Colloidal Phenol-Amine Coating on Implants for Improved Anti-Inflammation and Osteogenesis.

Phenol-amine coatings have attracted significant attention in recent years owing to their adjustable composition and multifaceted biological functionalities. The current preparation of phenol-amine coatings, however, involves a chemical reaction within the solution or interface, resulting in lengthy preparation times and necessitating specific reaction conditions, such as alkaline environments and oxygen presence. The facile, rapid, and eco-friendly preparation of phenol-amine coatings under mild conditions continues to pose a challenge. In this study, we use a macromolecular phenol-amine, Tanfloc, to form a stable colloid under neutral conditions, which was then rapidly adsorbed on the titanium surface by electrostatic action and then spread and fused to form a continuous coating within several minutes. This nonchemical preparation process was rapid, mild, and free of chemical additives. The in vitro and in vivo results showed that the Tanfloc colloid fusion coating inhibited destructive inflammation, promoted osteogenesis, and enhanced osteointegration. These remarkable advantages of the colloidal phenol-amine fusion coating highlight the suitability of its future application in clinical practice.

Disutilities Associated with Intravenous Iron Infusions: Results from a Time Trade-off Survey and Diminishing Marginal Utility Model for Treatment Attributes in China.

Purpose: Treatment process attributes can affect health state utilities associated with therapy. For intravenous iron, used to treat iron deficiency and iron deficiency anemia, research into process attributes is still lacking. This study estimated utilities associated with process attributes for intravenous iron infusions. Methods: An online survey including seven health state vignettes and time trade-off tasks was administered to participants, who were not patients living with iron deficiency or iron deficiency anemia, from a Chinese online panel. Vignettes used an identical description of iron deficiency and iron deficiency anemia but differed in the annual number of infusions, infusion duration, and infusion-associated risk of hypophosphatemic osteomalacia. Disutilities and their rate of change as the number of infusions increased were examined using a power model. Results: The survey was completed by 1091 participants. The highest utilities were observed for one annual infusion of 15-30 minutes or 30-60 minutes, without risk of hypophosphatemic osteomalacia (0.754 and 0.746, respectively). In comparison, more infusions and infusions with a risk of hypophosphatemic osteomalacia were associated with lower utilities. Utility continued to decrease, but at a diminishing rate, as the annual number of infusions increased, with utility decrements of 0.006 and 0.002, respectively, when going from zero to one and from four to five infusions per year. All marginal disutilities were small (values <0.01). Conclusion: This study suggested that treatment attributes of intravenous iron infusions affect health state utilities. Using intravenous iron formulations that allow for fewer and shorter infusions without the risk of hypophosphatemic osteomalacia can reduce the number of visits required and increase patients' quality of life.

Grouting anchor cable active advanced support technology for mining roadways.

Because of the deficiencies in safety and economy of the single hydraulic prop passive advanced support, the grouting anchor cable active advanced support technology is proposed with the Changping Coal Mine 53,081 roadway as the engineering background. By using a combination of theoretical analysis, laboratory tests, numerical simulation, and field tests, the influence of different grouting parameters on the diffusion law of grout is studied. Considering the effect of the stress field on grout migration, a grout seepage-stress coupling model is established. Grouting material ratio tests are carried out and grout parameters are tested. The grouting part of the advanced grouting anchor cable is modeled and solved using the COMSOL Multiphysics numerical software. The results show that the grouting material selected is Portland cement 42.5 and water glass double liquid grout, with a slurry ratio of 15% ACZ-1 type additive and 4% water glass content, and a water-cement ratio of 0.6. The grouting pressure for the 53,081 roadway grouting anchor cable advanced support is 5 MPa, the grouting time is 6 min, and the grouting anchor cable spacing is 2000 mm × 1000 mm. The engineering application shows that the maximum roof subsidence is 180 mm, the maximum separation value at a depth of 9 m is 24 mm, and the maximum separation value at a depth of 3 m is 90 mm. The research results have achieved effective advanced support for the 53,081 roadway, replacing the single hydraulic prop, and provided a theoretical basis for the subsequent design of advanced support parameters for mining roadways.

Myocardial-Targeting Tannic Cerium Nanocatalyst Attenuates Ischemia/Reperfusion Injury.

Ischemic heart disease (IHD) is one of the leading causes of death worldwide. Medications or surgery have been considered as effective protocols to treat IHD for decades. Yet the reperfusion of the blood flow frequently leads to the generation of excessive reactive oxygen species (ROS), causing prominent and irreversible damage to the cardiomyocytes. In the present work, tannic acid-assembled tetravalent cerium (TA-Ce) nanocatalysts with appealing cardiomyocyte-targeting and antioxidation capability have been synthesized and applied for the effective and biocompatible ischemia/reperfusion injury therapeutics. TA-Ce nanocatalysts could effectively rescue the cardiomyocytes from oxidative stress induced by H2 O2 challenge as well as oxygen-glucose deprivation in vitro. In the murine ischemia/reperfusion model, cardiac accumulation and intracellular ROS scavenging could be achieved against the pathology, substantially reducing the myocardial infarct area and recovering heart functionality. This work illuminates the design of nanocatalytic metal complexes and their therapeutic prospects in ischemic heart diseases with high effectiveness and biocompatibility, paving the way for the clinical translation from bench to bedside.

Efficacy of diet restriction with or without probiotic for treatment of patients with IBS-D: Phase I-II clinical trial.

BACKGROUND AND AIM: Diet is a major contributor to irritable bowel syndrome (IBS) and is also a powerful tool for treatment of IBS. This study compared two diets and explored the effectiveness of the diets when combined with a probiotic for treatment of IBS-D patients. METHODS: Phase I, patients were randomized into groups; control, cold/spicy/fried restricted diet (CSF res diet), IgG positive restricted diet (IgG res diet), and a combination both diets (CSF + IgG res diet). Phase II, patients were randomized into IgG res diet + placebo and IgG res diet + probiotic. Both interventions were 12 weeks in duration. Symptom Severity Scale (IBS-D-SSS) and IgG titer were assessed at the beginning and the end of the study. RESULTS: Totals of 214 and 167 patients completed the two parts of the study, respectively. After intervention, IBS-D-SSS and TIgG grade were significantly improved compared to baseline, with results similar to the control group. In general, there were decreases in IBS-D-SSS and TIgG grade that were significantly different among the groups. There were exceptions; no differences were observed for IBS-D-SSS between the IgG res diet and CSF + IgG res diet, or TIgG grade between the CSF res diet, IgG res diet, and CSF + IgG res diet. However, the CSF res diet and IgG res diet had a synergistic effect that decreased IBS-D-SSS and TIgG titer, with a greater contribution by the IgG res diet. Therefore, we evaluated the IgG res diet with either placebo or probiotic and found that IBS-D-SSS and TIgG grade decreased from baseline. There was a significant decrease in IBS-D-SSS with the probiotic but TIgG grade was not significantly different between the IgG diet + placebo and IgG diet + probiotic diet. CONCLUSIONS: Both the CSF res diet and IgG res diet improved IBS symptoms and demonstrated synergy, although the IgG res diet had a greater contribution. Further, when intolerant foods cannot be eliminated from a diet, avoiding uncooked, cold, spicy, fried, and alcoholic foods is a superior choice. The IgG res diet combined with Bifidobacteria was the best dietary choice and may function though a non-IgG pathway.

The Relationship Between Major Food Sources of Fructose and Cardiovascular Outcomes: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

There is emerging evidence of associations between intake of sugar-sweetened beverages (SSBs), those that include various forms of added sugar, and increased risk of cardiovascular disease (CVD) but whether consumption of other dietary sources of fructose affects CVD is unclear. In this study, we conducted a meta-analysis to examine potential dose-response relationships between such foods and CVD, coronary heart disease (CHD), and stroke morbidity and mortality. We systematically searched the literature indexed in PubMed, Embase, and the Cochrane Library from the inception of each database to February 10, 2022. We included prospective cohort studies analyzing the association between at least 1 dietary source of fructose and CVD, CHD, and stroke. Based on data from 64 included studies, summary HRs and 95% CIs were calculated for the highest intake category compared with the lowest, and dose-response analyses were performed. Of all fructose sources examined, only SSB intakes showed positive associations with CVD, giving summary HRs per 250 mL/d increase of 1.10 (95% CI: 1.02, 1.17) for CVD, 1.11 (95% CI: 1.05, 1.17) for CHD, 1.08 (95% CI: 1.02, 1.13) for stroke morbidity, and 1.06 (95% CI: 1.02, 1.10) for CVD mortality. Conversely, 3 dietary sources showed protective associations: between fruits and CVD morbidity (HR: 0.97; 95% CI: 0.96, 0.98), fruits and CVD mortality (HR: 0.94; 95% CI: 0.92, 0.97), yogurt and CVD mortality (HR: 0.96; 95% CI: 0.93, 0.99), and breakfast cereals and CVD mortality (HR: 0.80; 95% CI: 0.70, 0.90). All these relationships were linear except for fruit, which was J-shaped: CVD morbidity was the lowest at 200 g/d and there was no protective association above 400 g/d. These findings indicate that the adverse associations between SSBs and CVD, CHD, and stroke morbidity and mortality do not extend to other dietary sources of fructose. The food matrix seemed to modify the association between fructose and cardiovascular outcomes.

Occurrence and distribution of microplastics in coastal plain soils under three land-use types.

Microplastic pollution is an issue of major environmental concern worldwide. Land-use type may affect the abundance, polymer types, and distribution characteristics of soil microplastics but their distribution remains unknown on the coastal plain of east China. Here, the abundance of microplastics in farmland (FL), plantation (P), and orchard/secondary forest (OSF) soils was determined on the east China coastal plain, and characteristics of the microplastics (shape, size, colour, and polymer composition) were analysed in soil samples collected from 33 sites. The average abundances of microplastics in FL, P, and OSF soils on the coastal plain of the east China coast were 185, 109, and 150 items kg-1, respectively. Small particles, fibres and transparent particles were the main characteristics of the microplastics observed. The polymer types were mainly PP and PET. The abundance of microplastics in farmland was positively correlated with population density in the study area. Therefore, agricultural activities associated with high population density are the main factors leading to the high abundance of microplastics in farmland soil.

Fabry disease: Mechanism and therapeutics strategies.

Fabry disease is a monogenic disease characterized by a deficiency or loss of the α-galactosidase A (GLA). The resulting impairment in lysosomal GLA enzymatic activity leads to the pathogenic accumulation of enzymatic substrate and, consequently, the progressive appearance of clinical symptoms in target organs, including the heart, kidney, and brain. However, the mechanisms involved in Fabry disease-mediated organ damage are largely ambiguous and poorly understood, which hinders the development of therapeutic strategies for the treatment of this disorder. Although currently available clinical approaches have shown some efficiency in the treatment of Fabry disease, they all exhibit limitations that need to be overcome. In this review, we first introduce current mechanistic knowledge of Fabry disease and discuss potential therapeutic strategies for its treatment. We then systemically summarize and discuss advances in research on therapeutic approaches, including enzyme replacement therapy (ERT), gene therapy, and chaperone therapy, as well as strategies targeting subcellular compartments, such as lysosomes, the endoplasmic reticulum, and the nucleus. Finally, the future development of potential therapeutic strategies is discussed based on the results of mechanistic studies and the limitations associated with these therapeutic approaches.

Intrathecal hydromorphone for analgesia after partial hepatectomy: a randomized controlled trial.

INTRODUCTION: There is substantial interest in adding intrathecal opioids, such as hydromorphone to the multimodal pain management strategies. We conducted a randomized controlled trial to examine whether adding intrathecal hydromorphone to a multimodal strategy could safely improve analgesic efficacy for patients undergoing partial hepatectomy. METHODS: A total of 126 adult patients undergoing partial hepatectomy under general anesthesia were randomly assigned to receive intrathecal hydromorphone (100 µg) or no block. The primary outcome was the incidence of moderate to severe pain during movement at 24 hours after surgery. Secondary outcomes included the incidence of moderate to severe pain during rest or movement at different times within 72 hours, pain scores during rest or movement within 72 hours after surgery, analgesic use, adverse events, and indicators of postoperative recovery. RESULTS: Among the 124 patients analyzed, the intrathecal hydromorphone group showed a lower incidence of moderate to severe pain during movement at 24 hours after surgery (29.0% vs 50%; RR 0.58, 95% CI 0.37 to 0.92) than the control group. However, the absolute difference in pain scores on a numerical rating scale was less than 1 between the two groups at 24 hours after surgery. Mild pruritus within the first 24 hours after surgery was more frequent in the intrathecal hydromorphone group (19.4% vs 4.8%; p=0.01). DISCUSSION: Intrathecal hydromorphone 100 µg reduced the incidence of moderate to severe pain and pain scores during movement within 24 hours after partial hepatectomy. However, the difference in pain scores may not be clinically significant, and intrathecal hydromorphone 100 µg did not significantly improve other analgesic or functional outcomes. Further investigation is needed to optimize the intrathecal hydromorphone dose. TRIAL REGISTRATION NUMBER: ChiCTR2000030652.

Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability.

The prevalent use of electronic cigarettes (e-cigarettes) has increased exponentially in recent years, especially in youth who are attracted to flavored e-cigarettes. Indeed, e-cigarette or vaping product use-associated lung injury (EVALI) cases started to emerge in the United States in August 2019, resulting in 2807 hospitalized cases and 68 deaths as of 18 February 2020. In the present study, we investigated, for the first time, whether flavored and nicotine containing e-cigarettes induce endothelial dysfunction to result in impaired angiogenesis and wound healing particularly under diabetic condition. Nicotine containing e-cigarettes with various contents of nicotine (0, 1.2%, 2.4%), and flavored e-cigarettes of classic tobacco, mint, menthol, and vanilla or fruit from BLU (nicotine 2.4%) or JUUL (nicotine 3%), were used to treat endothelial cells in vitro and streptozotocin-induced diabetic mice in vivo. Endothelial cell superoxide production, determined by dihydroethidium (DHE) fluorescent imaging and electron spin resonance (ESR), was markedly increased by exposure to e-cigarette extract (e-CSE) in a nicotine-content dependent manner, while nitric oxide (NO) bioavailability detected by DAF-FM fluorescent imaging was substantially decreased. All of the different flavored e-cigarettes examined also showed significant effects in increasing superoxide production while diminishing NO bioavailability. Endothelial cell apoptosis evaluated by caspase 3 activity was markedly increased by exposure to e-CSE prepared from flavored and nicotine containing e-cigarettes. Endothelial monolayer wound assays revealed that nicotine-containing and flavored e-cigarettes induced impaired angiogenic wound repair of endothelial cell monolayers. Furthermore, vascular endothelial growth factor (VEGF) stimulated wound healing in diabetic mice was impaired by exposure to e-CSEs prepared from nicotine-containing and flavored e-cigarettes. Taken together, our data demonstrate for the first time that flavored and nicotine-containing e-cigarettes induce endothelial dysfunction through excessive ROS production, resulting in decreased NO bioavailability, increased endothelial cell apoptosis, and impairment in angiogenesis and wound healing, especially under diabetic condition. These responses of endothelial dysfunction likely underlie harmful effects of e-cigarettes in endothelial-rich organs, such as heart and lungs. These data also indicate that rigorous regulation on e-cigarette use should be enforced in diabetic and/or surgical patients to avoid severe consequences from impaired angiogenesis/wound healing.

Surgeon-performed fine-needle aspiration for lymph nodes behind the big cervical vessels in papillary thyroid cancer.

Objective: This study aimed to describe the technique of surgeon-performed ultrasound (US)-guided fine-needle aspiration (FNA) of cervical retrovascular lymph nodes in papillary thyroid cancer (PTC) patients and analyze its efficacy. Methods: This study included consecutive patients with retrovascular suspicious lymph nodes who had FNA performed by surgeons. The technique and efficacy of four different puncture routes were assessed. Results: A total of 102 lymph node FNAs were performed on 100 patients. None yield insufficient aspiration, while 2% of FNA cytology result in an indeterminate diagnosis. No severe complication was observed. Cytologic testing plus thyroglobulin washout indicated sensitivity, specificity, positive predictive value, and negative predictive value in diagnosing nodal metastasis were 99%, 93%, 97%, and 97%, respectively. There was no significant difference in the test accuracy of FNA through different routes. Conclusions: In PTC patients, suspicious lymph nodes behind the big cervical vessels should not be considered a contraindication to FNA. They can be diagnosed safely and accurately using appropriate puncture routes.Level of evidence: 4.

Intravenous iron for the treatment of iron deficiency anemia in China: a patient-level simulation model and cost-utility analysis comparing ferric derisomaltose with iron sucrose.

OBJECTIVES: Two intravenous (IV) iron formulations, ferric derisomaltose (FDI) and iron sucrose (IS), are currently available for the treatment of iron deficiency anemia (IDA) in China. Clinical studies have demonstrated that FDI has an improved efficacy and safety profile versus IS, while requiring fewer infusions to correct iron deficits. Based on these findings, the present study evaluated the costs and benefits of FDI and IS for the treatment of IDA, from a healthcare system and societal perspective in China. METHODS: A patient-level model was developed to project time to hematological response and incidence of cardiovascular adverse events and hypersensitivity reactions (HSRs) associated with FDI and IS over 5 years. Costs included iron acquisition, administration, and adverse event/HSR treatment costs, based on published studies, fee schedules, and a physician survey. Health state utilities associated with adverse events, HSRs, and the number of infusions were obtained from the literature and a time trade-off survey. RESULTS: From a healthcare system perspective, FDI was associated with incremental costs of RMB 1,934 (purchasing power parity USD 462) and incremental quality-adjusted life expectancy of 0.078 quality-adjusted life-years (QALYs) versus IS, yielding an incremental cost-utility ratio of RMB 24,901 (USD 5,949) in the base case scenario. From a societal perspective, FDI was associated with reduced total costs and therefore dominant versus IS. LIMITATIONS: Limitations included the absence of clinical data specific to China and insufficient data to model persistence with treatment. CONCLUSIONS: This was the first cost-utility analysis comparing FDI and IS for the treatment of IDA in China. Based on a patient-level model, FDI was found to improve quality of life and reduce administration and adverse events costs relative to IS. Using the 2020 Chinese gross domestic product per capita of RMB 72,447 (USD 17,307) as a cost-effectiveness threshold, FDI would be considered cost-effective in China.

Ferric derisomaltose (FDI) was approved in February 2021 for the treatment of iron deficiency anemia (IDA) in China and allows for fast iron correction in one visit with a good safety profile. The current standard of care in China is iron sucrose (IS). Clinical and economic decision-making can benefit from having longer-term projections on the benefits and costs of new medications relative to the current standard of care, which is why we conducted the first cost-utility analysis of FDI and IS for China. We developed a patient-level model that captured the effects of the iron formulations on IDA, in addition to incidences of adverse events and hypersensitivity reactions (HSRs) associated with either formulation. Costs of the iron formulations, their administration, and of treatments for adverse events and HSR were modeled alongside the quality of life effects of IDA, adverse events, HSRs, and iron infusions. We used published clinical data and Chinese cost data to inform our model. Our results show that FDI was associated with higher quality-adjusted life expectancy than IS, regardless of the perspective of the analysis, and higher total costs from the healthcare system perspective. From a societal perspective, FDI was associated with lower costs due to reduced travel and waiting time and smaller productivity losses given there were fewer appointments. These results imply that FDI is likely good value for money for the healthcare system and indeed cost-saving for society relative to IS, which has so far been the most widely used IV iron treatment in China.

Effect of Polyaniline and Graphene Oxide Modified Carbon Felt on Adsorption and Immobilization of Acidithiobacillus ferrooxidans.

Biological desulfurization plays an increasingly important role in desulfurization industry. A strain of Acidithiobacillus ferrooxidans ZJ-2 with high Fe2+ oxidizing efficiency was in this study isolated and screened to remove hydrogen sulfide from biogas. To further improve its oxidation efficiency, A. ferrooxidans ZJ-2 was immobilized using carbon felt (CF), modified with graphene oxide (GO) and polyaniline (PANI), as immobilized carrier. The effects of immobilization on strain's Fe2+ oxidation efficiency and impact of PANI and GO on CF were also investigated. Raman spectra and atomic force microscopy showed that CF was successfully modified using GO and PANI. Cyclic voltammetry and electrochemical impedance spectroscopy measurements revealed that the electrochemical properties of modified CF were improved, presenting the following trend in conductivity: CF< GO-modified CF (GO-CF) < PANI-modified CF (PANI-CF) < PANI/GO-modified CF (PANI/GO-CF). The resistance of modified CF was lower than that of unmodified CF, and exhibited the following trend: CF > GO-CF > PANI-CF > GO/PANI-CF. While PANI-CF inhibited growth of free and immobilized A. ferrooxidans ZJ-2, GO-CF was conducive to microbial growth and increased cell density and oxidation ability of A. ferrooxidans ZJ-2. Thus, the present study developed an immobilized bacterial carrier that had better conductivity and lower resistance and was efficient in immobilizing A. ferrooxidans and could be used for biogas desulfurization in biological and biochemical combined reactors.

Nanozymes-recent development and biomedical applications.

Nanozyme is a series of nanomaterials with enzyme-mimetic activities that can proceed with the catalytic reactions of natural enzymes. In the field of biomedicine, nanozymes are capturing tremendous attention due to their high stability and low cost. Enzyme-mimetic activities of nanozymes can be regulated by multiple factors, such as the chemical state of metal ion, pH, hydrogen peroxide (H2O2), and glutathione (GSH) level, presenting great promise for biomedical applications. Over the past decade, multi-functional nanozymes have been developed for various biomedical applications. To promote the understandings of nanozymes and the development of novel and multifunctional nanozymes, we herein provide a comprehensive review of the nanozymes and their applications in the biomedical field. Nanozymes with versatile enzyme-like properties are briefly overviewed, and their mechanism and application are discussed to provide understandings for future research. Finally, underlying challenges and prospects of nanozymes in the biomedical frontier are discussed in this review.

Mitochondrial protein hyperacetylation underpins heart failure with preserved ejection fraction in mice.

Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction (HFrEF). The prevalence of HFpEF continues to increase, while the pathogenic mechanisms underlying HFpEF remain largely elusive and evidence-based therapies are still lacking. This study was designed to investigate the metabolic signature of HFpEF and test the potential therapeutic intervention in a mouse model. By utilizing a "3-Hit" HFpEF mouse model, we observed a global protein hyperacetylation in the HFpEF hearts as compared to the pressure overload-induced HFrEF and adult/aged non-heart failure (NHF) hearts. Acetylome analysis identified that a large proportion of the hyperacetylated proteins (74%) specific to the HFpEF hearts are in mitochondria, and enriched in tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and fatty acid oxidation. Further study showed that the elevated protein acetylation in the HFpEF hearts was correlated with reduced NAD+/NADH ratio, impaired mitochondrial function, and depleted TCA cycle metabolites. Normalization of NAD+/NADH ratio by supplementation of nicotinamide riboside (NR) for 30 days downregulated the acetylation level, improved mitochondrial function and ameliorated HFpEF phenotypes. Therefore, our study identified a distinct protein acetylation pattern in the HFpEF hearts, and proposed NR as a promising agent in lowering acetylation and mitigating HFpEF phenotypes in mice.

Preoperative serum alpha-hydroxybutyrate dehydrogenase level as a predictor of postoperative mortality and morbidity after noncardiac surgery: A propensity-adjusted analysis.

BACKGROUND: Preoperative serum alpha-hydroxybutyrate dehydrogenase is reportedly associated with myocardial infarction. Myocardial injury after noncardiac surgery is independently associated with postoperative mortality. However, the association between preoperative alpha-hydroxybutyrate dehydrogenase and outcomes after noncardiac surgery has not been researched. We aimed to assess the association between preoperative serum alpha-hydroxybutyrate dehydrogenase levels and mortality and morbidity after noncardiac surgery. METHODS: We conducted a retrospective cohort study on patients undergoing noncardiac surgery from 2018 to 2020 in Sichuan University West China Hospital. After multivariate adjustment, the alpha-hydroxybutyrate dehydrogenase level was verified to be associated with postoperative outcomes by logistic regression analyses and propensity score weighting methods. RESULTS: We obtained data from 130,880 patients. An elevated preoperative serum alpha-hydroxybutyrate dehydrogenase level was associated with increasing mortality (odds ratio 1.244, 1.190-1.300; P < .001), myocardial injury after noncardiac surgery (odds ratio 1.198, 1.141-1.257; P < .001), and intensive care unit admission (odds ratio 1.138, 1.111-1.166; P < .001) in logistic regression analyses. The covariate balancing generalized propensity score methodology demonstrated similar results. After classifying alpha-hydroxybutyrate dehydrogenase as a binary variable with a cut-off value of 182, we found that mortality, myocardial injury after noncardiac surgery, and intensive care unit admission >24 hours were significantly higher in the elevated alpha-hydroxybutyrate dehydrogenase group (5.458% vs 0.737%; odds ratio 1.771, 1.533-2.046; P < .001), (3.598% vs 0.572%; odds ratio 1.636, 1.393-1.922; P < .001), and (18.182% vs 6.442%; odds ratio 1.430, 1.327-1.542; P < .001), respectively. Similarly, the inverse-probability-of-treatment weighted estimation demonstrated similar results. CONCLUSION: Our results suggest that the preoperative serum alpha-hydroxybutyrate dehydrogenase level was associated with in-hospital mortality, myocardial injury after noncardiac surgery, and intensive care unit admission after noncardiac surgery.

Multigenerational exposure of the collembolan Folsomia candida to soil metals: Adaption to metal stress in soils polluted over the long term.

Multigenerational tests provide a comprehensive assessment of the long-term toxicity of pollutants. Here, the multigenerational effects of soil metal contamination on Folsomia candida were investigated over five generations (generations 1-5: F1-F5). Nine soils with varying physicochemical properties and degrees of metal pollution were studied. The selected endpoints were survival, reproduction, body size and body metal concentrations. F. candida was cultured only up to the fifth generation with high reproduction in contaminated acid soils where reproduction was at least 5 times that in neutral soils and 20 times that in calcareous soils. Correlation analysis indicated that soil pH (68.9% contribution) and cation exchange capacity (CEC, 15.4% contribution) were more important factors than pollution level affecting the reproduction of F. candida. No significant difference was observed in adult survival or adult length over five generations. The highest collembolan body Cd concentrations in soils A1-A3 were 3.15, 2.93 and 3.23 times those in F1, with similar results for body Pb. A similar trend in reproduction and juvenile length was observed with an initial decrease (p < 0.05) and then an increase (p < 0.05) over the generations in each acid soil; the opposite trend occurred in the changes in body cadmium (Cd) and lead (Pb) concentrations which increased initially (p < 0.05) and then decreased (p < 0.05) compared to the original concentrations of the first generation. The results indicate that F. candida can adapt to soil metal stress during multigenerational exposure and the adaption energy may be related to a tradeoff between reproduction or growth of juveniles and the detoxification of metals accumulated in the body. Soil properties, especially pH and CEC, had a substantial influence on the long-term survival of the collembolan in the metal-polluted soils.

Indications of Superselective Neck Dissection in Patients With Lateral Node Metastasis of Papillary Thyroid Carcinoma.

OBJECTIVE: The extent of neck dissection in papillary thyroid carcinoma (PTC) patients with lateral neck metastasis is controversial. This work aims to screen the patients suitable for superselective neck dissections including only levels III-IV. STUDY DESIGN: Prospective observational cohort study. SETTING: The study was conducted in a high-volume tertiary care setting. METHODS: A total of 134 consecutive previously untreated PTC patients with lateral neck metastases and subjected to 154 therapeutic lateral neck dissections (including levels II, III, IV, and VB) between June 2018 and March 2021 were enrolled. Fine-needle aspiration was performed preoperatively at each suspicious neck level. Clinical predictors were analyzed for occult lymph node metastases at levels II and VB. RESULTS: As a result, 44.8% and 5.8% of neck specimens exhibited metastatic lymph nodes at levels II and VB. In addition, univariate and multivariate analyses showed that the primary tumor in the ipsilateral thyroid upper lobe (P = .016, odds ratio = 3.528) and clinically multiple metastatic lymph nodes in level III-IV (P = .005, odds ratio = 6.414) were independent predictive factors for occult level II metastases. All 3 (1.9%) occult metastases at level VB were found in necks with preoperative multiple lymph node metastases. CONCLUSIONS: A superselective lateral neck dissection including levels III to IV may be considered in patients with PTC when the preoperative evaluation identifies a single lymph node metastasis located at levels III to IV and the primary tumor is not in the upper lobe of the ipsilateral thyroid.

An SNP at the target site of cid-miR-nov-1043 in the TOLLIP 3' UTR decreases mortality rate in grass carp subjected to ENU-induced mutagenesis following grass carp reovirus infection.

N-ethyl-N-nitrosourea (ENU) selection is a useful technique to generate new mutations that may cause some functional changes in the gene. Through our previous genomic bulked segregant analysis (BSA), one single nucleotide polymorphism (SNP) at the 3' UTR of Toll interacting protein gene (TOLLIP982T>C) was identified in grass carp (Ctenopharyngodon idella) subjected to ENU-induced mutagenesis. We found that the overexpression of cid-miR-nov-1043 mimics significantly suppressed the luciferase activity of the TOLLIP 3' UTR, but TOLLIP982T>C mutation at the target site can decrease the binding affinity between the miRNA cid-miR-nov-1043 and TOLLIP 3' UTR, reducing the inhibition of TOLLIP mRNA transcription in grass carp subjected to ENU-induced mutagenesis. More importantly, we demonstrated that TOLLIP mRNA transcription levels in the gills, liver, kidney and the isolate white cells of the mutant grass carp were significantly (p < 0.01) higher than those in the corresponding tissues from the wild-type grass carp following infection with Grass Carp Reovirus (GCRV) for seven days, while the downstream gene of TOLLIP transforming growth factor ß-activated kinase 1 (TAK1) and TAK1-binding protein 1 (TAB1), were higher expressed in wild-type grass carp. As a negative regulator in the pro-inflammatory pathway of NF-κB, TOLLIP inhibits the excessive inflammation in ENU grass carp after GCRV infection. Consistent with the TOLLIP expression, histopathological results demonstrated more severe inflammation in wild-type grass carp, compared to the TOLLIP982T>C mutant grass carp on the seventh day. Severe inflammation will lead to thoroughly infiltration of chloride and inflammatory cells in the gill filaments. This seriously hindered the exchange of oxygen, which ultimately disrupted blood circulation. Meanwhile, the survival rate of the mutant grass carp was significantly (p < 0.01) higher than that of the wild-type grass carp, indicating that the TOLLIP982T>C mutants showed strong anti-viral abilities. Our results revealed that an SNP in the TOLLIP 3' UTR may contribute to the suppression of serve inflammation subjected to ENU-induced mutagenesis following GCRV infection, which may be helpful for future resistant breeding development of grass carp.