Pharmacokinetics and pharmacodynamics of PTC518, an oral huntingtin lowering splicing modifier: A first-in-human study.

AIMS: PTC518 is an orally administered, centrally and peripherally distributed huntingtin (HTT) pre-mRNA splicing modifier being developed for the treatment of Huntington's disease (HD) for which there is a high unmet medical need as there are currently no approved disease-modifying treatments. This first-in-human study investigated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PTC518 in healthy volunteers. METHODS: This phase 1, single-centre, randomized study in 77 healthy male and female volunteers evaluated the safety and tolerability and PK of PTC518 following single ascending doses and multiple ascending doses, PD as assessed by HTT mRNA and HTT protein levels after single and multiple doses, and food effects. RESULTS: PTC518 demonstrated a favourable safety profile. The majority of treatment-emergent adverse events were mild and transient. PTC518 Tmax was reached at 6-7 h and the terminal T1/2 was 54.0-75.3 h following a single oral dose. Exposure increased with dose though less than dose proportionally. The PTC518 concentrations in cerebrospinal fluid were approximately 2.6-fold higher than the unbound free-drug concentrations in plasma. A significant dose-dependent reduction of up to approximately 60% in HTT mRNA and a significant dose-dependent, time-dependent and sustained reduction in HTT protein levels of up to 35% were observed after PTC518 treatment. CONCLUSIONS: PTC518 was well tolerated, and proof of mechanism of this novel splicing modifier was demonstrated by the dose-dependent decrease in systemic HTT mRNA and HTT protein levels. Results from this first-in-human study support further studies in patients with HD and demonstrate the potential for PTC518 as a breakthrough treatment for HD.

Progression of gestational diabetes mellitus to pregnancy-associated fulminant type 1 diabetes: a case report.

Background: Pregnancy-associated fulminant type 1 diabetes (PF) occurs during pregnancy or within 2 weeks of delivery. Although it occurs infrequently, it is associated with high fetal mortality rate. Few studies have examined whether PF is associated with gestational diabetes mellitus (GDM). Case Description: A 29-year-old woman diagnosed with GDM at 24 weeks of gestation developed a fever, sore throat, nausea and vomiting at 29 weeks of gestation. Ketoacidosis was considered based on her blood ketone and glucose levels and the results of a blood gas analysis. Since the patient's islet function declined rapidly, fluid replacement, insulin therapy, and other treatments were administered. The patient was ultimately diagnosed with PF, and has required ongoing insulin therapy. She delivered a healthy baby girl by elective cesarean section at 37-week gestation. Her blood glucose has been satisfactorily controlled over the 12 months since her acute presentation. Conclusions: PF is characterized by poor maternal and infant outcomes and a high stillbirth rate. Blood glucose should be regularly monitored in pregnant women with GDM. A sudden increase in blood glucose may indicate the possibility of PF, which needs to be managed in a timely manner to avoid adverse pregnancy outcomes.

The predictive value of GLIM criteria on clinical outcomes and responses to nutritional support in patients with neurocritical illnesses.

Neurocritically ill patients frequently exhibit coma, gastroparesis, and intense catabolism, leading to an increased risk of malnutrition. The Global Leadership Initiative on Malnutrition (GLIM) criteria for the diagnosis of malnutrition was created to achieve a consistent malnutrition diagnosis across diverse populations. This study aimed to validate the concurrent and predictive validity of GLIM criteria in patients with neurocritical illnesses. A total of 135 participants were followed from admission to the neurocritical unit (NCU) until discharge. Comparing GLIM criteria to the Subjective Global Assessment (SGA), sensitivity was 0.95 and specificity was 0.69. Predictive validity of GLIM criteria was assessed using a composite adverse clinical outcome, comprising mortality and various major complications. Adjusted hazard ratios for moderate and severe malnutrition were 2.86 (95% CI 1.45-5.67) and 3.88 (95% CI 1.51-9.94), respectively. Changes in indicators of nutritional status, including skeletal muscle mass and abdominal fat mass, within 7 days of admission were obtained for 61 participants to validate the predictive capability of the GLIM criteria for the patients' response of standardized nutritional support. The GLIM criteria have a statistically significant predictive validity on changes in rectus femoris muscle thickness and midarm muscle circumference. In conclusion, the GLIM criteria demonstrate high sensitivity for diagnosing malnutrition in neurocritically ill patients and exhibit good predictive validity.

The search for optimal nocturnal diurnal heart rate Index targets in ICU patients: a retrospective observational study from large ICU database.

Background: Circadian rhythms play a crucial role in cardiovascular health, with the nocturnal diurnal heart rate index (NDHRI) reflecting significant circadian variations. However, the optimal NDHRI target in Intensive Care Unit (ICU) patients remains undefined. This study aims to establish an evidence-based NDHRI target range and assess its association with mortality. Methods: Data from the eICU Collaborative Research Database (n = 32,412) were analyzed. NDHRI was calculated by dividing cumulative nighttime heart rate area by daytime area. Generalized additive models (GAMs) explored the non-linear relationship between mean NDHRI and mortality, adjusting for confounders. Subgroup analyses were conducted based on ethnicity, ICU type, and comorbidities. Results: A U-shaped association was observed between hospital mortality and mean NDHRI (P < 0.001). The optimal NDHRI range (40.0%-45.0%) demonstrated the lowest mortality rates. The duration spent within this range correlated inversely with mortality (P < 0.001). Subgroup analyses consistently supported these findings across diverse patient profiles. Conclusions: Our findings suggest an association between maintaining NDHRI within the 40.0%-45.0% range and lower mortality rates in critically ill patients, highlighting the potential utility of monitoring circadian heart rate variations in the ICU. Further research and future randomized controlled trials are essential to confirm causality and should consider this NDHRI range as a pivotal reference target.

Oxidation enhances the toxicity of polyethylene microplastics to mouse eye: Perspective from in vitro and in vivo.

Microplastics (MPs) are ubiquitously dispersed in the environment, and undergoing the process of oxidation that alters their physical and chemical properties. Eyes, which directly interface with the external milieu, inevitably encounter MPs. Nonetheless, the ophthalmic toxicity of MPs towards organisms remains unclear. In this study, primary mouse corneal epithelial cells (MCECs), C57BL/6 mice, and CX3CrlGFP/+ mice were utilized to evaluate the toxicity and differences between oxidized low-density polyethylene MPs (modified-MPs) and low-density polyethylene MPs (virgin-MPs) on eyes. The results manifested that virgin-MPs and modified-MPs could be endocytosed by primary MCECs, resulting in a range of cellular damage. Furthermore, they could diminish tear secretion, increase intraocular pressure, and could be internalized into cornea and retina in mice, instigating a series of detrimental reactions. Importantly, modified-MPs exhibited heightened toxicity towards mouse eyes, seemingly due to oxidation enhances the interaction between virgin-MPs/modified-MPs and tissues/cells, and leading to the release of toxic substances increased. In conclusion, our discoveries demonstrate that oxidation exacerbates the harm of virgin-MPs to eyes, and are of great significance for evaluating the risk of MPs to ocular health.

Long-term cost-effectiveness analysis of rugby fans in training-New Zealand: a body weight reduction programme for males.

OBJECTIVES: We sought to extrapolate the long-term costs and clinical impacts attributed to the rugby fans in training-New Zealand (RUFIT-NZ) trial in Aotearoa, New Zealand. DESIGN: A modelled cost-effectiveness analysis using efficacy data from RUFIT-NZ was conducted from the Aotearoa New Zealand healthcare perspective. SETTING: A Markov cohort model was constructed with a lifetime time horizon. The model simulated events of myocardial infarction (MI), stroke and type 2 diabetes mellitus (T2DM) occurring among a hypothetical cohort of 10 000 individuals receiving either the RUFIT-NZ intervention or no intervention. Efficacy data were based on the RUFIT-NZ trial, and the latest Global Burden of Disease study was used to extrapolate the impact of body weight reduction on clinical outcomes of T2DM, MI or stroke. Cost and utility data were drawn from the RUFIT-NZ trial and published sources. PRIMARY OUTCOME MEASURES: The incremental cost-effectiveness ratio (ICER). RESULTS: Over a lifetime time horizon, participants in the RUFIT-NZ intervention gained 0.02 (discounted) quality-adjusted life years (QALYs) at an additional cost of NZ$863, relative to no intervention. The estimated ICER was NZ$49 515 per QALY gained (discounted), which is above the arbitrary willingness-to-pay threshold of NZ$45 000 per QALY. Sensitivity analyses supported the robustness of these findings. CONCLUSIONS: RUFIT-NZ was associated with a reduction in cardiovascular and endocrine events for overweight and obese males. However, based on conservative assumptions, RUFIT-NZ was unlikely to be cost-effective from a healthcare system perspective. TRIAL REGISTRATION NUMBER: ACTRN12619000069156.

Methods for Measuring and Valuing Informal Care: A Systematic Review and Meta-Analysis in Stroke.

OBJECTIVES: To accurately capture informal care in healthcare evaluations, rigorous approaches are required to measure and value this important care component. In this systematic review and meta-analysis, we intended to summarize the current methods of measuring and valuing informal care costs in healthcare evaluations (full and partial healthcare evaluations, including cost of illness and cost analysis) in stroke. METHODS: A systematic search was conducted in MEDLINE, Embase, EconLit, and CINAHL. We used EndNote 20, Research Screener, and Covidence platforms for screening and data extraction. A meta-analysis was performed on informal care hours, and a subgroup meta-analysis was conducted based on stroke severity. RESULTS: A total of 31 articles were included in the qualitative synthesis. There was variation among the studies in the informal care measurement and valuation approaches. The meta-analysis of studies where data on informal care hours were available showed an estimate of informal care hours of 25.76 per week (95% CI 13.36-38.16) with a high heterogeneity (I2 = 99.97%). The overall risk of bias in the studies was assessed as low. CONCLUSIONS: Standardizing the measurement and valuation of informal care costs is essential for improving the consistency and comparability of economic evaluations. Pilot studies that incorporate standardized informal care cost valuation methods can help identify any practical challenges and capture the impact of informal care more accurately.

Association of cardiovascular events with central systolic blood pressure: A systemic review and meta-analysis.

Central blood pressure confers cardiovascular risk prediction ability, but whether the association between central systolic blood pressure (cSBP) and cardiovascular endpoints is independent of peripheral systolic blood pressure (pSBP) remains controversial. This systematic review and meta-analysis aim to investigate the associations between cSBP and cardiovascular endpoints in models including and excluding pSBP, respectively. Observational studies assessing the risk of composite cardiovascular endpoints with baseline cSBP were searched in PubMed, Embase, Scopus, Web of Science, and Cochrane Library to May 31, 2022. Risk of bias was assessed by the Newcastle-Ottawa Quality Assessment Scale, and random-effects models were used to pool estimates. Finally, 48 200 participants from 19 studies with a mean age of 59.0 ± 6.9 years were included. Per 10 mmHg increase of cSBP was associated with higher risk of composite cardiovascular outcomes (risk ratio [RR]: 1.14 [95%CI 1.08-1.19]) and cardiovascular death (RR: 1.18 [95%CI 1.08-1.30]), and the associations still existed after adjusting for pSBP (RR: 1.13 [95%CI 1.05-1.21] for composite cardiovascular endpoints; RR: 1.25 [95%CI 1.09-1.43] for cardiovascular death). In pSBP-unadjusted studies, increased cSBP was also associated with higher risk of all-cause mortality and stroke, but not in the pSBP-adjusted studies. Both cSBP and pSBP were similarly significantly associated with composite cardiovascular endpoints in models containing them separately and simultaneously. cSBP was significantly associated with cardiovascular events, independently of pSBP. Central or peripheral SBP could supplement cardiovascular risk assessment besides each other.

The Human Ganglioside Interactome in Live Cells Revealed Using Clickable Photoaffinity Ganglioside Probes.

Gangliosides, sialic acid bearing glycosphingolipids, are components of the outer leaflet of plasma membranes of all vertebrate cells. They contribute to cell regulation by interacting with proteins in their own membranes (cis) or their extracellular milieu (trans). As amphipathic membrane constituents, gangliosides present challenges for identifying their ganglioside protein interactome. To meet these challenges, we synthesized bifunctional clickable photoaffinity gangliosides, delivered them to plasma membranes of cultured cells, then captured and identified their interactomes using proteomic mass spectrometry. Installing probes on ganglioside lipid and glycan moieties, we captured cis and trans ganglioside-protein interactions. Ganglioside interactomes varied with the ganglioside structure, cell type, and site of the probe (lipid or glycan). Gene ontology revealed that gangliosides engage with transmembrane transporters and cell adhesion proteins including integrins, cadherins, and laminins. The approach developed is applicable to other gangliosides and cell types, promising to provide insights into molecular and cellular regulation by gangliosides.

m6A-methylated Lonp1 drives mitochondrial proteostasis stress to induce testicular pyroptosis upon environmental cadmium exposure.

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.

Applications and characterization of anti-browning enzymatically modified potato starch (EPS) film associated with chitosan (CTS)/L-Cys/citric acid (CA) on fresh-cut potato slices.

This study explores the influence of incorporating L-cysteine (L-Cys), chitosan (CTS), and citric acid (CA) on the enzymatic modification of potato starch (EPS) films to enhance anti-browning properties. Four types of EPS composite films were evaluated for preserving fresh-cut potato slices at low temperatures to inhibit browning. Their thermal, physiochemical, mechanical, and digestibility properties were assessed. Results indicate that the addition of CTS, CA, and L-Cys improved the anti-browning activity of the EPS films by increasing film thickness and reducing water vapor permeability (WVP), oxygen transmission rate (OTR), ultraviolet (UV) transmittance, and tensile strength (TS). Furthermore, these additives improved the film's microstructure, resulting in reinforced intermolecular interactions, increased elongation at break, heightened crystallinity, enhanced thermal stability, and favorable gastrointestinal digestibility. Overall, EPS/CTS/L-Cys/CA composite films show promise as edible packaging materials with effective anti-browning properties.

Clinical characteristics of systemic lupus erythematosus patients with adrenal hemorrhage.

INTRODUCTION: Adrenal hemorrhage (AH) is a rare condition and severe cases can lead to acute adrenal insufficiency with potentially life-threatening consequences. AH can be caused by a variety of etiologic factors, including systemic lupus erythematosus and antiphospholipid syndrome (APS). The early identification and treatment of these patients improves their prognosis. OBJECTIVE: The aims of this study were to analyze and summarize the clinical characteristics of systemic lupus erythematosus patients with AH. METHODS: The clinical characteristics of 6 systemic lupus erythematosus patients complicated with AH admitted to Peking Union Medical College Hospital and Beijing Shijitan Hospital from May 2004 to April 2022 were retrospectively analyzed. RESULTS: The diagnosis of AH was based on computed tomography (CT) findings. Two patients had bilateral lesions, and the other 4 patients had unilateral lesions. The symptoms of adrenal insufficiency were observed in 2 patients. The frequent presenting symptoms were abdominal pain, lower abdominal distension, vomiting, weakness, fever, arthrodynia, and skin rash. Four patients had APS. Five patients (4 patients with APS and 1 patient without APS) had thromboembolic events. All patients received glucocorticoid and immunosuppressant therapy. Five patients were treated with anticoagulant therapy. Follow-up imaging examinations showed a partial or total regression of the lesions after treatment. CONCLUSIONS: In the proper clinical setting, having high clinical suspicion for AH, early diagnosis and timely management is crucial to avoid life-threatening adrenal insufficiency. Key Points • AH is a rare condition and severe cases may lead to death. It can be caused by a variety of etiologic factors, including SLE. • In patients with SLE, especially combined with APS, if they complain of abdominal pain, particularly when common gastrointestinal involvement is difficult to explain, a high index of clinical suspicion is needed for the diagnosis of AH. • Early identification of AH in SLE patients can improve their prognosis.

Optimal Nonparametric Inference with Two-Scale Distributional Nearest Neighbors.

The weighted nearest neighbors (WNN) estimator has been popularly used as a flexible and easy-to-implement nonparametric tool for mean regression estimation. The bagging technique is an elegant way to form WNN estimators with weights automatically generated to the nearest neighbors (Steele, 2009; Biau et al., 2010); we name the resulting estimator as the distributional nearest neighbors (DNN) for easy reference. Yet, there is a lack of distributional results for such estimator, limiting its application to statistical inference. Moreover, when the mean regression function has higher-order smoothness, DNN does not achieve the optimal nonparametric convergence rate, mainly because of the bias issue. In this work, we provide an in-depth technical analysis of the DNN, based on which we suggest a bias reduction approach for the DNN estimator by linearly combining two DNN estimators with different subsampling scales, resulting in the novel two-scale DNN (TDNN) estimator. The two-scale DNN estimator has an equivalent representation of WNN with weights admitting explicit forms and some being negative. We prove that, thanks to the use of negative weights, the two-scale DNN estimator enjoys the optimal nonparametric rate of convergence in estimating the regression function under the fourth-order smoothness condition. We further go beyond estimation and establish that the DNN and two-scale DNN are both asymptotically normal as the subsampling scales and sample size diverge to infinity. For the practical implementation, we also provide variance estimators and a distribution estimator using the jackknife and bootstrap techniques for the two-scale DNN. These estimators can be exploited for constructing valid confidence intervals for nonparametric inference of the regression function. The theoretical results and appealing finite-sample performance of the suggested two-scale DNN method are illustrated with several simulation examples and a real data application.

Quantifying Methane Influx from Sewer into Wastewater Treatment Processes.

Wastewater treatment contributes substantially to methane (CH4) emissions, yet monitoring and tracing face challenges because the treatment processes are often treated as a "black box". Particularly, despite growing interest, the amount of CH4 carryover and influx from the sewer and its impacts on overall emissions remain unclear. This study quantified CH4 emissions from six wastewater treatment plants (WWTPs) across China, utilizing existing multizonal odor control systems, with a focus on Beijing and Guiyang WWTPs. In the Beijing WWTP, almost 90% of CH4 emissions from the wastewater treatment process were conveyed through sewer pipes, affecting emissions even in the aerobic zone of biological treatment. In the Guiyang WWTP, where most CH4 from the sewer was released at the inlet well, a 24 h online monitoring revealed CH4 fluctuations linked to neighborhood water consumption and a strong correlation to influent COD inputs. CH4 emission factors monitored in six WWTPs range from 1.5 to 13.4 gCH4/kgCODrem, higher than those observed in previous studies using A2O technology. This underscores the importance of considering CH4 influx from sewer systems to avoid underestimation. The odor control system in WWTPs demonstrates its potential as a cost-effective approach for tracing, monitoring, and mitigating CH4.

Molecular insights into linkages among free-floating macrophyte-derived organic matter, the fate of antibiotic residues, and antibiotic resistance genes.

Macrophyte rhizospheric dissolved organic matter (ROM) served as widespread abiotic components in aquatic ecosystems, and its effects on antibiotic residues and antibiotic resistance genes (ARGs) could not be ignored. However, specific influencing mechanisms for ROM on the fate of antibiotic residues and expression of ARGs still remained unclear. Herein, laboratory hydroponic experiments for water lettuce (Pistia stratiotes) were carried out to explore mutual interactions among ROM, sulfamethoxazole (SMX), bacterial community, and ARGs expression. Results showed ROM directly affect SMX concentrations through the binding process, while CO and N-H groups were main binding sites for ROM. Dynamic changes of ROM molecular composition diversified the DOM pool due to microbe-mediated oxidoreduction, with enrichment of heteroatoms (N, S, P) and decreased aromaticity. Microbial community analysis showed SMX pressure significantly stimulated the succession of bacterial structure in both bulk water and rhizospheric biofilms. Furthermore, network analysis further confirmed ROM bio-labile compositions as energy sources and electron shuttles directly influenced microbial structure, thereby facilitating proliferation of antibiotic resistant bacteria (Methylotenera, Sphingobium, Az spirillum) and ARGs (sul1, sul2, intl1). This investigation will provide scientific supports for the control of antibiotic residues and corresponding ARGs in aquatic ecosystems.

Transport and retention of ciprofloxacin with presence of multi-walled carbon nanotubes in the saturated porous media: impacts of ionic strength and cation types.

The environmental fate and risks of ciprofloxacin (CIP) in the subsurface have raised intensive concerns. Herein, the transport behaviors of CIP in both saturated quartz sand and sand/multi-walled carbon nanotubes (MWCNTs) mixtures under different solution ionic strength of the solution and coexisting cation types were investigated. Batch adsorption experiments highlighted growing adsorptive capacity for CIP with the increasing content of MWCNTs in the MWCNTs-quartz sand mixtures (from 0.5% to 1.5%, w/w). Breakthrough curves (BTCs) of CIP in the MWCNTs-quartz sand mixtures were well fitted by the two-site chemical nonequilibrium model (R2 > 0.833). The estimated retardation factors for CIP increased from 9.68 to 282 with growing content of MWCNTs in the sand column, suggesting the presence of MWCNTs significantly inhibited the transport of CIP in saturated porous media. Moreover, the values of retardation factors are negatively correlated with the ionic strength and higher ionic strength could facilitate the transport of CIP in the saturated porous media. Compared with monovalent cations (Na+), the presence of divalent cations (Ca2+) significantly facilitated the transport of CIP in the columns due to the complexation between CIP and Ca2+ as well as deposition of MWCNTs aggregates on the sand surface. Results regarding CIP retention in columns indicated that MWCNTs could enhance the accumulation of CIP in the layers close to the influent of sand columns, while they could hinder upward transport of CIP to the effluent. This study improves our understanding for transport behaviors and environmental risk assessments of CIP in the saturated porous media with MWCNTs.

Intravenous tranexamic acid significantly improved visualization and shortened the operation time in microscopic middle ear surgery: a randomized controlled trial.

BACKGROUND: The microscopic middle ear surgery involves a limited operating space and numerous important anatomical structures in which good visualization is crucial, as even a small amount of bleeding can greatly affect the clarity of surgical field. This study aims to investigate whether intravenous 1 g of tranexamic acid can improve surgical visualization and further shorten the operation time in microscopic middle ear surgery. METHODS: This study is a prospective, randomized, double-blind, controlled trial conducted from December 2021 to December 2022, enrolling patients who were scheduled for microscopic modified radical mastoidectomy due to chronic otitis media. In addition to standard techniques to optimize the surgical field, participants were randomized into the TXA (tranexamic acid) group (1 g diluted to 20 ml normal saline) and the control group (20 ml normal saline). The primary outcome was assessed based on the clarity of the surgical field using the Modena Bleeding Score. Secondary outcomes included operation time, the surgeon satisfaction with the visual clarity, postoperative 24 h coagulation parameters, and the incidence of adverse events. Student's t -test, χ2 test, and ANOVA of repeated measures were used for statistical analyses. RESULTS: A total of 28 patients were enrolled in each group using a 1:1 randomized allocation with similar demographic characteristics, including 24 male and 32 female individuals, and the mean age is 45.6±11.9 years. The surgical visualization in the TXA group was significantly better than that of the control group (2.29±0.46 vs. 2.89±0.31, P <0.001) as assessed by the Modena Bleeding Score. Furthermore, the TXA group demonstrated a shorter operation time compared to the control group (88.61±10.9 vs. 105.2±15.9, P <0.001) and higher surgeon satisfaction with surgical field (7.82±0.55 vs. 6.50±0.64, P <0.001). No statistically significant differences were found in postoperative coagulation parameters in the two groups. No TXA-related adverse events or complications occurred during the 12-month follow-up. CONCLUSION: Intravenous 1 g of TXA can further significantly improve the visual clarity in the microscopic middle ear surgery and shorten the operation time based on other standard measures implemented.

Research Progress and Clinical Value of Subendocardial Viability Ratio.

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, with ischemic heart disease being a major contributor, either through coronary atherosclerotic plaque-related major vascular disease or coronary microvascular dysfunction. Obstruction of coronary blood flow impairs myocardial perfusion, which may lead to acute myocardial infarction in severe cases. The subendocardial viability ratio, also known as the Buckberg index, is a valuable tool for evaluation of myocardial perfusion because it reflects the balance between myocardial oxygen supply and oxygen demand. The subendocardial viability ratio can effectively evaluate the function of the coronary microcirculation and is associated with arterial stiffness. This ratio also has potential value in predicting adverse cardiovascular events and mortality in various populations. Moreover, the subendocardial viability ratio has demonstrated clinical significance in a range of diseases, including hypertension, aortic stenosis, peripheral arterial disease, chronic kidney disease, diabetes, and rheumatoid arthritis. This review summarizes the applications of the subendocardial viability ratio, its particular progress in the relevant research, and its clinical significance in cardiovascular diseases.