Adverse event profiles of drug-induced liver injury caused by antidepressant drugs: a disproportionality analysis.

Background: Antidepressants are widely used to manage depression and other psychiatric diseases. A previous study revealed that hepatotoxicity was the main adverse event related to antidepressants. Therefore, drug-induced liver injury (DILI) caused by antidepressants deserves more attention. Objectives: To investigate DILI adverse events reported due to antidepressant use in the United States Food and Drug Administration Adverse Events Reporting System (FAERS) database. Research design: A disproportionality analysis of spontaneously reported adverse events was conducted to assess the association between antidepressant drugs and DILI. Methods: FAERS data from 1 January 2004 to 31 December 2021 were compiled and analyzed using the reporting odds ratio (ROR) and information component (IC). Results: As per the FAERS database, of the 324,588 cases that were administered antidepressants, 10,355 were identified as cases with DILI. Among the identified 42 antidepressants, nefazodone (n = 47, ROR = 7.79, IC = 2.91), fluvoxamine (n = 29, ROR = 4.69, IC = 2.20), and clomipramine (n = 24, ROR = 3.97, IC = 1.96) had the highest ROR for cholestatic injury; mianserin (n = 3, ROR = 21.46, IC = 3.99), nefazodone (n = 264, ROR = 18.67, IC = 3.84), and maprotiline (n = 15, ROR = 5.65, IC = 2.39) for hepatocellular injury; and nefazodone (n = 187, ROR = 12.71, IC = 0.48), clomipramine (n = 35, ROR = 2.07, IC = 0.26), and mirtazapine (n = 483, ROR = 1.96, IC = 0.94) for severe drug-related hepatic disorders. Only nefazodone elicited hepatic failure signals (n = 48, ROR = 18.64, IC = 4.16). There are limited reports on the adverse reactions of relatively new antidepressant drugs, such as milnacipran, viloxazine, esketamine, and tianeptine, and those not approved by the Food and Drugs Administration, such as reboxetine and agomelatine. Conclusion: A significant association was observed between DILI and nefazodone. Duloxetine and clomipramine were associated with three DILI categories, except hepatic failure. The disproportionality analysis cannot conclude on a definite causal link between antidepressants and DILI. Additional research is required to assess new-generation antidepressants for their propensity to cause DILI.

Adverse events reported on drug-induced liver injury caused by antidepressants Introduction: Adverse drug events (ADEs) refer to all harmful events related to medications, including adverse drug reactions (ADRs) and other unexpected events. ADEs encompass a wider range and are very important for the post-market surveillance of drugs. This study investigated the voluntary reporting of drug-induced liver injury (DILI) adverse events associated with antidepressant drugs. Methods: We retrieved data on DILI and related terms submitted between 2004 and 2021 from the United States Food and Drug Administration Adverse Events Reporting System (FAERS) database. We analyzed the data for the detection of DILI signals associated with antidepressants. Results: We retrieved and analyzed 324,588 reports on antidepressant drugs. A total of 10,355 reports were associated with DILI. The three drugs with the highest reporting odds ratio (ROR) in each DILI category were as follows: cholestatic injury (nefazodone, fluvoxamine, and clomipramine)hepatocellular injury (mianserin, nefazodone, and maprotiline)hepatic failure (nefazodone)drug related hepatic disorders-severe events (nefazodone, clomipramine, and mirtazapine) The absence of signals from some drugs may be due to: non-association with DILInovelty of the drug in the marketnon-approval from the Food and Drugs Administration (FDA)lack of voluntary reporting of adverse events due to other reasons Conclusion: Drug safety studies utilizing publicly available large databases allowed the evaluation of the safety profile of widely used antidepressant drugs in clinical practice. Nefazodone, duloxetine, and clomipramine were associated with significant DILI signals. Further research is needed to determine the safety concerns of new-generation antidepressants.

Enhancing CO2 Electroreduction to C2 Products on Metal-Nitrogen Sites by Regulating H2O Dissociation.

Water dissociation remarkably affects the CO2 reduction to CO and HCOOH, but whether it is effective for two-carbon product formation on M-Nx-containing catalysts is still ambiguous. Herein, by using a fluorinated metal phthalocyanine (MPc-F) as the M-N4-based model electrocatalyst, experimental and theoretical results reveal that the H2O-dissociation-induced active H species decrease the overpotential of the *CO hydrogenation to *CHO and facilitate the C-C coupling between *CHO and neighboring CO. Such an effect is strengthened by an increase in the *CO binding strength on the metal center. By introducing CuPc as the H2O dissociation catalyst into MPc-F (MPc-F/CuPc) to accurately regulate the H2O dissociation, the faradic efficiency of C2 products on FePc-F/CuPc and MnPc-F/CuPc increases from 0% (FePc-F and MnPc-F) to 26 and 36%, respectively. This work develops a novel strategy for enhancing the selectivity of M-Nx-containing catalysts to C2 products and reveals the correlation between H2O dissociation and C2 product formation.

Analysis of the spatiotemporal evolution and influencing factors of green development level in the manufacturing industry.

The manufacturing sector is the main battlefield of energy saving and carbon reduction in China, and vigorously promoting energy saving and carbon reduction in manufacturing and enhancing the green development level are the key links to support China's realization of the dual-carbon goal. The article adopts the SBM-GML model to measure the level of green development of the manufacturing industry in China. Based on this, it analyzes the spatio-temporal characteristics and the evolution law of the level of green development of the manufacturing industry by using the Dagum Gini Coefficient and Kernel Density Estimation. Using a spatial econometric model to explore the influencing factors of the level of green development of the manufacturing industry. The study finds that the green development level of the manufacturing industry has achieved remarkable results in recent years, but there are differences in the development level of each region. The regional differences in the level of green development of the manufacturing industry are significant. The optimization of manufacturing structure is a key factor influencing the level of green development of the manufacturing industry, and there is a positive spatial spillover effect of manufacturing structure optimization. However, The green development of the manufacturing industry shows a negative spatial spillover effect. The article proposes optimization paths based on the requirements of dual-carbon targets and regional characteristics, which is an important inspiration and reference for the green development level of the manufacturing industry in the world.

Oxidation of chromium(â ¢): A potential risk of using chemical oxidation processes for the remediation of 2-chlorophenol contaminated soils.

Chemical oxidation processes are widely used for the remediation of organically contaminated soils, but their potential impact on variable-valence and toxic metals such as chromium (Cr) is often overlooked. In this study, we investigated the risk of Cr(Ⅲ) oxidation in soils during the remediation of 2-chlorophenol (2-CP) contaminated soils using four different processes: Potassium permanganate (KMnO4), Modified Fenton (Fe2+/H2O2), Alkali-activated persulfate (S2O82-/OH-), and Fe2+-activated persulfate (S2O82-/Fe2+). Our results indicated that the KMnO4, Fe2+/H2O2, and S2O82-/Fe2+ processes progressively oxidized Cr(III) to Cr(Ⅵ) during the 2-CP degradation. The KMnO4 process likely involved direct electron transfer, while the Fe2+/H2O2 and S2O82-/Fe2+ processes primarily relied on HO• and/or SO4•- for the Cr(III) oxidation. Notably, after 4 h of 2-CP degradation, the Cr(VI) content in the KMnO4 process surpassed China's 3.0 mg kg-1 risk screening threshold for Class I construction sites, and further exceeded the 5.7 mg kg-1 limit for Class II construction sites after 8 h. Conversely, the S2O82-/OH- process exhibited negligible oxidation of Cr(III), maintaining a low oxidation ratio of 0.13%, as highly alkaline conditions induced Cr(III) precipitation, reducing its exposure to free radicals. Cr(III) oxidation ratio was directly proportional to oxidant dosage, whereas the Fe2+/H2O2 process showed a different trend, influenced by the concentration of reductants. This study provides insights into the selection and optimization of chemical oxidation processes for soil remediation, emphasizing the imperative for thorough risk evaluation of Cr(III) oxidation before their application.

Umbilical Cord Blood and UC-MSCs Combined with Low-Dose Immunosuppressant in the Treatment of Elderly Patients with Pure Red Cell Aplastic: A Case Series.

INTRODUCTION: At present, cyclosporine (CsA) is the first-line treatment for Pure Red Cell Aplasia (PRCA), but CsA administration can be associated with a number of side effects due to its high toxicity. Therefore, it is urgent to explore a safe and effective treatment for elderly patients who cannot be treated with conventional doses of CsA, especially those with multiple complications. Allogeneic Stem Cell Transplantation (ASCT) for PRCA is a promising treatment, but reports of using umbilical cord blood (UCB) are very rare. CASE PRESENTATION: In this report, UCB and umbilical cord mesenchymal stem cells (UC-MSCs) combined with low-dose CsA (1-3mg/kg/d) were used to treat 3 elderly patients who were diagnosed with PRCA combined with multiple complications in heart, lung, and renal. The treatments were successful without complications, and 12 months after stem cell infusion, the blood tests of the patients came normal. Moreover, the function of the liver, heart, and kidney continued to be stable. CONCLUSION: This report provides an effective regimen of using UCB and UC-MSCs combined with low-dose CsA (1-3 mg/kg/d) to treat PRCA, especially for elderly patients with multiple complications who cannot use the conventional dosage.

Exogenous Glucose Interferes with Antimicrobial-Mediated ROS Accumulation and Bacterial Death.

Glucose is widely used in the reconstitution of intravenous medications, which often include antimicrobials. How glucose affects antimicrobial activity has not been comprehensively studied. The present work reports that glucose added to bacteria growing in a rich medium suppresses the bactericidal but not the bacteriostatic activity of several antimicrobial classes, thereby revealing a phenomenon called glucose-mediated antimicrobial tolerance. Glucose, at concentrations corresponding to blood-sugar levels of humans, increased survival of Escherichia coli treated with quinolones, aminoglycosides, and cephalosporins with little effect on minimal inhibitory concentration. Glucose suppressed a ROS surge stimulated by ciprofloxacin. Genes involved in phosphorylated fructose metabolism contributed to glucose-mediated tolerance, since a pfkA deficiency, which blocks the formation of fructose-1,6-bisphosphate, eliminated protection by glucose. Disrupting the pentose phosphate pathway or the TCA cycle failed to alter glucose-mediated tolerance, consistent with an upstream involvement of phosphorylated fructose. Exogenous sodium pyruvate or sodium citrate reversed glucose-mediated antimicrobial tolerance. Both metabolites bypass the effects of fructose-1,6-bisphosphate, a compound known to scavenge hydroxyl radical and chelate iron, activities that suppress ROS accumulation. Treatment with these two compounds constitutes a novel way to mitigate the glucose-mediated antimicrobial tolerance that may exist during intravenous antimicrobial therapy, especially for diabetes patients.

Aging of alveolar type 2 cells induced by Lonp1 deficiency exacerbates pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic disease that significantly impacts patient quality of life, and its incidence is on the rise. The pathogenesis of IPF remains poorly understood. Alveolar type 2 (AT2) cells are crucial in the onset and progression of IPF, yet the specific mechanisms involved are not well defined. Lon protease 1 (LONP1), known for its critical roles in various diseases, has an unclear function in IPF. Our research investigated the impact of Lonp1 gene deletion on AT2 cell functionality and its subsequent effect on IPF development. We generated a bleomycin-induced pulmonary fibrosis mouse model with a targeted Lonp1 knockout in AT2 cells and assessed the consequences on AT2 cell function and fibrosis progression. Additionally, we constructed the MLE12 cells with stable Lonp1 knockdown and utilized transcriptome sequencing to identify pathways altered by the Lonp1 knockdown. Our results indicated that mice with AT2 cell-specific Lonp1 knockout exhibited more severe fibrosis compared to controls. These mice exhibited a reduction in AT2 and AT1 cell populations, along with an increase in p53- and p21-positive AT2 cells. Lonp1 knockdown in MLE12 cells led to the upregulation of aging-associated pathways, with fibroblast growth factor 2 (Fgf2) gene emerging as a central gene interconnecting these pathways. Therefore, loss of Lonp1 appears to promote AT2 cell aging and exacerbate bleomycin-induced pulmonary fibrosis. Fgf2 emerges as a pivotal downstream gene associated with cellular senescence. This study uncovers the role of the Lonp1 gene in pulmonary fibrosis, presenting a novel target for investigating the pathological mechanisms and potential therapeutic approaches for IPF.

Comparison of the efficacy of the convex side short fusion combined with concave side single growing rod technique and the traditional bilateral growing rod technique in the treatment of early onset scoliosis.

OBJECTIVES: The application of a growing rod technique can retain the growth and development potential of the spine and thorax while controlling the progression of scoliosis deformity. Theoretically, convex side short fusion combined with a concave side single growing rod technique can significantly reduce the asymmetric growth of the spine in the vertex region in most patients. However, the final clinical outcome of various techniques is yet to be clearly determined and compared between studies. Therefore, we compared the efficacy of these two growing rod techniques in treating early onset scoliosis. METHODS: In a retrospective study of 152 EOS patients seen between 2013.1 and 2019.12, 36 cases of EOS patients were selected for inclusion. Among the 36 cases, 11 cases were treated with convex side short fusion combined with a concave side single growing rod technique, group (A) The remaining 25 cases were treated with traditional bilateral growing rod technique, group (B) Age, gender, etiology, follow-up time, Cobb angle of main curve, T1-S1 height, coronal trunk shift, sagittal vertical axis (SVA), Cobb angle of thoracic kyphosis at last follow-up, and Cobb angle at proximal junction kyphosis of the first and last post-operation follow-up were recorded. In addition, internal fixation related complications, infection, nervous system complications were recorded as well. RESULTS: There was no statistically significant difference between group A and group B in preoperative age, Cobb angle of main curve, coronal trunk shift, T1-S1 height, SVA, Cobb angle of thoracic kyphosis (p > 0.05). However, at the last follow-up (Group A, mean 4.4 ± 1.01 years; Group B, mean 3.6 ± 0.01 years) the Cobb angle of the main curve was less and T1-S1 height greater in group A compared with group B (p < 0.05). There was no statistically significant difference between group A and group B in the correction rate of the Cobb angle of the main curve or the growth rate of T1-S1 height (p > 0.05). There was no statistically significant difference in the coronal imbalance ratio, thoracic kyphosis abnormality ratio, or the occurrence PJK ratio between group A and group B at the last follow-up (p > 0.05), but the sagittal imbalance ratio and internal fixation abnormality ratio were higher in group A than in the group B (p < 0.05). CONCLUSIONS: During the treatment of EOS, both the convex side short fusion combined with concave side single growing rod technique and traditional bilateral growing rod technique can correct the Cobb angle of main curve with no significant hindering of the spinal growth observed. The traditional bilateral growing rod technique has advantages in control of the sagittal balance of the spine, and the complications associated with internal fixation were lower.

Learning the cellular activity representation based on gene regulatory networks for prediction of tumor response to drugs.

Predicting the response of tumor cells to anti-tumor drugs is critical to realizing cancer precision medicine. Currently, most existing methods ignore the regulatory relationships between genes and thus have unsatisfactory predictive performance. In this paper, we propose to predict anti-tumor drug efficacy via learning the activity representation of tumor cells based on a priori knowledge of gene regulation networks (GRNs). Specifically, the method simulates the cellular biosystem by synthesizing a cell-gene activity network and then infers a new low-dimensional activity representation for tumor cells from the raw high-dimensional expression profile. The simulated cell-gene network mainly comprises known gene regulatory networks collected from multiple resources and fuses tumor cells by linking them to hotspot genes that are over- or under-expressed in them. The resulting activity representation could not only reflect the shallow expression profile (hotspot genes) but also mines in-depth information of gene regulation activity in tumor cells before treatment. Finally, we build deep learning models on the activity representation for predicting drug efficacy in tumor cells. Experimental results on the benchmark GDSC dataset demonstrate the superior performance of the proposed method over SOTA methods with the highest AUC of 0.954 in the efficacy label prediction and the best R2 of 0.834 in the regression of half maximal inhibitory concentration (IC50) values, suggesting the potential value of the proposed method in practice.

Compound SJ-12 attenuates streptozocin-induced diabetic cardiomyopathy by stabilizing SERCA2a.

Heart failure (HF) is one of the major causes of death among diabetic patients. Although studies have shown that curcumin analog C66 can remarkably relieve diabetes-associated cardiovascular and kidney complications, the role of SJ-12, SJ-12, a novel curcumin analog, in diabetic cardiomyopathy and its molecular targets are unknown. 7-week-old male C57BL/6 mice were intraperitoneally injected with single streptozotocin (STZ) (160 mg/kg) to develop diabetic cardiomyopathy (DCM). The diabetic mice were then treated with SJ-12 via gavage for two months. Body weight, fast blood glucose, cardiac utrasonography, myocardial injury markers, pathological morphology of the heart, hypertrophic and fibrotic markers were assessed. The potential target of SJ-12 was evaluated via RNA-sequencing analysis. The O-GlcNAcylation levels of SP1 were detected via immunoprecipitation. SJ-12 effectively suppressed myocardial hypertrophy and fibrosis, thereby preventing heart dysfunction in mice with STZ-induced heart failure. RNA-sequencing analysis revealed that SJ-12 exerted its therapeutic effects through the modulation of the calcium signaling pathway. Furthermore, SJ-12 reduced the O-GlcNAcylation levels of SP1 by inhibiting O-linked N-acetylglucosamine transferase (OGT). Also, SJ-12 stabilized Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase 2a (SERCA2a), a crucial regulator of calcium homeostasis, thus reducing hypertrophy and fibrosis in mouse hearts and cultured cardiomyocytes. However, the anti-fibrotic effects of SJ-12 were not detected in SERCA2a or OGT-silenced cardiomyocytes, indicating that SJ-12 can prevent DCM by targeting OGT-dependent O-GlcNAcylation of SP1.These findings indicate that SJ-12 can exert cardioprotective effects in STZ-induced mice by reducing the O-GlcNAcylation levels of SP1, thus stabilizing SERCA2a and reducing myocardial fibrosis and hypertrophy. Therefore, SJ-12 can be used for the treatment of diabetic cardiomyopathy.

A brief review of hybrid skin-topological effect.

The finding of non-Hermitian skin effect (NHSE) has revolutionized our understanding of non-Hermitian topological phases, where the usual bulk-boundary correspondence is broken and new topological phases specific to non-Hermitian system are uncovered. Hybrid skin-topological effect (HSTE) is a class of newly discovered non-Hermitian topological states that simultaneously supports skin-localized topological edge states and extended bulk states. Here we provide a brief review of HSTE, starting from different mechanisms that have been used to realize HSTE, including non-reciprocal couplings, onsite gain/loss, and non-Euclidean lattice geometries. We also review some theoretical developments closely related to the HSTE, including the concept of higher-order NHSE, parity-time symmetry engineering, and non-Hermitian chiral skin effect. Finally, we summarize recent experimental exploration of HSTE, including its realization in electric circuits systems, non-Hermitian photonic crystals, and active matter systems. We hope this review can make the concept of hybrid-skin effect clearer and inspire new finding of non-Hermitian topological states in higher dimensional systems.

Personalized anti-tumor drug efficacy prediction based on clinical data.

Anti-tumor drug efficacy prediction poses an unprecedented challenge to realizing personalized medicine. This paper proposes to predict personalized anti-tumor drug efficacy based on clinical data. Specifically, we encode the clinical text as numeric vectors featured with hidden topics for patients using Latent Dirichlet Allocation model. Then, to classify patients into two classes, responsive or non-responsive to a drug, drug efficacy predictors are established by machine learning based on the Latent Dirichlet Allocation topic representation. To evaluate the proposed method, we collected and collated clinical records of lung and bowel cancer patients treated with platinum. Experimental results on the data sets show the efficacy and effectiveness of the proposed method, suggesting the potential value of clinical data in cancer precision medicine. We hope that it will promote the research of drug efficacy prediction based on clinical data.

Evaluation of Effectiveness of Atorvastatin in Treating Chronic Subdural Hematoma not Requiring Surgery: A Meta-Analysis of Randomized Controlled Trials.

Chronic subdural hematoma (CSDH) is a chronic space-occupying lesion formed by blood accumulation between the arachnoid membrane and the dura mater. Atorvastatin is of increasing clinical interest for CSDH. We performed a meta-analysis of published randomized controlled trials (RCTs) and used objective data as the primary outcomes to provide an evidence-based analysis of the efficacy of atorvastatin for CSDH treatment. Databases of MEDLINE (via PubMed), EMBASE, the Cochrane Library, Scopus, Web of Science, ScienceDirect, Chinese National Knowledge Infrastructure (CNKI), Cqvip database (CQVIP), and Wanfang database were systematically searched for RCTs reporting the use of atorvastatin for CSDH treatment. Odds ratio (OR), standard mean difference (SMD), and 95% confidence intervals (CIs) were used as summary statistics. I-square (I2) test was performed to assess the impact of study heterogeneity on the results of the meta-analysis. Nine relevant RCTs with 611 patients were identified for inclusion in this meta-analysis. Compared to controls, atorvastatin treatment had a significantly higher effectiveness (OR: 7.41, 95% CI: 3.32-16.52, P < 0.00001, I2 = 0%), lower hematoma volume (SMD: -0.46. 95% CI: -0.71 to -0.20, P = 0.0005, I2 = 0%), higher activities of daily living-Barthel Index (ADL-BI) (SMD: 2.07, 95% CI: 1.06-3.09, P < 0.0001, I2 = 92%), and smaller Chinese stroke scale (CSS) (SMD: -1.10, 95% CI: -1.72 to -0.48, P = 0.0005, I2 = 57%). In view of these findings, we conclude that the outcomes of experimental group are superior to the control group with respect to effectiveness, hematoma volume, ADL-BI, and CSS based on nine RCTs with 611 patients. Atorvastatin is beneficial to CSDH patients without surgery.

Sitting Time Reduction and Blood Pressure in Older Adults: A Randomized Clinical Trial.

Importance: Practical health promotion strategies for improving cardiometabolic health in older adults are needed. Objective: To examine the efficacy of a sedentary behavior reduction intervention for reducing sitting time and improving blood pressure in older adults. Design, Setting, and Participants: This parallel-group randomized clinical trial was conducted in adults aged 60 to 89 years with high sitting time and body mass index of 30 to 50 from January 1, 2019, to November 31, 2022, at a health care system in Washington State. Intervention: Participants were randomized 1:1 to the sitting reduction intervention or a healthy living attention control condition for 6 months. Intervention participants received 10 health coaching contacts, sitting reduction goals, and a standing desk and fitness tracker to prompt sitting breaks. The attention control group received 10 health coaching contacts to set general healthy living goals, excluding physical activity or sedentary behavior. Main Outcomes and Measures: The primary outcome, measured at baseline, 3 months, and 6 months, was sitting time assessed using accelerometers worn for 7 days at each time point. Coprimary outcomes were systolic and diastolic blood pressure measured at baseline and 6 months. Results: A total of 283 participants (140 intervention and 143 control) were randomized (baseline mean [SD] age, 68.8 [6.2] years; 186 [65.7%] female; mean [SD] body mass index, 34.9 [4.7]). At baseline, 147 (51.9%) had a hypertension diagnosis and 97 (69.3%) took at least 1 antihypertensive medication. Sitting time was reduced, favoring the intervention arm, with a difference in the mean change of -31.44 min/d at 3 months (95% CI, -48.69 to -14.19 min/d; P < .001) and -31.85 min/d at 6 months (95% CI, -52.91 to -10.79 min/d; P = .003). Systolic blood pressure change was lower by 3.48 mm Hg, favoring the intervention arm at 6 months (95% CI, -6.68 to -0.28 mm Hg; P = .03). There were 6 serious adverse events in each arm and none were study related. Conclusions and Relevance: In this study of a 6-month sitting reduction intervention, older adults in the intervention reduced sedentary time by more than 30 min/d and reduced systolic blood pressure. Sitting reduction could be a promising approach to improve health in older adults. Trial Registration: ClinicalTrials.gov Identifier: NCT03739762.

Comparison of the applicability of seven calculation equations of glomerular filtration rate among elderly people in China.

BACKGROUND: At present, estimated glomerular filtration rate (eGFR) remains the most frequently utilized parameter in the evaluation of kidney injury severity. Numerous equations have been formulated based on serum creatinine (Scr) or serum cystatin C (Cysc) levels. However, there is a lack of consensus regarding the efficacy of these equations in assessing eGFR, particularly for elderly individuals in China. This study aimed to evaluate the applicability of the MDRD, MDRDc, CKD-EPI series, BIS1, and FAS equations within the Chinese elderly population. METHODS: A cohort of 298 elderly patients with measured GFR (mGFR) was enrolled. The patients were categorized into three subgroups based on their mGFR levels. The eGFR performance was examined, taking into account bias, interquartile range (IQR), accuracy P30, and root-mean-square error (RMSE). Bland-Altman plots were employed to verify the validity of eGFR. RESULTS: The participants had a median age of 71 years, with 167 (56.0%) being male. Overall, no significant differences in bias were observed among the seven equations (P > 0.05). In terms of IQR, P30, and RMSE, the BIS1 equation demonstrated superior accuracy (14.61, 72.1%, and 13.53, respectively). When mGFR < 30 ml/min/1.73 m2, all equations underestimated the true GFR, with the highest accuracy reaching only 59%. Bland-Altman plots indicated that the BIS1 equation exhibited the highest accuracy, featuring a 95% confidence interval (CI) width of 52.37. CONCLUSIONS: This study suggested that the BIS1 equation stands out as the most applicable for estimating GFR in Chinese elderly patients with normal renal function or only moderate decline. 2020NL-085-03, 2020.08.10, retrospectively registered.

Light-Activated BF3·Et2O-Promoted Generation of Singlet Oxygen and Cascade Reaction of Unsaturated Amides.

Herein, BF3·Et2O-promoted O-insertion/spirocyclization/fluorination/ring-expansion of unsaturated amides to synthesis of spiro[benzo[b]-[1,4]dioxepine-3,5'-oxazole] skeletons in the presence of natural light and O2 (3Σg-) was reported. Air was the oxygen source of the 1O2-generation and O-insertion reaction under metal-free and mild conditions. BF3·Et2O played multiple roles, such as Lewis acid, activating reagent, and fluorine source in the reported cascade. A mechanism involving 1O2 generation/activation of double bond/O-insertion/spirocyclization/fluorination/ring expansion was supposed.

Ce/N @BC prepared based on plant metallurgy strategy: A novel activator of peroxymonosulfate for the degradation of sulfamethoxazole.

A novel carbon catalyst was created based on plant metallurgy strategy for organic pollutants removal. Plants rich in CeO2 NPs in water were used as carbon precursors and pyrolyzed with urea to obtain Ce/N co-doped carbon catalysts, which were used in the degradation of sulfamethoxazole (SMX) by active peroxymonosulfate (PMS). The results showed that the Ce/N @BC/PMS system achieved to 94.5% degradation of SMX in 40 min at a rate constant of 0.0602 cm-1. The activation center of PMS is widely dispersed Ce oxide nanocrystals, and CeO2 NPs promote the formation of oxygen centered PFR with enhanced catalytic ability and longer half-life. In addition, N-doping facilitates the transfer of π-electrons within the sp2 carbon of biochar, increasing active sites and thus improving PMS activation efficiency. The degradation process was contributed to by both radical and non-radical activation mechanisms including 1O2 and direct electron transfer, with O2•- serving as 1O2's precursor. Through the DFT calculations, LC-MS and toxicological analyses, the degradation pathway of pollutants and the toxicity changes throughout the entire degradation process were further revealed, indicating that the degradation of SMX could effectively reduce ecological toxicity.

GTS-21 attenuates ACE/ACE2 ratio and glycocalyx shedding in lipopolysaccharide-induced acute lung injury by targeting macrophage polarization derived ADAM-17.

Acute lung injury (ALI) has received considerable attention in intensive care owing to its high mortality rate. It has been demonstrated that the selective alpha7 nicotinic acetylcholine receptor agonist Gainesville Tokushima scientists (GTS)-21 is promising for treating ALI caused by lipopolysaccharides (LPS). However, the precise underlying mechanism remains unknown. This study aimed to investigate the potential efficacy of GTS-21 in the treatment of ALI. We developed mouse models of ALI and alveolar epithelial type II cells (AT2s) injury following treatment with LPS and different polarized macrophage supernatants, respectively. Pathological changes, pulmonary edema, and lung compliance were assessed. Inflammatory cells count, protein content, and pro-inflammatory cytokine levels were analysed in the bronchoalveolar lavage fluid. The expression of angiotensin-converting enzyme (ACE), ACE2, syndecan-1 (SDC-1), heparan sulphate (HS), heparanase (HPA), exostosin (EXT)-1, and NF-κB were tested in lung tissues and cells. GTS-21-induced changes in macrophage polarization were verified in vivo and in vitro. Polarized macrophage supernatants with or without recombination a disintegrin and metalloproteinase-17 (ADAM-17) and small interfering (si)RNA ADAM-17 were used to verify the role of ADAM-17 in AT2 injury. By reducing pathological alterations, lung permeability, inflammatory response, ACE/ACE2 ratio, and glycocalyx shedding, as well as by downregulating the HPA and NF-κB pathways and upregulating EXT1 expression in vivo, GTS-21 significantly diminished LPS-induced ALI compared to that of the LPS group. GTS-21 significantly attenuated macrophage M1 polarization and augmented M2 polarization in vitro and in vivo. The destructive effects of M1 polarization supernatant can be inhibited by GTS-21 and siRNA ADAM-17. GTS-21 exerted a protective effect against LPS-induced ALI, which was reversed by recombinant ADAM-17. Collectively, GTS-21 alleviates LPS-induced ALI by attenuating AT2s ACE/ACE2 ratio and glycocalyx shedding through the inhibition of macrophage M1 polarization derived ADAM-17.

Vasoactive-Inotropic Score as a Promising Predictor of Acute Kidney Injury in Adult Patients Requiring Extracorporeal Membrane Oxygenation.

Acute kidney injury (AKI) is a common complication in patients supported by extracorporeal membrane oxygenation (ECMO). Vasoactive-Inotropic Score (VIS) serves as an indicator of the extent of cardiovascular drug support provided. Our objective is to assess the relationship between the VIS and ECMO-associated AKI (EAKI). This single-center retrospective study extracted adult patients treated with ECMO between August 2016 and September 2022 from an intensive care unit (ICU) in a university hospital. A total of 126 patients requiring ECMO support were included in the study, of which 76% developed AKI. Multivariate logistic regression analysis identified VIS-max Day1 (odds ratio [OR]: 1.025, 95% confidence interval [CI]: 1.007-1.044, p = 0.006), VIS-max Day2 (OR: 1.038, 95% CI: 1.007-1.069, p = 0.015), VIS-mean Day1 (OR: 1.048, 95% CI: 1.013-1.084, p = 0.007), and VIS-mean Day2 (OR: 1.059, 95% CI: 1.014-1.107, p = 0.010) as independent risk factors for EAKI. VIS-max Day1 showing the best predictive effect (Area under the receiver operating characteristic curve (AUROC): 0.80, sensitivity: 71.87%, specificity: 80.00%) for EAKI with a cutoff value of 33.33. Surprisingly, VIS-mean Day2 was also excellent at predicting 7 day mortality (AUROC: 0.77, sensitivity: 87.50%, specificity: 56.38%) with a cutoff value of 8.67. In conclusion, VIS could independently predict EAKI and 7 day mortality in patients with ECMO implantation, which may help clinicians to recognize the poor prognosis in time for early intervention.