Role of ferroptosis in Porphyromonas gingivalis-induced impairment of epithelial junction.

Objectives: This study aims to clarify the effect of ferroptosis by P. gingivalis on periodontal epithelium impairment and potential mechanisms. Materials and methods: The expression of epithelial junction proteins (CDH1, OCLN, ZO-1), FTL and GPX4 in healthy and periodontitis tissues was analyzed using bioinformatics analysis and validated in vivo. An in vitro model was constructed to evaluate ferroptosis by mitochondria morphology, content of iron and GSH, and level of lipid peroxidation, FTL, GPX4 and SLC7A11. The iron concentration was changed with iron chelator DFO and iron supplementation FAC. The epithelial impairment was assessed by protein expression. To investigate the mechanism, si-MYB (a negative transcription factor of SLC7A11) and GPX4 inhibitor RSL3 were employed. Results: CDH1, OCLN, ZO-1 and GPX4 expression was decreased, while FTL expression was elevated in periodontitis tissues. Infected cells showed ferroptosis change of the mitochondria with higher level of lipid peroxidation, iron, FTL and lower level of GPX4, GSH, SLC7A11. FAC augmented ferroptosis and weakened epithelial junction, while DFO exhibited a counteractive effect. Silencing MYB rescued SLC7A11, GPX4 and epithelial junction proteins, which was hindered by RSL3. Conclusions: Our study demonstrated that P. gingivalis weakened the oral epithelial barrier by causing ferroptosis via inhibiting SLC7A11/GSH/GPX4 axis.

Artificial intelligence tools for optimising recruitment and retention in clinical trials: a scoping review protocol.

INTRODUCTION: In recent years, the influence of artificial intelligence technology on clinical trials has been steadily increasing. It has brought about significant improvements in the efficiency and cost reduction of clinical trials. The objective of this scoping review is to systematically map, describe and summarise the current utilisation of artificial intelligence in recruitment and retention process of clinical trials that has been reported in research. Additionally, the review aims to identify benefits and drawbacks, as well as barriers and facilitators associated with the application of artificial intelligence in optimising recruitment and retention in clinical trials. The findings of this review will provide insights and recommendations for future development of artificial intelligence in the context of clinical trials. METHODS AND ANALYSIS: The review of relevant literature will follow the methodological framework for scoping studies provided by the Joanna Briggs Institute. A comprehensive electronic search will be conducted using the search strategy developed by the authors. Leading medical and computer science databases such as PubMed, Embase, Scopus, IEEE Xplore and Web of Science Core Collection will be searched. The search will encompass analytical observational studies, descriptive observational studies, experimental and quasi-experimental studies published in all languages, without any time limitations, which use artificial intelligence tools in the recruitment and retention process of clinical trials. The review team will screen the identified studies and import them into a dedicated electronic library specifically created for this review. Data extraction will be performed using a data charting table. ETHICS AND DISSEMINATION: Secondary data will be attained in this scoping review; therefore, no ethical approval is required. The results of the final review will be published in a peer-reviewed journal. It is expected that results will inform future artificial intelligence and clinical trials research.

Autoimmune diseases and risk of non-Hodgkin lymphoma: A Mendelian randomisation study.

Objective: To examine whether genetically predicted susceptibility to ten autoimmune diseases (Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and type 1 diabetes) is associated with risk of non-Hodgkin lymphoma (NHL). Design: Two sample Mendelian randomization (MR) study. Setting: Genome wide association studies (GWASs) of ten autoimmune diseases, NHL, and four NHL subtypes (i.e., follicular lymphoma, mature T/natural killer-cell lymphomas, non-follicular lymphoma, and other and unspecified types of NHL). Analysis: We used data from the largest publicly available GWASs of European ancestry for each autoimmune disease, NHL, and NHL subtypes. For each autoimmune disease, we extracted single nucleotide polymorphisms (SNPs) strongly associated (P < 5×10-8) with that disease and that were independent of one another (R2 < 1×10-3) as genetic instruments. SNPs within the human leukocyte antigen region were not considered due to potential pleiotropy. Our primary MR analysis was the inverse-variance weighted analysis. Additionally, we conducted MR-Egger, weighted mode, and weighted median regression to address potential bias due to pleiotropy, and robust adjusted profile scores to address weak instrument bias. We carried out sensitivity analysis limited to the non-immune pathway for nominally significant findings. To account for multiple testing, we set the thresholds for statistical significance at P < 5×10-3. Participants: The number of cases and controls identified in the relevant GWASs were 437 and 3,325 for Behçet's disease, 4,918 and 5,684 for coeliac disease, 435 and 341,188 for dermatitis herpetiformis, 4,576 and 8,039 for lupus, 11,988 and 275,335 for psoriasis, 22,350 and 74,823 for rheumatoid arthritis, 3,597 and 337,121 for sarcoidosis, 2,735 and 332,115 for Sjögren's syndrome, 9,095 and 17,584 for systemic sclerosis, 18,942 and 501,638 for type 1 diabetes, 2,400 and 410,350 for NHL; and 296 to 2,340 cases and 271,463 controls for NHL subtypes. Exposures: Genetic variants predicting ten autoimmune diseases: Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and type 1 diabetes. Main outcome measures: Estimated associations between genetically predicted susceptibility to ten autoimmune diseases and the risk of NHL. Results: The variance of each autoimmune disease explained by the SNPs ranged from 0.3% to 3.1%. Negative associations between type 1 diabetes and sarcoidosis and the risk of NHL were observed (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.92 to 0.98, P = 5×10-3, and OR 0.92, 95% CI: 0.85 to 0.99, P = 2.8×10-2, respectively). These findings were supported by the sensitivity analyses accounting for potential pleiotropy and weak instrument bias. No significant associations were found between the other eight autoimmune diseases and NHL risk. Of the NHL subtypes, type 1 diabetes was most strongly associated with follicular lymphoma (OR 0.91, 95% CI: 0.86 to 0.96, P = 1×10-3), while sarcoidosis was most strongly associated with other and unspecified NHL (OR 0.86, 95% CI: 0.75 to 0.97, P = 1.8×10-2). Conclusions: These findings suggest that genetically predicted susceptibility to type 1 diabetes, and to some extent sarcoidosis, might reduce the risk of NHL. However, future studies with different datasets, approaches, and populations are warranted to further examine the potential associations between these autoimmune diseases and the risk of NHL.

Mediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes: A Mendelian Randomization Study.

Importance: Lower educational attainment is associated with increased risk of adverse pregnancy outcomes, but it is unclear which pathways mediate this association. Objective: To investigate the association between educational attainment and pregnancy outcomes and the proportion of this association that is mediated through modifiable cardiometabolic risk factors. Design, Setting, and Participants: In this 2-sample mendelian randomization (MR) cohort study, uncorrelated (R2 < 0.01) single-nucleotide variants (formerly single-nucleotide polymorphisms) associated with the exposure (P < 5 × 10-8) and mediators and genetic associations with the pregnancy outcomes from genome-wide association studies were extracted. All participants were of European ancestry and were largely from Finland, Iceland, the United Kingdom, or the US. The inverse variance-weighted method was used in the main analysis, and the weighted median, weighted mode, and MR Egger regression were used in sensitivity analyses. In mediation analyses, the direct effect of educational attainment estimated in multivariable MR was compared with the total effect estimated in the main univariable MR analysis. Data were extracted between December 1, 2022, and April 30, 2023. Exposure: Genetically estimated educational attainment. The mediators considered were genetically estimated type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure. Main Outcomes and Measures: Ectopic pregnancy, hyperemesis gravidarum, gestational diabetes, preeclampsia, preterm birth, and offspring birth weight. Results: The analyses included 3 037 499 individuals with data on educational attainment, and those included in studies on pregnancy outcomes ranged from 141 014 for ectopic pregnancy to 270 002 with data on offspring birth weight. Each SD increase in genetically estimated educational attainment (ie, 3.4 years) was associated with an increased birth weight of 42 (95% CI, 28-56) g and an odds ratio ranging from 0.53 (95% CI, 0.46-0.60) for ectopic pregnancy to 0.81 (95% CI, 0.71-0.93) for preeclampsia. The combined proportion of the association that was mediated by the 5 cardiometabolic risk factors ranged from -17% (95% CI, -46% to 26%) for hyperemesis gravidarum to 78% (95% CI, 10%-208%) for preeclampsia. Sensitivity analyses accounting for pleiotropy were consistent with the main analyses. Conclusions and Relevance: In this MR cohort study, intervening for type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure may lead to reductions in several adverse pregnancy outcomes associated with lower levels of education. Such public health interventions would serve to reduce health disparities attributable to social inequalities.

Overexpression of bond-forming active protein for efficient production of silk with structural changes and properties enhanced in silkworm.

Silkworm silk exhibits excellent mechanical properties, biocompatibility, and has potential applications in the biomedical sector. This study focused on enhancing the mechanical properties of Bombyx mori silk by overexpressing three bond-forming active proteins (BFAPs): AFP, HSP, and CRP in the silk glands of silkworms. Rheological tests confirmed increased viscoelasticity in the liquid fibroin stock solution of transgenic silkworms, and dynamic mechanical thermal analysis (DMTA) indicated that all three BFAPs participated in the interactions between fibroin molecular networks in transgenic silk. The mechanical property assay indicated that all three BFAPs improved the mechanical characteristics of transgenic silk, with AFP and HSP having the most significant effects. A synchrotron radiation Fourier transform infrared spectroscopy assay showed that all three BFAPs increased the ß-sheet content of transgenic silk. Synchrotron radiation wide-angle X-ray diffraction assay showed that all three BFAPs changed the crystallinity, crystal size, and orientation factor of the silk. AFP and HSP significantly improved the mechanical attributes of transgenic silk through increased crystallinity, refined crystal size, and a slight decrease in orientation. This study opens new possibilities for modifying silk and other fiber materials.

FAM201A encodes small protein NBASP to inhibit neuroblastoma progression via inactivating MAPK pathway mediated by FABP5.

Increasing evidence indicates that long non-coding RNA (lncRNA) is one of the most important RNA regulators in the pathogenesis of neuroblastoma (NB). Here, we found that FAM201A was low expressed in NB and a variety of gain and loss of function studies elucidated the anti-tumor effects of FAM201A on the regulation of proliferation, migration and invasion of NB cells. Intriguingly, we identified the ability of FAM201A to encode the tumor-suppressing protein, NBASP, which interacted with FABP5 and negatively regulated its expression. In vivo assays also revealed NBASP repressed NB growth via inactivating MAPK pathway mediated by FABP5. In conclusion, our findings demonstrated that NBASP encoded by FAM201A played a tumor-suppressor role in NB carcinogenesis via down-regulating FABP5 to inactivate the MAPK pathway. These results extended our understanding of the relationship of lncRNA-encoded functional peptides and plasticity of tumor progression.

Informed consent in cancer clinical drug trials in China: a narrative literature review of the past 20 years.

BACKGROUND: Although the number of cancer clinical drug trials is increasing rapidly in China, issues concerning informed consent in this research context are understudied. By performing a narrative literature review, we aim to describe the current situation and identify the most salient challenges affecting informed consent in cancer clinical drug trials among adult patients in China since 2000. METHODS: We searched Web of Science (WOS), PubMed, Scopus, EMBASE, the Cochrane Library databases, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database on Disc (CBMdisc), Chinese Scientific Journals Fulltext Database (CQVIP), and WANFANG Data to identify relevant publications since 2000. Data were extracted by three reviewers on six items pertaining to study type, theme, and challenges. RESULTS: We identified 37 unique manuscripts, from which 19 full texts were obtained and six were included in the review. All six studies were published in Chinese journals, and the publication years of the majority (five out of six) of the studies were 2015 or later. The authors of the six studies were all from clinical departments or ethical review committees at five hospitals in China. All of the included publications were descriptive studies. Publications reported challenges related to the following aspects of informed consent: information disclosure, patient understanding, voluntariness, authorization, and procedural steps. CONCLUSION: Based on our analysis of publications over the past two decades, there are currently frequent challenges related to various aspects of informed consent in cancer clinical drug trials in China. Furthermore, only a limited number of high-quality research studies on informed consent in cancer clinical drug trials in China are available to date. Efforts toward improvement of informed consent practice, in the form of guidelines or further regulations in China, should draw on both experience from other countries and high-quality local evidence.

Methylmalonic acid promotes colorectal cancer progression via activation of Wnt/ß-catenin pathway mediated epithelial-mesenchymal transition.

BACKGROUND: It has been manifested in several studies that age-related metabolic reprogramming is associated with tumor progression, in particular, colorectal cancer (CRC). Here we investigated the role of upregulated metabolites of the aged serum, including methylmalonic acid (MMA), phosphoenolpyruvate (PEP), and quinolinate (QA), in CRC. METHODS: Functional assays including CCK-8, EdU, colony formation and transwell experiments were used to ascertain which upregulated metabolite of elderly serum was related to tumor progression. RNA-seq analysis was conducted to explore the potential mechanisms of MMA-induced CRC progression. Subcutaneous tumorigenesis and metastatic tumor models were constructed to verify the function of MMA in vivo. RESULTS: Among three consistently increased metabolites of the aged sera, MMA was responsible for tumorigenesis and metastasis in CRC, according to functional assays. The promotion of Epithelial-mesenchymal transition (EMT) was observed in CRC cells treated with MMA, on the basis of protein expression of EMT markers. Moreover, combined with transcriptome sequencing, Wnt/ß-catenin signaling pathway was activated in CRC cells treated with MMA, which was verified by western blot and qPCR experiments. Furthermore, animal assays demonstrated the pro-proliferation and promotion of metastasis role of MMA in vivo. CONCLUSION: We have identified that age-dependent upregulation of MMA in serum promoted the progression of CRC via Wnt/ß-catenin signaling pathway mediated EMT. These collective findings provide valuable insights into the vital role of age-related metabolic reprogramming in CRC progression and propose a potential therapeutic target for elderly CRC.

Research Progress of Treatment Technology and Adsorption Materials for Removing Chromate in the Environment.

Cr is used extensively in industry, so the number of Cr (VI) hazards is increasing. The effective control and removal of Cr (VI) from the environment are becoming an increasing research priority. In order to provide a more comprehensive description of the research progress of chromate adsorption materials, this paper summarizes the articles describing chromate adsorption in the past five years. It summarizes the adsorption principles, adsorbent types, and adsorption effects to provide methods and ideas to solve the chromate pollution problem further. After research, it is found that many adsorbents reduce adsorption when there is too much charge in the water. Besides, to ensure adsorption efficiency, there are problems with the formability of some materials, which impact recycling.

MTM-HCC at Previous Liver Resection as a Predictor of Overall Survival in Salvage Liver Transplantation.

OBJECTIVES: Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. MATERIAL AND METHODS: A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. RESULTS: The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. CONCLUSIONS: Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.

Research Progress on Up-Conversion Fluorescence Probe for Detection of Perfluorooctanoic Acid in Water Treatment.

Perfluorooctanoic acid (PFOA) is a new type of organic pollutant in wastewater that is persistent, toxic, and accumulates in living organisms. The development of rapid and sensitive analytical methods to detect PFOA in environmental media is of great importance. Fluorescence detection has the advantages of high efficiency and low cost, in which fluorescent probes have excellent fluorescence properties, excellent bio-solubility, and remarkable photostability. It is necessary to review the fluorescence detection routes for PFOA. In addition, the up-conversion of fluorescent materials (UCNPs), as fluorescent materials to prepare fluorescent probes with, has significant advantages and also attracts the attention of researchers, however, reviews related to their application in detecting PFOA and comparing them with other routes are rare. Furthermore, there are many strategies to improve the performance of up-conversion fluorescent probes including SiO2 modification and amino modification. These strategies can enhance the detection effect of PFOA. Thus, this work reviews the types of fluorescence detection, the design, and synthesis of UCNPs, their recognition mechanism, properties, and their application progress. Moreover, the development trend and prospects of these detection probes are given.

Spatio-Temporal Evolution and Influencing Factors of Ecological Well-Being Performance from the Perspective of Strong Sustainability: A Case Study of the Three Gorges Reservoir Area, China.

The concept of strong sustainability suggests that natural capital is irreplaceable and emphasizes that human natural consumption cannot exceed the carrying capacity of the ecological environment. In the realistic context of tightening resource constraints and ecological degradation, how to explore the optimal economic and well-being output under certain ecological constraints has become an important topic in sustainability research. Ecological well-being performance (EWP) can comprehensively reflect the efficiency of natural resources and ecological inputs into the well-being level and has become an important tool for sustainable development research. Based on strong sustainability, this paper constructs an EWP evaluation index system. It decomposes EWP into two stages: ecological economy and economic well-being, which opens the "black box" of the ecological well-being conversion process. PCA-DEA, the network super-efficiency Epsilon-based measure (Network SEBM) model, and Geodetector are used to dynamically measure the EWP in the Three Gorges Reservoir Area (TGRA) from 2010 to 2020 and analyze its spatial and temporal characteristics and influencing factors. The results show that (1) temporally, the EWP in the TGRA shows an increasing trend from 2010 to 2020, but the overall level is low. Spatially, it shows a high pattern in the east and low in the west, and spatial differences are gradually decreasing; (2) ecological economic efficiency is significantly lower than economic well-being efficiency, and ecological economic efficiency is the main reason limiting the improvement in EWP in the TGRA. The ecological well-being situation of the TGRA is not optimistic; (3) there is an overall problem of excessive ecological input and insufficient per-capita GDP and well-being output in the TGRA, and decisions should be made according to local conditions; (4) the level of economic development has an EWP level that plays a dominant role and also has a greater relationship with the policy system, socioeconomic conditions, and natural environment.

Moral decision-making in pettism: The influence of animal type, pet ownership status, and social distance.

Speciesism prioritizes humans over animals and pets. Nevertheless, pet owners have a strong attachment bond with their pets, which makes their hierarchical view of pets less clear. Aiming to examine this issue, we present a dilemma involving animals and humans that allowed us to investigate whether animal type, social distance, and pet ownership status can affect moral decision-making related to pets. Save-willingness results showed that in the moral dilemmas of pets versus livestock versus wild animals (Studies 1a and 2a) and their own pets versus strangers (Studies 1b and 2b), pet owners prioritize pets whereas non-owners prioritize pets (Studies 1a and 2a) and strangers (Studies 1b and 2b). Pet owners prefer to save pets more than do non-owners (Study 1a), and this effect was only observed in females (Study 2a). Save-decision results showed that in the moral dilemmas of pets versus livestock versus wild animals (Study 2a), pet owners prioritize pets whereas in the dilemmas of pets versus strangers (Study 2b), pet owners prioritize strangers. The same result was found in non-owners. Pet owners prefer more than do non-owners to save pets (Study 2). Overall, the separation of save-willingness and save-decision results revealed that pet owners show special speciesism (i.e., pettism).

Suicidal behavior, depression and loneliness among college students: the role of school belonging.

Suicide among college students, as a subgroup of young people, has received increasing attention in recent years. Exploring the determination of protective and risk factors related to suicide is imperative to understanding the reason for committing suicide and how to take action. We examined loneliness and school belonging as predictors of suicide risk (viz., suicidal behavior and depression) in college students in China by a cross-sectional study. In total, 393 college students participated in the study. The results of hierarchical regression analyses that controlled for age and sex indicated that school belonging buffers the negative effects of loneliness on suicidal behavior and depression. Evidence of a significant loneliness × school belonging interaction as a predictor of both suicidal behavior and depression was found. The present findings show that school belonging represents a positive psychological resource that should be considered in understanding suicide risk among college students in China. More attention should be given to improving the school belonging of college students.

Comparison of Clinical Study Results Reported in medRxiv Preprints vs Peer-reviewed Journal Articles.

Importance: Preprints have been widely adopted to enhance the timely dissemination of research across many scientific fields. Concerns remain that early, public access to preliminary medical research has the potential to propagate misleading or faulty research that has been conducted or interpreted in error. Objective: To evaluate the concordance among study characteristics, results, and interpretations described in preprints of clinical studies posted to medRxiv that are subsequently published in peer-reviewed journals (preprint-journal article pairs). Design, Setting, and Participants: This cross-sectional study assessed all preprints describing clinical studies that were initially posted to medRxiv in September 2020 and subsequently published in a peer-reviewed journal as of September 15, 2022. Main Outcomes and Measures: For preprint-journal article pairs describing clinical trials, observational studies, and meta-analyses that measured health-related outcomes, the sample size, primary end points, corresponding results, and overarching conclusions were abstracted and compared. Sample size and results from primary end points were considered concordant if they had exact numerical equivalence. Results: Among 1399 preprints first posted on medRxiv in September 2020, a total of 1077 (77.0%) had been published as of September 15, 2022, a median of 6 months (IQR, 3-8 months) after preprint posting. Of the 547 preprint-journal article pairs describing clinical trials, observational studies, or meta-analyses, 293 (53.6%) were related to COVID-19. Of the 535 pairs reporting sample sizes in both sources, 462 (86.4%) were concordant; 43 (58.9%) of the 73 pairs with discordant sample sizes had larger samples in the journal publication. There were 534 pairs (97.6%) with concordant and 13 pairs (2.4%) with discordant primary end points. Of the 535 pairs with numerical results for the primary end points, 434 (81.1%) had concordant primary end point results; 66 of the 101 discordant pairs (65.3%) had effect estimates that were in the same direction and were statistically consistent. Overall, 526 pairs (96.2%) had concordant study interpretations, including 82 of the 101 pairs (81.2%) with discordant primary end point results. Conclusions and Relevance: Most clinical studies posted as preprints on medRxiv and subsequently published in peer-reviewed journals had concordant study characteristics, results, and final interpretations. With more than three-fourths of preprints published in journals within 24 months, these results may suggest that many preprints report findings that are consistent with the final peer-reviewed publications.

Characteristics of Retracted Research Articles About COVID-19 vs Other Topics.

This cross-sectional study compares the author and journal characteristics of retracted articles on COVID-19 with retracted articles from other topics.

Characterization and corroboration of safety signals identified from the US Food and Drug Administration Adverse Event Reporting System, 2008-19: cross sectional study.

OBJECTIVE: To characterize potential drug safety signals identified from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), from 2008 to 2019, to determine how often these signals resulted in regulatory action by the FDA and whether these actions were corroborated by published research findings or public assessments by the Sentinel Initiative. DESIGN: Cross sectional study. SETTING: USA. POPULATION: Safety signals identified from the FAERS and publicly reported by the FDA between 2008 and 2019; and review of the relevant literature published before and after safety signals were reported in 2014-15. Literature searches were performed in November 2019, Sentinel Initiative assessments were searched in December 2021, and data analysis was finalized in December 2021. MAIN OUTCOME MEASURES: Safety signals and resulting regulatory actions; number and characteristics of published studies, including corroboration of regulatory action as evidenced by significant associations (or no associations) between the drug related to the signal and the adverse event. RESULTS: From 2008 to 2019, 603 potential safety signals identified from the FAERS were reported by the FDA (median 48 annually, interquartile range 41-61), of which 413 (68.5%) were resolved as of December 2021 (372 of 399 (93.2%) signals ≥3 years old were resolved). Among the resolved safety signals, 91 (22.0%) led to no regulatory action and 322 (78.0%) resulted in regulatory action, including 319 (77.2%) changes to drug labeling and 59 (14.3%) drug safety communications or other public communications from the FDA. For a subset of 82 potential safety signals reported in 2014-15, a literature search identified 1712 relevant publications; 1201 (70.2%) were case reports or case series. Among these 82 safety signals, 76 (92.7%) were resolved, of which relevant published research was identified for 57 (75.0%) signals and relevant Sentinel Initiative assessments for four (5.3%) signals. Regulatory actions by the FDA were corroborated by at least one relevant published research study for 17 of the 57 (29.8%) resolved safety signals; none of the relevant Sentinel Initiative assessments corroborated FDA regulatory action. CONCLUSIONS: Most potential safety signals identified from the FAERS led to regulatory action by the FDA. Only a third of regulatory actions were corroborated by published research, however, and none by public assessments from the Sentinel Initiative. These findings suggest that either the FDA is taking regulatory actions based on evidence not made publicly available or more comprehensive safety evaluations might be needed when potential safety signals are identified.

The Association between Systemic Immune-Inflammation Index and All-Cause Mortality in Acute Ischemic Stroke Patients: Analysis from the MIMIC-IV Database.

Purpose: Acute ischemic stroke (AIS) is a devastating disease and remains the leading cause of death and disability. This retrospective study aims to investigate associations between systemic immune-inflammation index (SII) and all-cause mortality in patients with AIS. Patients and Methods. We used the data from Medical Information Mart for Intensive Care IV. A total of 1,181 patients with acute ischemic stroke (AIS) were included. Systemic immune-inflammation index (SII) was calculated as platelet count (/L) × neutrophil count (/L)/lymphocyte count (/L). The main outcomes were 30-day all-cause mortality. The association between SII with mortality was evaluated using the Cox proportional hazards regression model. Results: After adjusting for potential covariates, the highest quartiles of SII versus the lowest quartiles of SII, the HR was 2.74 (CI 1.79-4.19, P < 0.001). Log-transformed SII was significantly associated with 30-day all-cause mortality (HR 2.44; CI 1.72-3.46, P < 0.001). Furthermore, we found that there is a nearly linear relationship (P=0.265) between logarithmic transformed SII with all-cause mortality. Conclusion: Elevated SII of patients with acute ischemic stroke increased the risk of 30-day all-cause mortality. SII may serve as a useful marker to elucidate the role of thrombocytosis, inflammation, and immunity interaction in the development of AIS.

Serum lutein is a promising biomarker for type 2 diabetes mellitus and diabetic kidney disease in the elderly.

OBJECTIVE: To investigate the relationship between serum lutein and type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD) in elderly individuals. METHODS: A total of 60 T2DM patients over 60 years were subgrouped into a DKD group and a non-DKD group according to their urinary microalbumin-to-creatinine ratio (UACR), while 30 age-matched non-T2DM patients were recruited in the control group. Baseline characteristics, laboratory examination results, and serum lutein levels were compared, and their correlations were analyzed. Receiver operating characteristic (ROC) curves were plotted to identify the diagnostic potential of lutein in T2DM and DKD. RESULTS: The lutein level in the T2DM group was significantly lower than that in the control group and was also significantly lower in the DKD group than in the non-DKD group (p < 0.001). Lutein levels were negatively correlated with body mass index, glycosylated hemoglobin, fasting blood glucose, triglyceride, and UACR and positively correlated with high-density lipoprotein cholesterol (p < 0.05). T2DM patients were divided into four groups according to the quartile of their lutein level. The proportion of T2DM and DKD gradually decreased with increasing lutein levels (p < 0.001). The area under the ROC curve of serum lutein in diagnosing T2DM and DKD was 0.880 and 0.779, respectively, with corresponding cut-off values of 0.433 µmol/L and 0.197 µmol/L (p < 0.001). CONCLUSION: The serum level of lutein is negatively correlated with the incidence of T2DM and DKD in the elderly and can serve as a diagnostic marker for T2DM and DKD.