allocated to ultrasound-guided thoracic paravertebral blocks, n = 30; ultrasound-guided serratus anterior plane blocks, n = 30; or, general anaesthesia alone, n = 30. Visual analogue pain scores analogue pain scores at rest, during coughing and Prince-Henry pain scores were used to assess postoperative analgesia. Our primary analysis was noninferiority of serratus anterior blocks compared with paravertebral blocks. RESULTS: Baseline characteristics were comparable among the three groups. Two hours after surgery, the mean difference in visual analogue pain scores between the serratus anterior and paravertebral blocks was 0.0 (96.8% CI -0.4 to 0.3) cm at rest, -0.2 (-0.8 to 0.4) cm during coughing and -0.1(-0.5 to 0.3) for Prince-Henry pain scores. After 24 h, the mean difference was 0.0 (-0.7 to 0.8) cm at rest, 0.1 (-0.8 to 0.9) cm during coughing and 0.1(-0.4 to 0.6) for Prince-Henry pain scores. All differences were significantly noninferior. Time to onset of pain after surgery was 19 ±â€Š5 (SD) hours with serratus anterior blocks, 16 ±â€Š5 h with paravertebral blocks and 12 ±â€Š5 h with general anaesthesia. Anaesthesia with either block was associated with significantly less intra-operative propofol and sufentanil, reduced postoperative rescue analgesia (tramadol) and less postoperative nausea and vomiting compared with general anaesthesia alone. Patients with serratus anterior block had a significantly lower incidence of intra-operative hypotension and requirement for intra-operative vasopressor (3.4%), compared with general anaesthesia alone. Serratus anterior block took less time to perform than paravertebral block (5.1 ±â€Š1.1 min versus 10.1 ±â€Š2.9 min). CONCLUSION: Serratus anterior plane blocks, which are easier and quicker than paravertebral blocks, provide comparable analgesia in patients having video-assisted thoracic surgery. CLINICAL TRIAL NUMBER AND REGISTRY URL: ChiCTR1800017671; http://www.chictr.org.cn/hvshowproject.aspx?id=13510.

Beneficial effects of dantrolene on sepsis-induced diaphragmatic dysfunction are associated with downregulation of high-mobility group box 1 and calpain-caspase-3 proteolytic pathway.

BACKGROUND: Intracellular calcium overload is a major contributing factor to diaphragmatic dysfunction triggered by sepsis. In this study, the possible role of dantrolene, a ryanodine receptor inhibitor, in preventing the release of calcium from the sarcoplasmic reticulum in diaphragmatic dysfunction and weakness was explored. METHODS: A middle-grade severity sepsis rat model was established for the effects of treatment with dantrolene, on diaphragm harvested 24 h after cecal ligation and puncture (CLP), and analyzed using functional, histologic, and biomarker assays. RESULTS: It was found that in septic rats, treatment with dantrolene significantly improved the contractility, relaxation, and fatigue index of the diaphragm in a dose-dependent manner. The benefits are associated with improvement in ultrastructural changes of Z band integrity and myofilament arrangements along with increases both in the ratio of slow-twitch type composition. Moreover, dantrolene effectively inhibits the overexpression of high-mobility group box 1 and reduces the calpain-1-caspase-3 proteolytic activity. CONCLUSIONS: Dantrolene can effectively attenuate the dysfunction of diaphragm in septic rats; Furthermore, the beneficial effects were associated with downregulation of high-mobility group box 1 and calpain-1-caspase-3 proteolytic activity.

A ratiometric colorimetric detection of the folate receptor based on terminal protection of small-molecule-linked DNA.

Development of strategies for the sensitive and selective detection of the folate receptor (FR) that are simple and low cost is of great importance for assessing cancer therapeutics due to its crucial role in physiological, pharmacological and pathological processes. In this paper, gold nanoparticle (AuNP)-based novel ratiometric colorimetry for the detection of the folate receptor (FR) is proposed based on terminal protection of small-molecule-linked DNA. The single-stranded DNA (ssDNA) terminally tethered to folic acid (FA) is protected from degradation by exonuclease I (Exo I) when the FA moiety is bound to FR. The hybridization between FR-protected DNA and DNA-functionalized Au NPs generated a red-to-purple colour change, allowing the visual detection of FR. The detection limit of FR can be as low as 0.33 ng mL(-1) with the naked eye. It provides a promising strategy for visual detection of the binding event of FA to its protein receptor-FR with advantages such as simplicity, high selectivity, and a wide linear range.

One-strand oligonucleotide probe for fluorescent label-free "turn-on" detection of T4 polynucleotide kinase activity and its inhibition.

Thioflavin T (ThT), as one of the most exciting fluorogenic molecules, boasts the "molecular-rotor" ability to induce DNA sequences containing guanine repeats to fold into G-quadruplex structures. It has been demonstrated to sense this change by its remarkable fluorescence enhancement. In this work, taking T4 polynucleotide kinase (PNK) as a model, the ThT/G-quadruplex based platform and λexonuclease (λexo) cleavage reaction were combined to design a label-free "turn-on" strategy for fast, simple and accurate detection of T4 PNK activity and its inhibition. In the presence of T4 PNK, the designed thioflavin T based molecular beacon (TMB) DNA probe could be phosphorylated and then digested by the cleavage of λexo, releasing the G-quartets. These then bound to ThT to form ThT/G-quadruplexes with an obvious fluorescence generation, for the "turn-on" detection of T4 PNK. In comparison to traditional methods, the proposed TMB probe is convenient, requiring no sophisticated labeling and separation processes and displaying high analytical performance. It exhibits a satisfying detection result for the activity of T4 PNK with a low detection limit of 0.001 U mL(-1). This is not only meaningful for further research on disease-related biochemical processes, but also valuable for molecular-target therapies.

The efficacy of nasal administration of esketamine in patients having moderate-to-severe pain after preoperative CT-guided needle localization: a randomized, double-blind, placebo-controlled trial.

Background: Whether nasal administration of esketamine can provide effective analgesia is unclear in patients with acute pain after preoperative CT-guided needle localization. Methods: In this double-blind, randomized, placebo-controlled trial, patients were assigned to receive either nasal administration of esketamine (0.3 mg/kg or 0.5 mg/kg) or saline (identical in appearance to esketamine) when they had visual analog scale (VAS) pain scores >3/10 during deep breathing after preoperative CT-guided needle localization. The primary outcome was the percentage of patients with satisfactory pain relief, which was defined as VAS pain scores ≤3/10 measured 15 min after intranasal of esketamine or saline. Secondary outcomes included VAS measured following esketamine or saline, the incidence and cumulative dose of rescue hydromorphone use, and related adverse events. Results: A total of 90 patients were included in the final analysis. Following intranasal treatment, the percentage of patients with satisfactory pain relief was 16.7% (5/30) in the saline group, 56.7% (17/30) in the 0.3 mg/kg esketamine group, and 53.3% (16/30) in the 0.5 mg/kg esketamine group (p = 0.002). The median VAS during deep breathing was less after the intranasal administration of esketamine {median (IQR), 3 (3, 5) in 0.3 mg/kg or 0.5 mg/kg esketamine compared to the saline group [5 (4, 6)], p = 0.009}. The incidence of rescue hydromorphone use was detected less in the esketamine group compared to the saline group (43.3% in the 0.3 mg/kg esketamine group, 36.7% in the 0.5 mg/kg esketamine group, and 73.3% in the saline group, p = 0.010). The adverse events were similar among the three groups (p > 0.05). Conclusion: Intranasal administration of esketamine is easier and more effective in alleviating acute pain in patients after preoperative CT-guided needle localization without significant adverse effects.

Chemically Programmed Hydrogels for Spatiotemporal Modulation of the Cardiac Pathological Microenvironment.

After myocardial infarction (MI), sustained ischemic events induce pathological microenvironments characterized by ischemia-hypoxia, oxidative stress, inflammatory responses, matrix remodeling, and fibrous scarring. Conventional clinical therapies lack spatially targeted and temporally responsive modulation of the infarct microenvironment, leading to limited myocardial repair. Engineered hydrogels have a chemically programmed toolbox for minimally invasive localization of the pathological microenvironment and personalized responsive modulation over different pathological periods. Chemically programmed strategies for crosslinking interactions, interfacial binding, and topological microstructures in hydrogels enable minimally invasive implantation and in situ integration tailored to the myocardium. This enhances substance exchange and signal interactions within the infarcted microenvironment. Programmed responsive polymer networks, intelligent micro/nanoplatforms, and biological therapeutic cues contribute to the formation of microenvironment-modulated hydrogels with precise targeting, spatiotemporal control, and on-demand feedback. Therefore, this review summarizes the features of the MI microenvironment and chemically programmed schemes for hydrogels to conform, integrate, and modulate the cardiac pathological microenvironment. Chemically programmed strategies for oxygen-generating, antioxidant, anti-inflammatory, provascular, and electrointegrated hydrogels to stimulate iterative and translational cardiac tissue engineering are discussed.

An injectable exosome-loaded hyaluronic acid-polylysine hydrogel for cardiac repair via modulating oxidative stress and the inflammatory microenvironment.

Myocardial infarction (MI) is a serious cardiovascular disease with complex complications and high lethality. Currently, exosome (Exo) therapy has emerged as a promising treatment of ischemic MI due to its antioxidant, anti-inflammatory, and vascular abilities. However, traditional Exo delivery lacks spatiotemporal precision and targeting of microenvironment modulation, making it difficult to localize the lesion site for sustained effects. In this study, an injectable oxidized hyaluronic acid-polylysine (OHA-PL) hydrogel was developed to conveniently load adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) and improve their retention under physiological conditions. The OHA-PL@Exo hydrogel with high spatiotemporal precision is transplanted minimally invasively into the ischemic myocardium to scavenge intracellular and extracellular reactive oxygen species, regulate macrophage polarization, and attenuate inflammation in the early phase of MI. In addition, this synergistic microenvironment modulation can effectively reduce myocardial fibrosis and ventricular remodeling, promote angiogenesis, and restore electrophysiological function in the late stage of MI. Therefore, this hyaluronic acid-polylysine to deliver exosomes has become a promising therapeutic strategy for myocardial repair.

Chronological-Programmed Black Phosphorus Hydrogel for Responsive Modulation of the Pathological Microenvironment in Myocardial Infarction.

Electroactive hydrogels have garnered extensive interest as a promising approach to myocardial tissue engineering. However, the challenges of spatiotemporal-specific modulation of individual pathological processes and achieving nontoxic bioresorption still remain. Herein, inspired by the entire postinfarct pathological processes, an injectable conductive bioresorbable black phosphorus nanosheets (BPNSs)-loaded hydrogel (BHGD) was developed via reactive oxide species (ROS)-sensitive disulfide-bridge and photomediated cross-linking reaction. Significantly, the chronologically programmed BHGD hydrogel can achieve graded modulation during the inflammatory, proliferative, and maturation phases of myocardial infarction (MI). More details, during early infarction, the BHGD hydrogel can effectively reduce ROS levels in the MI area, inhibit cellular oxidative stress damage, and promote macrophage M2 polarization, creating a favorable environment for damaged myocardium repair. Meanwhile, the ROS-responsive structure can protect BPNSs from degradation and maintain good conductivity under MI microenvironments. Therefore, the BHGD hydrogel possesses tissue-matched modulus and conductivity in the MI area, facilitating cardiomyocyte maturation and electrical signal exchange, compensating for impaired electrical signaling, and promoting vascularization in infarcted areas in the maturation phase. More importantly, all components of the hydrogel degrade into nontoxic substances without adverse effects on vital organs. Overall, the presented BPNS-loaded hydrogel offers an expandable and safe option for clinical treatment of MI.

Hypoxemia in thoracoscopic lung resection surgery using a video double-lumen tube versus a conventional double-lumen tube: A propensity score-matched analysis.

Background: Malposition of the double-lumen tubes (DLTs) may lead to hypoxemia during one-lung ventilation (OLV). Video double-lumen tubes (VDLTs) enable continuous observation of DLT position and avoid displacement. We aimed to investigate whether VDLTs could reduce the incidence of hypoxemia during OLV compared with conventional double-lumen tubes (cDLT) in thoracoscopic lung resection surgery. Methods: This was a retrospective cohort study. Adult patients who underwent elective thoracoscopic lung resection surgery and required VDLTs or cDLTs for OLV at Shanghai Chest Hospital from January 2019 to May 2021 were included. The primary outcome was the incidence of hypoxemia during OLV between VDLT and cDLT. Secondary outcomes included bronchoscopy use, the degree of PaO2 decline, and arterial blood gas indices. Results: A total of 1,780 patients were finally analyzed in propensity score-matched cohorts (VDLT vs. cDLT 1:1 n = 890). The incidence of hypoxemia decreased from 6.5% (58/890) in cDLT group to 3.6% (32/890) in VDLT group (Relative Risk [RR]: 1.812, 95% CI: 1.19-2.76, p = 0.005). The use of bronchoscopy was reduced by 90% in VDLT group (VDLT 10.0% (89/890) vs. cDLT 100% (890/890), p < 0.001). PaO2 after OLV was 221 [136.0-325.0] mmHg in cDLT group compared to 234 [159.7-336.2] mmHg in VDLT group, p = 0.003. The percentage of PaO2 decline was 41.4 [15.4-61.9] % in cDLT group, while it was 37.7 [8.7-55.9] % in the VDLT group, p < 0.001. In patients who suffered from hypoxemia, there were no significant differences in arterial blood gas indices or the percentage of PaO2 decline. Conclusion: VDLTs reduce the incidence of hypoxemia and the use of bronchoscopy during OLV compared with cDLTs. VDLT may be a feasible option for thoracoscopic surgery.

Aggressive intraoperative warming and postoperative pulmonary complications in elderly patients recovering from esophageal cancer surgery: sub-analysis of a randomized trial.

Background: Elderly patients having esophagectomies often become hypothermic which may promote complications. We tested the hypothesis that aggressive warming to a core temperature of 37°C reduces postoperative pulmonary complications (PPCs) in elderly patients having esophageal cancer resections. Methods: This study was a pre-defined sub-study of a multi-center, parallel group, superiority trial (PROTECT). Patients aged >65 years and having elective radical resection of esophageal cancer in a single center were randomly allocated into either aggressive warming group (target intraoperative core temperatures of 37°C) or routine thermal management group (target intraoperative core temperatures of 35.5°C). The primary endpoint was the incidence of PPCs. Secondary endpoints included duration of chest tube drainage and other postoperative complications. Results: A total of 300 patients were included in the primary analysis. PPCs occurred in 27 (18%) of 150 patients in the aggressive warming group and 31 (21%) of 150 patients in the routine thermal management group. The relative risk (RR) of aggressive versus routine thermal management was 0.9 (95% CI: 0.5, 1.4; p = 0.56). The duration of chest drainage in patients assigned to aggressive warming was shorter than that assigned to routine thermal management: 4 (3, 5) days vs. 5 (4, 7) days; hazard ratio (HR) 1.4 [95% CI: 1.1, 1.7]; p = 0.001. Fewer aggressively warmed patients needed chest drainage for more than 5 days: 30/150 (20%) vs. 51/150 (34%); RR:0.6 (95% CI: 0.4, 0.9; p = 0.03). The incidence of other postoperative complications were similar between the two groups. Conclusion: Aggressive warming does not reduce the incidence of PPCs in elderly patients receiving esophagectomy. The duration of chest drainage was reduced by aggressive warming. But as a secondary analysis of a planned sub-group study, these results should be considered exploratory. Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=37099, ChiCTR1900022257.