Intensive Versus Standard Blood Pressure Management after Endovascular Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-analysis.

Prospective clinical studies on blood pressure (BP) management targets after endovascular therapy (EVT) for acute ischemic stroke (AIS) have recently been published. Our objective was to assess the impact on clinical outcomes of BP management guided by established systolic BP (SBP) targets within the first 24 hours after successful EVT. Four randomized controlled trials (RCTs) including 1556 participants across 5 SBP target settings identified from 5 databases up to September 6, 2023 were included in this systematic review and meta-analysis. All the intensive SBP target groups in these RCTs were combined to facilitate head-to-head comparisons. Patients receiving intensive SBP management had lower risk of 90-day functional independence as assessed by the modified Rankin scale score (relative risk [RR], 0.81; 95% confidence interval [CI], 0.72 to 0.91; I2, 12%), excellent outcomes (RR,0.86; 95% CI, 0.75 to 0.99; I2, 7%), favorable outcomes (RR, 0.85; 95% CI, 0.78 to 0.92; I2, 0%), and quality of life (standardized mean difference, -0.22; 95% CI, -0.35 to -0.10; I2,0%). There were no differences in the probability of any intracerebral hemorrhage (RR, 1.04; 95% CI, 0.92 to 1.19; I2,0%), symptomatic intracerebral hemorrhage (RR, 1.10; 95% CI, 0.76 to 1.60; I2, 0%), stroke-related death (RR, 1.16; 95% CI, 0.80 to 1.68; I2, 0%), or parenchymal hematoma (RR, 1.71; 95% CI, 0.74 to 3.98; I2, 47%) between SBP targets. This meta-analysis provides evidence from RCTs suggesting that intensive SBP control (target<160 mm Hg) may be detrimental to clinical outcomes in AIS patients with successful reperfusion after EVT.

Hypotensive Levels on Endoscopic Sinus Surgery Visibility: A Randomized Non-Inferiority Trial.

OBJECTIVE: Optimization of endoscopic sinus surgery (ESS) conditions is a common focus of interest for otolaryngologists and anesthesiologists. Relying on hypotension alone to achieve a bloodless field may not without risks. We sought to determine whether ESS is feasible in the context of moderate hypotension. METHODS: This randomized non-inferiority trial enrolled 96 adult patients who were to undergo ESS. The patients were divided into two groups: Controlled hypotension group (n = 48, MAP reduction to 55-65 mmHg, minimum of 60% of baseline blood pressure) or Individualized hypotension group (n = 48, MAP reduction to 75-80% of baseline blood pressure). All participants were placed in 10° reverse Trendelenburg position during ESS, and cottonoid patties dammed with epinephrine was recommended to clear the operative field of bleeding. The two groups were compared according to Boezaart grading scale (BS) score, estimated blood loss, blood loss rate, arterial lactate level and postoperative recovery. RESULTS: Both levels of intraoperative hypotension (62.2 ± 2.3 mmHg vs. 74.0 ± 2.8 mmHg) provided acceptable surgical conditions with no difference in mean BS scores [2.00 (1.88-2.33) vs. 2.00 (1.85-2.45), p = 0.926]. The 95% CI for median value differences in mean BS scores is lower than the preset non-inferiority margin. There were no differences in blood loss rate and estimated blood loss between two groups (p > 0.05) Postoperative arterial lactate and Ramsay sedation scores were significantly different between the two groups (p < 0.05). CONCLUSIONS: In ESS, both levels of intraoperative hypotension, combined with position adjustment and low-concentration adrenaline to constrict nasal mucosal blood vessels, provided acceptable surgical conditions. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:569-576, 2024.

Visible-Light-Switchable Tellurium-Based Chalcogen Bonding: Photocontrolled Anion Binding and Anion Abstraction Catalysis.

Exploring new noncovalent bonding motifs with reversibly tunable binding affinity is of fundamental importance in manipulating the properties and functions of supramolecular self-assembly systems and materials. Herein, for the first time, we demonstrate a unique visible-light-switchable telluro-triazole/triazolium-based chalcogen bonding (ChB) system in which the Te moieties are connected by azobenzene cores. The binding strengths between these azo-derived ChB receptors and the halide anions (Cl- , Br- ) could be reversibly regulated upon irradiation by visible light of different wavelengths. The cis-bidentate ChB receptors exhibit enhanced halide anion binding ability compared to the trans-monodentate receptors. In particular, the telluro-triazolium-based ChB receptor can achieve both high and significantly photoswitchable binding affinities for halide anions, which enable it to serve as an efficient photocontrolled organocatalyst for ChB-assisted halide abstraction in a Friedel-Crafts alkylation benchmark reaction.

Effect of Exercise Interventions on Health-Related Quality of Life in Patients with Fibromyalgia Syndrome: A Systematic Review and Network Meta-Analysis.

Objective: Several guidelines highlight the beneficial impact of exercise on the management of symptoms and health-related quality of life (HRQOL) in patients with fibromyalgia syndrome (FMS). However, few analyses have compared different types of exercise. We, therefore, intent to compare the effects of different exercise types on improving the overall HRQOL and typical symptoms in patients with FMS. Methods: Medline, Embase, the Cochrane Register of Clinical Trials, and NIH ClinicalTrials.gov were searched from inception to April 21, 2022. Randomized clinical trials (RCTs) were included to assess the impact of exercise intervention on health parameters in adult FMS patients. Data were extracted independently and a frequentist network meta-analyses (NMA) was performed to rank the effects of interventions according to P-scores. The NMA evidence certainty was assessed using the method recommended by Grading of Recommendations Assessment, Development, and Evaluation Working Group. Results: A total of 57 RCTs were identified, including 3319 participants, involving 9 interventions (7 types of exercise, 2 controls). Of all treatments compared with usual care in efficacy outcomes, Mind-body exercise was associated with the best HRQOL (SMD, -12.12; 95% CI, -15.79 to -8.45). On the other characteristic symptom dimensions, based on moderate quality evidence, sensorimotor training was associated with minimal pain scores compared with usual care (SMD, -1.81; 95% CI, -2.81 to -0.82), whole body vibration therapy was most promising for improving sleep quality (SMD, -6.95; 95% CI, -10.03 to -3.87), pool-based aerobic exercise was most likely to ease anxiety (SMD, -4.83; 95% CI, -7.47 to -2.19), and whole body vibration was most likely to improve depression (SMD, -10.44; 95% CI, -22.00 to 1.12). Conclusion: Mind-body exercise seems to be the most effective exercise to improve the overall HRQOL of patients with FMS. But at the same time, clinicians still need to develop individualized exercise plans for patients according to their symptoms and accessibility.

AKAP12 and RNF11 as Diagnostic Markers of Fibromyalgia and Their Correlation with Immune Infiltration.

Fibromyalgia (FM) is a chronic nonarticular rheumatic disease mainly characterized by diffuse disseminated skeletal muscle pain, with varied symptoms including anxiety, sleep disturbance, and fatigue. Due to its unknown etiology and pathogenesis, FM is easily ignored in clinical practice, resulting in unclear diagnosis and difficult treatment. This study is aimed at investigating whether AKAP12 and RNF11 can be used as biomarkers for the diagnosis of FM and at determining their correlation with immune infiltration. The FM dataset in Gene Expression Omnibus (GEO) database was downloaded and was randomly divided into the training and test sets. Differentially expressed genes (DEGs) were screened, and functional correlation analysis was performed. Diagnostic markers of FM were screened and validated by random forest (RF). The least absolute shrinkage and selection operator (LASSO) logistic regression algorithm was then used to evaluate immune cell infiltration in the FM patients' peripheral blood. Finally, Spearman's rank correlation analysis was used to identify correlation between the diagnostic indexes and immune cell infiltration. A total of 69 DEGs were selected. Results indicated that AKAP12 and RNF11 can be used as diagnostic markers of FM, and CD8 + T cells might contribute in the pathogenesis of FM. In addition, AKAP12 was positively correlated with CD8 + T cells, while RNF11 was negatively correlated with CD8 + T cells. In conclusion, AKAP12 and RNF11 can be used as diagnostic indicators of FM, and CD8 + T cells may be involved in the occurrence and development of FM.

Evaluation of the reliability of the upper lip bite test and the modified mallampati test in predicting difficult intubation under direct laryngoscopy in apparently normal patients: a prospective observational clinical study.

BACKGROUND AND AIMS: Difficult endotracheal intubation is one of the most challenging operations in anesthesia. How to better predict difficult airway and make corresponding preparations to reduce the occurrence of accidents is a difficult task faced by anesthesiologists every day. This study decide to evaluate the value of the Upper Lip Bite Test (ULBT) and the Modified Mallampati Test (MMT) in predicting difficult intubation under direct laryngoscopy and find out the most intuitive and simple method to predict difficult intubation under direct laryngoscopy in apparently normal patients. PATIENTS AND METHODS: This descriptive-analytical study was performed on 450 patients for elective surgery under general anesthesia requiring endotracheal intubation. The ULBT and MMT grading were evaluated preoperatively and Cormack and Lehane's (CL) classification was recorded on the day of surgery during intubation under direct laryngoscopy. The accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR), Youden index and area under ROC curve of ULBT and MMT respectively and in combination were calculated and compared. And the consistency between the total scores of ULBT and MMT combined in different ways and CL grading was counted. RESULTS: Of the 450 patients, 69 (15.3%) were classified as difficult cases of direct laryngoscopy. The accuracy, sensitivity, specificity, PPV and NPV of ULBT were 81.33, 11.59, 93.96, 25.81, 85.44%; and those the corresponding values for MMT were 66.22, 62.32, 69.29, 26.88 and 91.03%. A combination of ULBT and MMT did not improve the sensitivity in the sample tested. The combined total scores of ULBT and MMT in both ways were less consistent with CL grading in predicting difficult intubation under direct laryngoscopy. CONCLUSION: Based on findings of current study, we conclude that ULBT and MMT for difficult intubation have only poor to moderate discriminative power when used alone. The combination of the two tests in fractional form is also not a good predictor of difficult intubation under direct laryngoscopy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100052987, Registered 07 November 2021, http://www.chictr.org.cn.

Comparison of the Effectiveness of Various Drug Interventions to Prevent Etomidate-Induced Myoclonus: A Bayesian Network Meta-Analysis.

Background: Myoclonic movement is a very common but undesirable phenomenon during the induction of general anesthesia using etomidate. Such movement may cause unnecessary problems. Currently, there is an increasing number of drugs for preventing etomidate-induced myoclonus (EM). However, direct comparisons of various drugs are lacking, and this interferes with clinical decision-making. Our network meta-analysis (NMA) aimed to compare the efficacy of different drugs for the prevention of moderate-to-severe general myoclonus. Methods: Using several biomedical databases, randomized controlled trials (RCTs) published in English from inception to August 22, 2021 were searched. Among the various interventions, we selected nine types of intervention drugs (dexmedetomidine, etomidate, lidocaine, NMDA receptor antagonist, κ opioid receptor agonist, µ opioid receptor agonist, muscle relaxant, gabapentin, and midazolam) for comparison, according to the number of studies. Bayesian NMA was performed using STATA16 and R softwares. The relative risk of EM was assessed using risk ratios (RRs) and the corresponding 95% confidence intervals (CI). Results: A total of 31 RCTs (3209 patients) were included. NMA results showed that, compared with a placebo, etomidate (RR 4.0, 95%CI 2.1-7.8), κ opioid receptor agonist (RR 2.9, 95%CI 1.9-4.6), µ opioid receptor agonist (RR 3.1, 95%CI 2.3-4.3), NMDA receptor antagonist (RR 1.7, 95%CI 1.0-2.8), dexmedetomidine (RR 2.4, 95%CI 1.5-3.9), lidocaine (RR 2.1, 95%CI 1.2-3.9), and midazolam (RR 2.2, 95%CI 1.5-3.2) can significantly reduce the risk of EM. In contrast, the effects of muscle relaxants (RR 2.1, 95%CI 0.81-5.3) and gabapentin (RR 2.8, 95%CI 0.92-9.3) were inconclusive. Further subgroup analyses showed that preoperative low-dose etomidate, µ-opioid receptor agonist, and κ-opioid receptor agonist were significantly better than other interventions in the prevention of moderate to severe EM. Conclusion: Preoperative use of small doses of etomidate or opioids may be the most effective way to avoid EM, especially moderate and severe EM, which makes anesthesia induction safer, more stable, and aligns better with the requirements of comfortable medicine. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], [CRD4202127706].

Photo-Controlled Macroscopic Self-Assembly Based on Photo-Switchable Hetero-Complementary Quadruple Hydrogen Bonds.

A photo-switchable hetero-complementary quadruple H-bonding array, which consists of an azobenzene-derived ureidopyrimidinone (UPy) module (Azo-UPy) and a nonphotoactive diamidonaphthyridine (DAN) derivative (Napy-1), is constructed based on a reversible photo-locking approach. Upon UV (390 nm)/Vis (460 nm) light irradiations, photo-switchable quadruple H-bonded dimerization between Azo-UPy and Napy-1 can be achieved with exhibiting 4.8×104 -fold differences in binding strength (ON/OFF ratios). Furthermore, smart polymeric gels with unique photo-controlled macroscopic self-assembly behavior can be fabricated by introducing such quadruple H-bonding array as photo-regulable noncovalent interfacial connections.

The different functions of short and long thymic stromal lymphopoietin isoforms in autophagy-mediated asthmatic airway inflammation and remodeling.

Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling as well as hyper-responsiveness. Thymic stromal lymphopoietin (TSLP), which is a crucial inflammatory cytokine in immune homeostasis, consists of two isoforms, the long isoform lfTSLP and short isoform sfTSLP. The lfTSLP promotes inflammation and plays a pivotal role in asthma pathogenesis, while sfTSLP had been reported to have anti-asthma effects. Experiments have shown that lfTSLP could induce autophagy in hepatocytes. It is unknown whether lfTSLP or sfTSLP could influence autophagy and affect the progression of asthma. Using house dust mite (HDM)-stimulated airway smooth muscle cells as an in vitro model and HDM-induced asthma mice as in vivo model, we found that lfTSLP could induce autophagy and remodeling, while sfTSLP has the reverse effect. Strikingly, sfTSLP treatment in vivo reversed HDM-mediated activation of inflammation and airway remodeling, partly determined by autophagy change. These findings may help us understand the function of TSLP isoforms in the pathogenesis of asthma, and they support the use of drugs targeting sfTSLP and TSLP for asthma treatment.

Towards photoswitchable quadruple hydrogen bonds via a reversible "photolocking" strategy for photocontrolled self-assembly.

Developing new photoswitchable noncovalent interaction motifs with controllable bonding affinity is crucial for the construction of photoresponsive supramolecular systems and materials. Here we describe a unique "photolocking" strategy for realizing photoswitchable control of quadruple hydrogen-bonding interactions on the basis of modifying the ureidopyrimidinone (UPy) module with an ortho-ester substituted azobenzene unit as the "photo-lock". Upon light irradiation, the obtained Azo-UPy motif is capable of unlocking/locking the partial H-bonding sites of the UPy unit, leading to photoswitching between homo- and heteroquadruple hydrogen-bonded dimers, which has been further applied for the fabrication of novel tunable hydrogen bonded supramolecular systems. This "photolocking" strategy appears to be broadly applicable in the rational design and construction of other H-bonding motifs with sufficiently photoswitchable noncovalent interactions.

A Visible-Light-Induced Dynamic Mechanical Bond as a Linkage for Dynamic Materials.

Exploring dynamic bonds and their applications in fabricating dynamic materials has received great attention. A photoinduced [2]rotaxane-based dynamic mechanical bond (DMB) features visible-light-triggered dynamic bonding behavior that is essentially distinguished from conventional dynamic chemical bonds. In this DMB, a photoisomerizable ortho-fluoroazobenzene unit is introduced as a steric-controllable stopper, the visible-light-induced dynamic wagging movement of which enables the photoregulated threading of the macrocycle. This allows reversible in situ de-/reforming of the mechanical bond without involving dynamic chemical linkage. The DMB-cross-linked polymeric gel shows interesting photoinduced degradation behavior upon visible light irradiation. Benefiting from the distinctive dual dynamic nature of reversible bonding behavior and mechanical interlocked structure, this DMB is expected to serve as a new type of dynamic bond that can be applied in designing dynamic soft materials.

Toward bidirectional photoswitchable colored photochromic molecules with visible light stability.

Photochromic [2]rotaxanes with bidirectional photoswitchability were fabricated, whose colored states exhibit remarkable visible-light and thermal stabilities as revealed by systematically spectroscopic investigations.

Tunable Water-Soluble Supramolecular Polymers by Visible-Light-Regulated Host-Guest Interactions.

The development of artificial self-assembling systems with dynamic photo-regulation features in aqueous solutions has drawn great attention owing to the potential applications in fabricating elaborate biological materials. Here we demonstrate the fabrication of water-soluble cucurbit[8]uril (CB[8])-mediated supramolecular polymers by connecting the fluorinated azobenzene (FAB) containing monomers through host-enhanced heteroternary π-π stacking interactions. Benefiting from the unique visible-light-induced E→Z photoisomerization of the FAB photochromophores, the encapsulation behaviors between the CB[8] macrocycle and the monomers could be regulated upon visible light irradiation, resulting in the depolymerization of such CB[8]-mediated supramolecular polymers.

Reversible conversion between a pleated oligo-tetrathiafulvalene radical foldamer and folded donor-acceptor [3]pseudorotaxane under redox conditions.

Linear tetrathiafulvalene (TTF) oligomers were synthesized, which could not only form a pleated TTF˙+ radical cation foldamer under oxidation conditions, but also interlocked with CBPQT4+ to form folded donor-acceptor [3]pseudorotaxane in the neutral state of TTF. Moreover, switchable transformation between these two folded supramolecular structures was achieved under the alternative regulation of the redox states of TTF units.

Dual absorption spectral changes by light-triggered shuttling in bistable [2]rotaxanes with non-destructive readout.

Light-triggered photoisomerization of the azobenzene (AB) unit in bistable [2]rotaxanes can cause the shuttling of the macrocycle on the dumbbell, resulting in distinctive dual spectral variation characteristics: (1) the spectral change of the photochromic unit and (2) the variation of the charge-transfer band. By employing the CT bond region as an output signal, non-destructive readout of optical information could be achieved.

The third orthogonal dynamic covalent bond.

Orthogonal dynamic covalent bonds are of interest for the construction of functional systems. The orthogonality of disulfide and hydrazone exchange under basic and acidic conditions, respectively, is well established. However, the integration of boronate esters as the third bond has failed so far because they exchanged too easily, especially under hydrazone exchange conditions. In this report, a collection of bioinspired catechols derived from adhesive natural products from cyanobacteria is screened with phenylboronic acids with proximal alcohols (benzoboroxoles), amines and fluorines to identify the least labile boronate esters. Moreover, Kool's 2-aminophenol catalysts are introduced to selectively accelerate hydrazone exchange without disturbing sufficiently inert boronate esters. Based on these results, we identified three different conditions to selectively exchange disulfides, hydrazones and boronate esters, that is to demonstrate the existence of three orthogonal dynamic covalent bonds. Moreover, their compatibility with functional systems is confirmed by successful hydrazone exchange in multicomponent surface architectures in the presence of intact boronate esters and disulfides.

A Deep Cavitand Templates Lactam Formation in Water.

Cyclization reactions are common processes in organic chemistry and show familiar patterns of reaction rates vs ring size. While the details vary with the nature of bond being made and the number of unsaturated atoms, small rings typically form quickly despite angle strain, medium size rings form very slowly due to internal strains, and large rings form slowly (when they form at all) because fewer and less probable conformations bring the ends of the substrate together. High dilution is commonly used to slow the competing bi- and higher molecular processes. Here we apply cavitands to the formation of medium size lactams from ω-amino acids in aqueous (D2O) solution. The cavitands bind the amino acids in folded conformations that favor cyclization by bringing the ends closer together. Yields of a 12-membered lactam are improved 4.1-fold and 13-membered lactam 2.8-fold by the cavitand template. The results open possibilities for moving organic reactions into water even when the processes involve dehydration.

The effects of hexafluoroisopropanol on guest binding by water-soluble capsule and cavitand hosts.

Encapsulation of amphiphilic guests in a water-soluble cavitand is enhanced by the addition of hexafluoroisopropanol (HFIP). While binding of n-alkanes in cavitands in HFIP/D2O mixtures was similar to that observed in 100% D2O, the binding of guests with terminal polar groups was quite different. Several α,ω-bolaamphiphiles: alkyldiols (C10-C12), a dinitrile (C14) and a diacid (C16) became encapsulated in HFIP/D2O solutions. As little as 15% HFIP v/v in D2O moves the guest from cavitand to the dimeric capsule. The unusual binding of polar functional groups inside the confined space is deduced from NMR COSY spectra and supported by DFT calculations. Alkane guests are also encapsulated in 100% HFIP.

Colorful surface architectures with three different types of dynamic covalent bonds: integration of anthocyanins, tritylium ions and flavins.

Although they combine the best of covalent and non-covalent bonds, dynamic covalent bonds are usually not used together. Building on pioneering examples for functional systems with two orthogonal dynamic covalent bonds, we herein elaborate on multicomponent surface architectures that operate with three different types of dynamic covalent bonds. Disulfide exchange under basic conditions is used to grow single π stacks directly on oxide surfaces, hydrazone exchange under acidic conditions to add a second string or stack, and boronic-ester exchange under neutral conditions to build the third one. In this study, we show that this synthetic approach to complex systems provides access to emergent properties, as exemplified with ordered stacks of anthocyanins, pyrocatchol violet and riboflavins. The integration of anthocyanins, the central component of the pigments of plant flowers, is interesting to protect the blue flavylium cation against deprotonation, deplanarization and degradation. The integration of pyrocatchol violet is of interest to stabilize the blue, disfavored tritylium cation. The red riboflavin stacks are attractive because they generate high photocurrent. These colorful examples hint at the potential of synthetic methods that use three different types of dynamic covalent bonds in concert to build complex systems with emergent properties.

Complex Functional Systems with Three Different Types of Dynamic Covalent Bonds.

Multicomponent surface architectures are introduced that operate with three different dynamic covalent bonds. Disulfide exchange under basic conditions accounts for the growth of π stacks on solid surfaces. Hydrazone exchange under acidic conditions is used to add a second coaxial string or stack, and boronic ester exchange under neutral conditions is used to co-align a third one. The newly introduced boronic ester exchange chemistry is compatible with stack and string exchange without interference from the orthogonal hydrazone and disulfide exchange. The functional relevance of surface architectures with three different dynamic covalent bonds is exemplified with the detection of polyphenol natural products, such as epigallocatechin gallate, in competition experiments with alizarin red. These results describe synthetic strategies to create functional systems of unprecedented sophistication with regard to dynamic covalent chemistry.