Recurrent quantum embedding neural network and its application in vulnerability detection.

In recent years, deep learning has been widely used in vulnerability detection with remarkable results. These studies often apply natural language processing (NLP) technologies due to the natural similarity between code and language. Since NLP usually consumes a lot of computing resources, its combination with quantum computing is becoming a valuable research direction. In this paper, we present a Recurrent Quantum Embedding Neural Network (RQENN) for vulnerability detection. It aims to reduce the memory consumption of classical models for vulnerability detection tasks and improve the performance of quantum natural language processing (QNLP) methods. We show that the performance of RQENN achieves the above goals. Compared with the classic model, the space complexity of each stage of its execution is exponentially reduced, and the number of parameters used and the number of bits consumed are significantly reduced. Compared with other QNLP methods, RQENN uses fewer qubit resources and achieves a 15.7% higher accuracy in vulnerability detection.

Inflammation and coronary microvascular disease: relationship, mechanism and treatment.

Coronary microvascular disease (CMVD) is common in patients with cardiovascular risk factors and is linked to an elevated risk of adverse cardiovascular events. Although modern medicine has made significant strides in researching CMVD, we still lack a comprehensive understanding of its pathophysiological mechanisms due to its complex and somewhat cryptic etiology. This greatly impedes the clinical diagnosis and treatment of CMVD. The primary pathological mechanisms of CMVD are structural abnormalities and/or dysfunction of coronary microvascular endothelial cells. The development of CMVD may also involve a variety of inflammatory factors through the endothelial cell injury pathway. This paper first reviews the correlation between the inflammatory response and CMVD, then summarizes the possible mechanisms of inflammatory response in CMVD, and finally categorizes the drugs used to treat CMVD based on their effect on the inflammatory response. We hope that this paper draws attention to CMVD and provides novel ideas for potential therapeutic strategies based on the inflammatory response.

A new fossil species of Meliolinites Selkirk associated with Rhodoleia leaves from the Upper Pliocene of southwestern China.

Fossil epifoliar fungi are valuable indicators of paleoenvironment and paleoecology. The Meliolaceae, members of which typically inhabit the surface of living plants as biotrophs or pathogens, is one of the largest groups of epifoliar fungi. In this study, we report a novel fossil species of Meliolinites Selkirk (fossil Meliolaceae), Meliolinites tengchongensis, on the lower epidermis of compressed fossil Rhodoleia (Hamamelidaceae) leaves from the Upper Pliocene Mangbang Formation of Tengchong, Yunnan, southwestern China. Meliolinites tengchongensis is characterized by web-like, superficial, brown to dark brown, septate, and branching mycelia bearing 2-celled appressoria and unicellular phialides. The fungal colonies also include ellipsoidal, 5-celled, 4-septate ascospores and dark brown perithecia with suborbicular outline and verrucose surface. The well-preserved vegetative and reproductive organs help us to explore the potential disease process of the new fossil species. Besides, the presence of fungal remains indicates that the fungal taxon might have maintained its host preference since at least the Late Pliocene. Furthermore, the occurrence of both fossil fungi and their host plants in Tengchong indicate a subtropical-tropical, warm, and humid climate during the Late Pliocene, whereas the distribution pattern of the fungi on the host leaves suggests that Rhodoleia may have been a part of the middle-upper canopies in the Tengchong Late Pliocene multilayered forest.

An observational study on the safety of teprotumumab based on FAERS database.

OBJECTIVE: Teprotumumab plays an important role in thyroid eye disease pathogenesis and progression. We intend to mine the adverse event (AE) signals from a relevant database, thereby contributing to the safe use of teprotumumab. METHODS: The data obtained from the ASCII data packages in the FAERS database from January 2020 to the second quarter of 2023 were imported into the SAS software (version 9.4) for data cleaning and analysis. Disproportionality analysis was performed using the reporting odds ratio (ROR) in conjunction with the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) omnibus standard method to detect positive signals. PARTICIPANTS: This retrospective observational study relied on adverse drug reactions reported to the FDA through FAERS, which is a standard public system for spontaneous reporting. RESULTS: Collectively, 2171 AE reports for teprotumumab were collected, among which 108 significant signals were identified involving 17 system organ classes. The SOC of ear and labyrinth disorders included the most AE signals and reports. Muscle spasms, fatigue, headache, nausea, diarrhea, alopecia, blood glucose increased, hypoacusis, tinnitus, and diabetes mellitus were the top ten PTs ranked by the frequency of reporting, meanwhile, the two high-strength signals of thyroid-stimulating immunoglobulin increase (ROR 662.89, 95% CI 182.40-2409.19) and gingival recession (ROR 125.13, 95% CI 79.70-196.45) were not documented in the drug instruction. Meanwhile, we found a higher risk of increased blood glucose, deafness, and decreased appetite for male patients, and headache for female patients. CONCLUSIONS: Clinical application of teprotumumab should be closely monitored for ototoxicity, nail abnormalities, and menstrual changes, as well as for AEs not mentioned in the drug instruction, including gingival recession, thyroid-stimulating immunoglobulin increase, and so on.

The Effect of Antihyperglycemic Medications on COVID-19: A Meta-analysis and Systematic Review from Observational Studies.

BACKGROUND: Diabetes, a chronic disease worldwide, may be associated with a poorer prognosis in patients with coronavirus disease 2019 (COVID-19). While some antihyperglycemic medications may be beneficial, others may increase the risk of adverse clinical outcomes of COVID-19. We aimed to analyze the effect of antihyperglycemic medications on COVID-19. METHODS: We searched the Web of Science, Cochrane Library, EMBASE, PubMed, and Scopus databases from December 2019 to June 2022 to identify literature related to patients with COVID-19 and type 2 diabetes mellitus (T2DM) treated with antihyperglycemic medications. RESULTS: 56 studies were included in the analysis. Metformin (OR 0.66; 95% CI 0.58-0.74; p < 0.05), Glucagon-like peptide-1 receptor agonist (GLP-1ra) (OR 0.73; 95% CI 0.59-0.91; p < 0.05), and sodium-dependent glucose transporters 2 inhibitor (SGLT 2i) (OR 0.77; 95% CI 0.69-0.87; p < 0.05) were associated with lower mortality risk, while insulin was associated with increased mortality risk (OR 1.40; 95% CI 1.26-1.55; p < 0.05). Meanwhile, metformin (OR 0.65; 95% CI 0.50-0.85; p < 0.05) and GLP-1ra (OR 0.84; 95% CI 0.76-0.94; p < 0.05) were significantly associated with decreased severe manifestation risk. What's more, metformin (OR 0.77; 95% CI 0.62-0.96; p < 0.05), GLP-1ra (OR 0.86; 95% CI 0.81-0.92; p < 0.05), and SGLT 2i (OR 0.87; 95% CI 0.79-0.97; p < 0.05) were also associated with a decreased risk of hospitalization, but insulin were associated with an increased risk of hospitalization (OR 1.31; 95% CI 1.12-1.52; p < 0.05). Nevertheless, the results of the subgroup analyses showed that the effects of different glucose-lowering agents on COVID-19 may be related to in-hospital use or out-hospital use, elderly or non-elderly patients use, and different geography. CONCLUSION: Metformin, GLP-1ra, and SGLT 2i have shown a positive effect on clinical outcomes in COVID-19, particularly in non-elderly individuals. However, insulin use may pose a higher risk, especially in elderly patients, so need with caution. Meanwhile, DPP-4i, TZD, α-GLUi, and sulfonylureas appeared to have a neutral effect. These results need to be validated in future clinical studies.

Nickel-Catalyzed Ethylene Copolymerization with Vinylalkoxysilanes: A Computational Study.

Since the discovery of α-diimine catalysts in 1995, an extensive series of Brookhart-type complexes have shown their excellence in catalyzing ethylene polymerizations with remarkable activity and a high molecular weight. However, although this class of palladium complexes has proven proficiency in catalyzing ethylene copolymerization with various polar monomers, the α-diimine nickel catalysts have generally exhibited a much worse performance in these copolymerizations compared to their palladium counterparts. Recently, Brookhart et al. reported a notable exception, demonstrating that α-diimine nickel catalysts could catalyze the ethylene copolymerization with some vinylalkoxysilanes effectively, producing functionalized polyethylene incorporating trialkoxysilane (-Si(OR)3) groups. This breakthrough is significant since Pd-catalyzed copolymerizations are commercially less usable due to the high cost of palladium. Thus, the utilization of Ni, given its abundance in raw materials and cost-effectiveness, is a landmark in ethylene/polar vinyl monomer copolymerization. Inspired by these findings, we used density functional theory (DFT) calculations to investigate the mechanistic study of ethylene copolymerization with vinyltrimethoxysilane (VTMoS) catalyzed by Brookhart-type nickel catalysts, aiming to elucidate the molecular-level understanding of this unique reaction. Initially, the nickel complexes and cationic active species were optimized through DFT calculations. Subsequently, we explored the mechanisms including the chain initiation, chain propagation, and chain termination of ethylene homopolymerization and copolymerization catalyzed by Brookhart-type complexes. Finally, we conducted an energetic analysis of both the in-chain and chain-end of silane enchainment. It was found that chain initiation is the dominant step in the ethylene homopolymerization catalyzed by the α-diimine Ni complex. The 1,2- and 2,1-insertion of vinylalkoxysilane exhibit similar barriers, explaining the fact that both five-membered and four-membered chelates were identified experimentally. After the VTMoS insertion, the barriers of ethylene reinsertion become higher, indicating that this step is the rate-determining step, which could be attributed to the steric hindrance between the incoming ethylene and the bulky silane substrate. We have also reported the energetic analysis of the distribution of polar substrates. The dominant pathway of chain-end -Si(OR)3 incorporation is suggested as chain-walking → ring-opening → ethylene insertion, and the preference of chain-end -Si(OR)3 incorporation is primarily attributed to the steric repulsion between the pre-inserted silane group and the incoming ethylene molecule, reducing the likelihood of in-chain incorporation.

Evaluating the impact of the innovation efficiency of high-tech industry on carbon emissions: a case study of the manufacturing industry in China.

Amid China's economic shift to high-quality development, addressing environmental challenges like greenhouse gas emissions and manufacturing pollution, there is a crucial demand for sustainable and eco-friendly development strategies. This study aims to investigate the impact of innovation efficiency in the high-tech industry on carbon emissions. It seeks to explore regional differences, mechanisms, and the influence of energy consumption structures in achieving sustainable development goals. Utilizing data from 30 provinces spanning 2009 to 2020, the study employs the DEA-Malmquist index model, spatial and temporal classification evaluation, and a panel measurement model to assess the efficiency of innovation and development in high-tech industries and their relationship with carbon emissions. The results indicate several key findings: (1) The overall operational efficiency of high-tech industry innovation and development in China is steadily increasing. However, there are distinct characteristics observed among provinces and cities, reflecting diverse input and output types. (2) High-tech industry innovation efficiency significantly contributes to carbon emission reduction, and there is regional heterogeneity in this impact. The central and western regions exhibit greater effects compared to other provinces and cities. (3) The optimization of the energy structure is identified as a mechanism through which high-tech industry innovation efficiency reduces carbon emissions. Moreover, different intervals of high-tech industry innovation efficiency yield varying effects on carbon emissions. This research underscores the importance of fostering high-tech industry innovation efficiency as a means to reduce carbon emissions. It also identifies key areas for future policy development and resource allocation, emphasizing the support needed for low-carbon technology research and development.

Experimental and Theoretical Insights into the Effect of Dioldibenzoate Isomers on the Performance of Polypropylene Catalysts.

Experimental investigations and density functional theory (DFT) calculations were carried out to study the comprehensive effect of different 3,5-heptanedioldibenzoate (HDDB) optical isomers as the internal electron donor on the catalytic performance of Ziegler-Natta catalysts. The experimental catalytic activity of HDDB has a positive correlation with the relative content of the mesomer incorporated during catalyst preparation, while the hydrogen response of HDDB displayed a negative correlation with the relative content of the mesomer. In order to apply the DFT calculation results to the macroscopic activity of the catalyst, the content of the active centers of the catalyst was analyzed. Assuming that the content of the active centers is proportional to the internal electron donor content of the catalyst, binary linear regression was carried out, which showed a good linear correlation between experimental activity data and internal electron donor content. Furthermore, the fitted activity of the single active centers aligned well with the calculated activation energies. These results revealed that the catalytic activity of polypropylene (PP) catalysts is dependent on both the active center content and the catalytic activity of an individual active center. Additionally, the lower hydrogen response of HDDB leads to a higher molecular weight of polypropylene obtained from the RS-containing catalyst compared to the SS-containing catalyst. Further study reveals that the hydrogen transfer reactions of 2,4-pentanediol dibenzoate (PDDB)/HDDB are influenced by the orientation of the methyl/ethyl groups in different isomers, which affect the activation energy differences between the hydrogen transfer reaction and the propylene insertion reaction, and finally influence the molecular weight of PP.

MicroRNA-195-5p Attenuates Pregnancy-Induced Hypertension by Inhibiting Oxidative Stress via OTX1/MAPK Signaling Pathway.

Pregnancy-induced hypertension (PIH) is a hypertensive disorder during pregnancy and can induce perinatal death of human infants. MicroRNA (miR)-195-5p was validated to display low expression in severe preeclampsia placentas, but the role of miR-195-5p in pregnancy-induced hypertension (PIH) has not been investigated. The study emphasized on the functions and mechanism of miR-195-5p in PIH. A reduced uterine perfusion pressure (RUPP) rat model was established to mimic PIH in vivo. Adenovirus (Ad)-miR-195-5p agomir and/or Ad-OTX1 were further injected into some model rats. RT-qPCR was conducted to assess the expression of miR-195-5p and orthodenticle homeobox 1 (OTX1) in rat placental tissues, the isolated aortic endothelial cells (AECs), and in serum samples of PIH patients. Western blot analysis was implemented to measure the protein levels of OTX1, VEGFA, and key factors involved in the MAPK signaling pathway. The concentrations of oxidative stress markers (superoxide dismutase, catalase, and lipid hydroperoxide) in AECs and placental tissues of RUPP rats were measured by corresponding kits. The binding relation between miR-195-5p and OTX1 was verified using the dual-luciferase reporter assay. Hematoxylin-eosin staining was conducted to evaluate the pathological features of rat placental tissues. MiR-195-5p was downregulated, while OTX1 was upregulated in rat placental tissues and human serum samples of PIH patients. MiR-195-5p could target OTX1 and inversely regulate OTX1 expression in AECs and rat placental tissues. In addition, miR-195-5p can negatively regulate VEGFA level. Furthermore, miR-195-5p inactivates oxidative stress and the MAPK signaling by downregulating OTX1 in AECs. In vivo experiments revealed that OTX1 overexpression reversed the protective effect of miR-195-5p overexpression on placental damage and oxidative stress. MiR-195-5p alleviates PIH by inhibiting oxidative stress via targeting OTX1 and inactivating MAPK signaling.

Potential mechanism of Qinggong Shoutao pill alleviating age-associated memory decline based on integration strategy.

CONTEXT: Qinggong Shoutao Wan (QGSTW) is a pill used as a traditional medicine to treat age-associated memory decline (AAMI). However, its potential mechanisms are unclear. OBJECTIVE: This study elucidates the possible mechanisms of QGSTW in treating AAMI. MATERIALS AND METHODS: Network pharmacology and molecular docking approaches were utilized to identify the potential pathway by which QGSTW alleviates AAMI. C57BL/6J mice were divided randomly into control, model, and QGSTW groups. A mouse model of AAMI was established by d-galactose, and the pathways that QGSTW acts on to ameliorate AAMI were determined by ELISA, immunofluorescence staining and Western blotting after treatment with d-gal (100 mg/kg) and QGSTW (20 mL/kg) for 12 weeks. RESULTS: Network pharmacology demonstrated that the targets of the active components were significantly enriched in the cAMP signaling pathway. AKT1, FOS, GRIN2B, and GRIN1 were the core target proteins. QGSTW treatment increased the discrimination index from -16.92 ± 7.06 to 23.88 ± 15.94% in the novel location test and from -19.54 ± 5.71 to 17.55 ± 6.73% in the novel object recognition test. ELISA showed that QGSTW could increase the levels of cAMP. Western blot analysis revealed that QGSTW could upregulate the expression of PKA, CREB, c-Fos, GluN1, GluA1, CaMKII-α, and SYN. Immunostaining revealed that the expression of SYN was decreased in the CA1 and DG. DISCUSSION AND CONCLUSIONS: This study not only provides new insights into the mechanism of QGSTW in the treatment of AAMI but also provides important information and new research ideas for the discovery of traditional Chinese medicine compounds that can treat AAMI.

Recent Advancements in Mechanistic Studies of Palladium- and Nickel-Catalyzed Ethylene Copolymerization with Polar Monomers.

The introduction of polar functional groups into polyolefin chain structures creates opportunities to enhance specific properties, such as adhesion, dyeability, printability, compatibility, thermal stability, and electrical conductivity, which widen the range of potential applications for these modified materials. Transition metal catalysts, especially late transition metals, have proven to be highly effective in copolymerization processes due to their reduced Lewis acidity and electrophilicity. However, when compared to the significant progress and summary of synthetic methods, there is a distinct lack of a comprehensive summary of mechanistic studies pertaining to the catalytic systems involved in ethylene copolymerization catalyzed by palladium and nickel catalysts. In this review, we have provided a comprehensive summary of the latest developments in mechanistic studies of ethylene copolymerization with polar monomers catalyzed by late-transition-metal complexes. Experimental and computational methods were employed to conduct a detailed investigation of these organic and organometallic systems. It is mainly focused on ligand substitution, changes in binding modes, ethylene/polar monomer insertion, chelate opening, and ß-H elimination. Factors that control the catalytic activity, molecular weight, comonomer incorporation ratios, and branch content are analyzed, these include steric repulsions between ligands and monomers, electronic effects arising from both ligands and monomers, and so on.

Targeting mitochondrial circadian rhythms: The potential intervention strategies of Traditional Chinese medicine for myocardial ischaemia‒reperfusion injury.

Coronary artery disease has one of the highest mortality rates in the country, and methods such as thrombolysis and percutaneous coronary intervention (PCI) can effectively improve symptoms and reduce mortality, but most patients still experience symptoms such as chest pain after PCI, which seriously affects their quality of life and increases the incidence of adverse cardiovascular events (myocardial ischaemiareperfusion injury, MIRI). MIRI has been shown to be closely associated with circadian rhythm disorders and mitochondrial dysfunction. Mitochondria are a key component in the maintenance of normal cardiac function, and new research shows that mitochondria have circadian properties. Traditional Chinese medicine (TCM), as a traditional therapeutic approach characterised by a holistic concept and evidence-based treatment, has significant advantages in the treatment of MIRI, and there is an interaction between the yin-yang theory of TCM and the circadian rhythm of Western medicine at various levels. This paper reviews the clinical evidence for the treatment of MIRI in TCM, basic experimental studies on the alleviation of MIRI by TCM through the regulation of mitochondria, the important role of circadian rhythms in the pathophysiology of MIRI, and the potential mechanisms by which TCM regulates mitochondrial circadian rhythms to alleviate MIRI through the regulation of the biological clock transcription factor. It is hoped that this review will provide new insights into the clinical management, basic research and development of drugs to treat MIRI.

Experimental and Computational Studies on Cobalt(I)-Catalyzed Regioselective Allylic Alkylation Reactions.

Here, we report the development of cobalt(I)-catalyzed regioselective allylic alkylation reactions of tertiary allyl carbonates with 1,3-dicarbonyl compounds. A family of well-defined tetrahedral cobalt(I) complexes bearing commercially available bidentate bis(phosphine) ligands [(P,P)Co(PPh3 )Cl] are synthesized and explored as catalysts in allylic alkylation reactions. The catalyst [(dppp)Co(PPh3 )Cl] (dppp=1,3-Bis(diphenylphosphino)propane) enables the alkylation of a large variety of tertiary allyl carbonates with high yields and excellent regioselectivity for the branched product. Remarkably, this methodology is selective for the activation of tertiary allyl carbonates even in the presence of secondary allyl carbonates. This contrasts with the selectivity observed in cobalt-catalyzed allylic alkylations enabled by visible light photocatalysis. Mechanistic insights by means of experimental and computational investigations support a Co(I)/Co(III) catalytic cycle.

Targeting metabolic pathways: a novel therapeutic direction for type 2 diabetes.

Background: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease that causes multi-organ complications, seriously affecting patients' quality of life and survival. Understanding its pathogenesis remains challenging, with current clinical treatment regimens often proving ineffective. Methods: In this study, we established a mouse model of T2DM and employed 16s rDNA sequencing to detect changes in the species and structure of gut flora. Additionally, we used UPLC-Q-TOF-MS to identify changes in urinary metabolites of T2DM mice, analyzed differential metabolites and constructed differential metabolic pathways. Finally, we used Pearman correlation analysis to investigate the relationship between intestinal flora and differential metabolites in T2DM mice, aiming to elucidate the pathogenesis of T2DM and provide an experimental basis for its clinical treatment. Results: Our findings revealed a reduction in both the species diversity and abundance of intestinal flora in T2DM mice, with significantly decreased levels of beneficial bacteria such as Lactobacillus and significantly increased levels of harmful bacteria such as Helicobacter pylori. Urinary metabolomics results identified 31 differential metabolites between T2DM and control mice, including Phosphatidylcholine, CDP-ethanolamine and Leukotriene A4, which may be closely associated with the glycerophospholipid and arachidonic acid pathways. Pearman correlation analysis showed a strong correlation between dopamine and gonadal, estradiol and gut microbiota, may be a novel direction underlying T2DM. Conclusion: In conclusion, our study suggests that alterations in gut microbiota and urinary metabolites are characteristic features of T2DM in mice. Furthermore, a strong correlation between dopamine, estradiol and gut microbiota, may be a novel direction underlying T2DM, the aim is to provide new ideas for clinical treatment and basic research.

An overview of limonoid synthetic derivatives as promising bioactive molecules.

Limonoids, a class of abundant natural tetracyclic triterpenoids, present diverse biological activity and provide a versatile platform amenable by chemical modifications for clinical use. Among all of the limonoids isolated from natural sources, obacunone, nomilin, and limonin are the primary hub of limonoid-based chemical modification research. To date, more than 800 limonoids analogs have been synthesized, some of which possess promising biological activities. This review not only discusses the synthesis of limonoid derivatives as promising therapeutic candidates and details the pharmacological studies of their underlying mechanisms from 2002 to 2022, but also proposes a preliminary limonoid synthetic structure-activity relationship (SAR) and provides future direction of limonoid derivatization research.

Chinese patent medicines for coronary microvascular disease: clinical evidence and potential mechanisms.

Coronary microvascular disease (CMVD) is a high risk factor for many cardiovascular events. Due to the limited understanding of its pathophysiological mechanism, modern medicine still lacks therapeutic drugs for CMVD. Existing clinical studies have shown that traditional Chinese medicine (TCM) can effectively improve the clinical symptoms and quality of life of CMVD patients. As an indispensable part of TCM, Chinese patent medicines (CPMs) are widely used in clinical practice. In the face of numerous oral CPMs for treatment of CMVD, how to choose a reasonable medication regimen is one of the important issues in clinic. Based on this, this paper reviewed the clinical efficacy and recommended level of 12 CPMs in the treatment of CMVD, which are recommended by expert consensus on diagnosis and treatment of coronary microvascular disease with integrated Chinese and Western medicine (WM). In addition, this study also systematically summarized the possible mechanisms of CPMs in the treatment of CMVD by protecting coronary microvascular endothelial cells, improving vascular endothelial function, inhibiting inflammation, reducing oxidative stress, promoting angiogenesis, and improving hemorheology, aiming to provide meaningful information for its clinical application.

Impact of a multifaceted intervention on non-guideline-recommended prescribing of acid suppressive medications for stress ulcer prophylaxis in critically ill patients.

OBJECTIVE: To promote an effective strategy to improve the non-guideline-recommended prescribing (NGRP) of acid suppressive medications for stress ulcer prophylaxis (SUP) in critically ill patients and to evaluate the impact and barriers of a multifaceted intervention on NGRP in critically ill patients. RESEARCH DESIGN AND METHODS: A retrospective, pre- post-intervention study was performed in the medical-surgical ICU. This study included pre-intervention and post-intervention period. There was no SUP guideline and intervention in the pre-intervention period. In the post-intervention period, the multifaceted intervention included five features: a practice guideline, an education campaign, medication review and recommendations, medication reconciliation, and pharmacist rounding with the ICU team. RESULTS: A total of 557 patients were studied (305 in the pre-intervention group and 252 in the post-intervention group). Patients who underwent surgery, stayed in ICU more than 7 days, or used corticosteroids experienced significantly higher rate of NGRP in the pre-intervention group. The average percentage of patient days of NGRP was significantly reduced from 44.2% to 23.5% (p < .001) by implementing the multifaceted intervention. The percentage of patients with NGRP decreased from 86.7% to 45.5% in terms of all 5 criteria (indication, dosage, IV to PO, duration, and ICU discharge; p = .003). Per-patient NGRP cost decreased from $45.1 (22.6, 93.0) to $11.3 (11.3, 45.1; p = .004). The main barrier influencing NGRP was the factors of the patient, including the concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs), the number of comorbidities, and undergoing surgery. CONCLUSION: The multifaceted intervention was effective in improving NGRP. Further studies are needed to confirm whether our strategy is cost-effective.

Neuroprotective Effects of Dammarane Sapogenins Against lipopolysaccharide-induced Cognitive Impairment, Neuroinflammation and Synaptic Dysfunction.

Neuroinflammation is a critical driver in the pathogenesis and progression of neurodegenerative disorders. Dammarane sapogenins (DS), a deglycosylated product of ginsenoside, possess a variety of potent biological activities. The present study aimed to explore the neuroprotective effects of DS in a rat model of neuroinflammation induced by intracerebroventricular injection of lipopolysaccharide (LPS). Our study revealed that DS pretreatment effectively improved LPS-induced associative learning and memory impairments in the active avoidance response test and spatial learning and memory in Morris water maze test. DS also remarkably inhibited LPS-induced neuroinflammation by suppressing microglia overactivation, pro-inflammatory cytok ine release (TNF-α and IL-1ß) and reducing neuronal loss in the CA1 and DG regions of the hippocampus. Importantly, pretreatment with DS reversed LPS-induced upregulation of HMGB1 and TLR4 and inhibited their downstream NF-κB signaling activation, as evidenced by increased IκBα and decreased p-NF-κB p65 levels. Furthermore, DS ameliorated LPS-induced synaptic dysfunction by decreasing MMP-9 and increasing NMDAR1 expression in the hippocampus. Taken together, this study suggests that DS could be a promising treatment for preventing cognitive impairments caused by neuroinflammation.

Impact of ectopic fat on brain structure and cognitive function: A systematic review and meta-analysis from observational studies.

Ectopic fat, defined as a specific organ or compartment with the accumulation of fat tissue surrounding organs, is highly associated with obesity which has been identified as a risk factor for cognitive impairment and dementia. However, the relationship between ectopic fat and changes in brain structure or cognition is yet to be elucidated. Here, we investigated the effects of ectopic fat on brain structure and cognitive function via systemic review and meta-analysis. A total of 21 studies were included from electronic databases up to July 9, 2022. We found ectopic fat was associated with decreased total brain volumeand increased lateral ventricle volume. In addition, ectopic was associated with decreased cognitive scores and negatively correlated with cognitive function. More specifically, dementia development were correlated with increased levels of visceral fat. Overall, our data suggested that increased ectopic fat was associated with prominent structural changes in the brain and cognitive decline, an effect driven mainly by increases in visceral fat, while subcutaneous fat may be protective. Our results suggest that patients with increased visceral fat are at risk of developing cognitive impairment and, therefore, represent a subset of population in whom appropriate and timely preventive measures could be implemented.

Comparison of antivascular endothelial growth factor treatment for myopia choroidal neovascularisation: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To evaluate the efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) therapy for myopia choroidal neovascularisation (CNV), and to compare the efficacy of two different anti-VEGF retreatment criteria. DATA SOURCES: PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched from inception to 31 July 2022. STUDY SELECTION: Randomised controlled trials (RCTs) comparing anti-VEGF with sham, photodynamic therapy (PDT) or PDT combination therapy in patients with myopia CNV were reviewed and selected. RCTs comparing visual acuity (VA) stabilisation or disease activity as anti-VEGF retreatment criteria were also included in the study. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently conducted data extraction and quality assessment. We used a random-effects model for all analyses. Primary outcomes included best-corrected visual acuity (BCVA) and central foveal thickness. Secondary outcomes included number of patients who gained more than three lines in BCVA, number of anti-VEGF injections and ocular adverse event (AE). RESULTS: Seven RCTs involving 1007 patients were included. Compared with sham and PDT therapy, anti-VEGF therapy achieved better BCVA gains of -0.28 logMAR (95% CI -0.36 to -0.20, p<0.00001) and -0.14 logMAR (95% CI -0.17 to -0.10, p<0.00001), respectively. Both ranibizumab and bevacizumab improved patients' vision better than PDT therapy and no definitive increased risk of ocular AE was observed. Analysis of two small RCTs showed that PDT combination therapy had similar visual improvement and needed fewer anti-VEGF injections compared with anti-VEGF monotherapy (weighted mean difference (WMD)=1.30; 95% CI 1.24 to 1.37, p<0.00001). Anti-VEGF retreatment guided by disease activity criteria resulted in comparable visual improvement and reduced anti-VEGF injections compared with retreatment guided by VA stabilisation (WMD=0.83; 95% CI 0.42 to 1.25, p<0.0001). CONCLUSIONS: Anti-VEGF therapy is effective and well-tolerated for myopia CNV patients. Anti-VEGF retreatment guided by disease activity criteria can achieve comparable efficacy and potentially reduce anti-VEGF injections. PROSPERO REGISTRATION NUMBER: CRD42021292806.