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1.
Stem Cell Res ; 79: 103501, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39029293

ABSTRACT

Apolipoprotein E (APOE)is the gene with greatest genetic risk for Alzheimer's disease (AD). We successfully established a human induced pluripotent stem cell(iPSC) line from a woman mutated by APOE gene. The cell line was isolated from this woman's peripheral blood mononuclear cells using a non-integrated Sendai virus, which retained the original genotype, showed a normal karyotype, highly expressed pluripotent markers and could differentiate into three germ layers.

2.
BMJ Open ; 14(7): e082404, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39002963

ABSTRACT

INTRODUCTION: The efficacy of multitarget neuroprotective drug DL-3-n-butylphthalide (NBP) in improving cognitive function has been confirmed in patients with vascular cognitive impairment without dementia. However, its efficacy in patients with symptomatic predementia phase of Alzheimer's disease remains uncertain. This study aims to evaluate the efficacy and safety of NBP in improving cognitive function in patients with mild cognitive impairment (MCI) through a clinical randomised controlled trail. METHODS AND ANALYSIS: This study is a 12-month, randomised, double-blind, placebo-controlled, multicentric trial, involving 270 patients with MCI. Subjects are randomly assigned to receive either NBP soft capsule (200 mg, three times per day) or placebo with an allocation ratio of 1:1. The efficacy and safety of NBP are assessed by comparing the results of neuropsychological, neuroimaging and laboratory tests between the two groups. The primary endpoint is the change in Alzheimer's Disease Assessment Scale-Cognitive Subscale after 12 months. All patients will be monitored for adverse events. ETHICS AND DISSEMINATION: This study involving human participants has been reviewed and approved by Ethics Committee of Xuan Wu Hospital (No.2017058). The participants provide their written informed consent to participate in this study. Results will be published in peer-reviewed medical journals and disseminated to healthcare professionals at local and international conferences. PROTOCOL VERSION: V 3.0, 3 September 2022. TRIAL REGISTRATION NUMBER: ChiCTR1800018362.


Subject(s)
Benzofurans , Cognitive Dysfunction , Neuroprotective Agents , Humans , Benzofurans/therapeutic use , Benzofurans/adverse effects , Cognitive Dysfunction/drug therapy , Double-Blind Method , Male , Aged , Female , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/adverse effects , Middle Aged , Treatment Outcome , Randomized Controlled Trials as Topic , Neuropsychological Tests , Cognition/drug effects , Multicenter Studies as Topic
3.
Front Aging Neurosci ; 16: 1423139, 2024.
Article in English | MEDLINE | ID: mdl-39076205

ABSTRACT

Background: Alzheimer's disease (AD) is the predominant cause of dementia on a global scale, significantly impacting the health of the elderly population. The pathogenesis of AD is closely linked to neuroinflammation. The present study employs a bibliometric analysis to examine research pertaining to neuroinflammation and AD within the last decade, with the objective of providing a comprehensive overview of the current research profile, hotspots and trends. Methods: This research conducted a comprehensive review of publications within the Science Citation Index Expanded of the Web of Science Core Collection Database spanning the years 2014 to 2024. Bibliometric analyses were performed using VOSviewer (version 1.6.19) and CiteSpace (version 6.3.R1) software to visualize data on countries, institutions, authors, journals, keywords, and references. Results: A total of 3,833 publications on neuroinflammation and AD were included from January 2014 to January 2024. Publications were mainly from the United States and China. Zetterberg, Henrik emerged as the author with the highest publication output, while Edison, Paul was identified as the most cited author. The most productive journal was Journal of Alzheimers Disease, and the most co-cited was Journal of Neuroinflammation. Research hotspot focused on microglia, mouse models, oxidative stress, and amyloid-beta through keyword analysis. Additionally, keywords such as blood-brain barrier and tau protein exhibited prolonged citation bursts from 2022 to 2024. Conclusion: This study provides a comprehensive review of the last 10 years of research on neuroinflammation and AD, including the number and impact of research findings, research hotspots, and future trends. The quantity of publications in this field is increasing, mainly in the United States and China, and there is a need to further strengthen close cooperation with different countries and institutions worldwide. Presently, research hotspots are primarily concentrated on microglia, with a focus on inhibiting their pro-inflammatory responses and promoting their anti-inflammatory functions as a potential direction for future investigations.

4.
Heliyon ; 10(13): e34194, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39071671

ABSTRACT

Objective: This research sought to explore the association between the triglyceride-glucose (TyG) index and the risk of sarcopenia in patients with chronic inflammatory airway disease (CIAD). Methods: Data were obtained from the National Health and Nutrition Examination Survey 2011-2018. Grouping was performed using TyG index tertiles and multiple logistic regression was employed to assess the correlation between TyG levels and the risk of sarcopenia. The Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the prognostic value of the TyG index for sarcopenia. Linear regression analysis was utilized to elucidate the direct relationship between TyG index and sarcopenia. Additionally, the curve between the TyG and sarcopenia indices was examined using a generalized additive model. Results: The study included 981 individuals diagnosed with CIAD. After adjusting for potential confounders, a significant positive correlation was observed between TyG and sarcopenia (OR = 1.70, 95 % CI: 1.20-2.39, P = 0.002). Trend analysis using the chi-square test revealed an increase in sarcopenia prevalence concomitant with higher TyG levels (P < 0.05). Furthermore, linear regression analysis revealed a notable inverse linear association between the TyG and sarcopenia indices (ß = -0.03; 95 % CI: -0.07-0.01; P = 0.020). The ROC curves corroborated the robust predictive capacity of TyG for sarcopenia among patients with CIAD, with an AUC of 0.685 (95 % CI: 0.636-0.735, P < 0.001). Conclusion: Our research indicates a positive association between TyG and sarcopenia in CIAD patients. The TyG index may serve as a reliable marker for predicting sarcopenia risk in CIAD patients.

5.
J Colloid Interface Sci ; 674: 326-335, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38936089

ABSTRACT

The rational design of catalysts with atomic dispersion and a deep understanding of the catalytic mechanism is crucial for achieving high performance in CO2 reduction reaction (CO2RR). Herein, we present an atomically dispersed electrocatalyst with single Cu atom and atomic Ni clusters supported on N-doped mesoporous hollow carbon sphere (CuSANiAC/NMHCS) for highly efficient CO2RR. CuSANiAC/NMHCS demonstrates a remarkable CO Faradaic efficiency (FECO) exceeding 90% across a potential range of -0.6 to -1.2 V vs. reversible hydrogen electrode (RHE) and achieves its peak FECO of 98% at -0.9 V vs. RHE. Theoretical studies reveal that the electron redistribution and modulated electronic structure-notably the positive shift in d-band center of Ni 3d orbital-resulting from the combination of single Cu atom and atomic Ni clusters markedly enhance the CO2 adsorption, facilitate the formation of *COOH intermediate, and thus promote the CO production activity. This study offers fresh perspectives on fabricating atomically dispersed catalysts with superior CO2RR performance.

6.
Small ; : e2402867, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38850185

ABSTRACT

A considerable challenge in CO2 reduction reaction (CO2RR) to produce high-value-added chemicals comes from the adsorption and activation of CO2 to form intermediates. Herein, an amino-induced spillover strategy aimed at significantly enhancing the CO2 adsorption and activation capabilities of CdS supported on N-doped mesoporous hollow carbon sphere (NH2-CdS/NMHCS) for highly efficient CO2RR is presented. The prepared NH2-CdS/NMHCS exhibits a high CO Faradaic efficiency (FECO) exceeding 90% from -0.8 to -1.1 V versus reversible hydrogen electrode (RHE) with the highest FECO of 95% at -0.9 V versus RHE in H cell. Additional experimental and theoretical investigations demonstrate that the alkaline -NH2 group functions as a potent trapping site, effectively adsorbing the acidic CO2, and subsequently triggering CO2 spillover to CdS. The amino modification-induced CO2 spillover, combined with electron redistribution between CdS and NMHCS, not only readily achieves the spontaneous activation of CO2 to *COOH but also greatly reduces the energy required for the conversion of *COOH to *CO intermediate, thus endowing NH2-CdS/NMHCS with significantly improved reaction kinetics and reduced overpotential for CO2-to-CO conversion. It is believed that this research can provide valuable insights into the development of electrocatalysts with superior CO2 adsorption and activation capabilities for CO2RR application.

7.
Eur J Pediatr ; 183(5): 2353-2363, 2024 May.
Article in English | MEDLINE | ID: mdl-38429545

ABSTRACT

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/mortality , COVID-19/complications , COVID-19/diagnosis , Male , Female , Child , Prognosis , Risk Factors , Child, Preschool , Infant , Adolescent , Nervous System Diseases/etiology , Nervous System Diseases/virology , Hospitalization/statistics & numerical data , Infant, Newborn , China/epidemiology , Child, Hospitalized/statistics & numerical data
8.
Stem Cell Res ; 77: 103398, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38552354

ABSTRACT

Genetic polymorphism of apolipoprotein E (APOE) confers differential susceptibility to Alzheimer's disease (AD), and APOE ɛ4 variants is the most powerful risk factor for this disease. Here, we report the generation of a human induced pluripotent stem cell (iPSC) line carrying the APOE ɛ4/ɛ4 genotype from peripheral blood mononuclear cells (PBMCs) isolated from a male with a family history of AD utilizing non-integrative Sendai virus vector. The iPSC maintains their original genotype, highly express endogenous pluripotency markers, displays a normal karyotype, and retains the ability to differentiate into cells representative of the three germ layers.


Subject(s)
Apolipoproteins E , Induced Pluripotent Stem Cells , Humans , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/cytology , Male , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Mutation , Cell Line , Cell Differentiation , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/cytology
9.
J Med Virol ; 96(2): e29447, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38305064

ABSTRACT

With the emergence of the Omicron variant, the number of pediatric Coronavirus Disease 2019 (COVID-19) cases requiring hospitalization and developing severe or critical illness has significantly increased. Machine learning and multivariate logistic regression analysis were used to predict risk factors and develop prognostic models for severe COVID-19 in hospitalized children with the Omicron variant in this study. Of the 544 hospitalized children including 243 and 301 in the mild and severe groups, respectively. Fever (92.3%) was the most common symptom, followed by cough (79.4%), convulsions (36.8%), and vomiting (23.2%). The multivariate logistic regression analysis showed that age (1-3 years old, odds ratio (OR): 3.193, 95% confidence interval (CI): 1.778-5.733], comorbidity (OR: 1.993, 95% CI:1.154-3.443), cough (OR: 0.409, 95% CI:0.236-0.709), and baseline neutrophil-to-lymphocyte ratio (OR: 1.108, 95% CI: 1.023-1.200), lactate dehydrogenase (OR: 1.993, 95% CI: 1.154-3.443), blood urea nitrogen (OR: 1.002, 95% CI: 1.000-1.003) and total bilirubin (OR: 1.178, 95% CI: 1.005-3.381) were independent risk factors for severe COVID-19. The area under the curve (AUC) of the prediction models constructed by multivariate logistic regression analysis and machine learning (RandomForest + TomekLinks) were 0.7770 and 0.8590, respectively. The top 10 most important variables of random forest variables were selected to build a prediction model, with an AUC of 0.8210. Compared with multivariate logistic regression, machine learning models could more accurately predict severe COVID-19 in children with Omicron variant infection.


Subject(s)
COVID-19 , Child, Hospitalized , Humans , Child , Infant , Child, Preschool , COVID-19/diagnosis , Logistic Models , SARS-CoV-2 , Cough , Machine Learning , Retrospective Studies
10.
Pharmaceuticals (Basel) ; 17(2)2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38399394

ABSTRACT

Early stage chemical development presents numerous challenges, and achieving a functional balance is a major hurdle, with many early compounds not meeting the clinical requirements for advancement benchmarks due to issues like poor oral bioavailability. There is a need to develop strategies for achieving the desired systemic concentration for these compounds. This will enable further evaluation of the biological response upon a compound-target interaction, providing deeper insight into the postulated biological pathways. Our study elucidates alternative drug delivery paradigms by comparing formulation strategies across oral (PO), intraperitoneal (IP), subcutaneous (SC), and intravenous (IV) routes. While each modality boasts its own set of merits and constraints, it is the drug's formulation that crucially influences its pharmacokinetic (PK) trajectory and the maintenance of its therapeutic levels. Our examination of model compounds G7883 and G6893 highlighted their distinct physio-chemical attributes. By harnessing varied formulation methods, we sought to fine-tune their PK profiles. PK studies showcased G7883's extended half-life using an SC oil formulation, resulting in a 4.5-fold and 2.5-fold enhancement compared with the IP and PO routes, respectively. In contrast, with G6893, we achieved a prolonged systemic coverage time above the desired target concentration through a different approach using an IV infusion pump. These outcomes underscore the need for tailored formulation strategies, which are dictated by the compound's innate properties, to reach the optimal in vivo systemic concentrations. Prioritizing formulation and delivery optimization early on is pivotal for effective systemic uptake, thereby facilitating a deeper understanding of biological pathways and expediting the overall clinical drug development timeline.

11.
Toxicol Appl Pharmacol ; 475: 116627, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37453479

ABSTRACT

SMARCA2 and SMARCA4 are the ATPases of the SWI/SNF chromatin remodeling complex, which play a significant role in regulating transcriptional activity and DNA repair in cells. SMARCA2 has become an appealing synthetic-lethal, therapeutic target in oncology, as mutational loss of SMARCA4 in many cancers leads to a functional dependency on residual SMARCA2 activity. Thus, for therapeutic development, an important step is understanding any potential safety target-associated liabilities of SMARCA2 inhibition. To best mimic a SMARCA2 therapeutic, a tamoxifen-inducible (TAMi) conditional knockout (cKO) rat was developed using CRISPR technology to understand the safety profile of Smarca2 genetic ablation in a model system that avoids potential juvenile and developmental phenotypes. As the rat is the prototypical rodent species utilized in toxicology studies, a comprehensive toxicological and pathological assessment was conducted in both heterozygote and homozygous knockout rats at timepoints up to 28 days, alongside relevant corresponding controls. To our knowledge, this represents the first TAMi cKO rat model utilized for safety assessment evaluations. No significant target-associated phenotypes were observed when Smarca2 was ablated in mature (11- to 15-week-old) rats; however subsequent induction of SMARCA4 was evident that could indicate potential compensatory activity. Similar to mouse models, rat CreERT2-transgene and TAMi toxicities were characterized to avoid confounding study interpretation. In summary, a lack of significant safety findings in Smarca2 cKO rats highlights the potential for therapeutics targeting selective SMARCA2 ATPase activity; such therapies are predicted to be tolerated in patients without eliciting significant on-target toxicities.


Subject(s)
Neoplasms , Tamoxifen , Mice , Rats , Animals , Tamoxifen/toxicity , Adenosine Triphosphatases , Mutation
12.
J Transl Med ; 21(1): 393, 2023 06 17.
Article in English | MEDLINE | ID: mdl-37330547

ABSTRACT

OBJECTIVE: Sarcopenia has been recognized as a third category of complications in people with diabetes. However, few studies focus on the reduction of skeletal muscle mass in young people with diabetes. The aim of this study was to investigate risk factors of pre-sarcopenia in young patients with diabetes and establish a practical tool to diagnose pre-sarcopenia in those people. METHODS: Patients (n = 1246) enrolled from the National Health and Nutrition Examination Survey (NHANES) cycle year of 2011 to 2018 were randomly divided into the training set and validation set. The all-subsets regression analysis was used to select the risk factors of pre-sarcopenia. A nomogram model for the prediction of pre-sarcopenia in the diabetic population was established based on the risk factors. The model was evaluated by the area under the receiver operating characteristic curve for discrimination, calibration curves for calibration, and decision curve analysis curves for clinical utility. RESULTS: In this study, gender, height, and waist circumference were elected as predictive factors for pre-sarcopenia. The nomogram model presented excellent discrimination in training and validation sets with areas under the curve of 0.907 and 0.912, respectively. The calibration curve illustrated excellent calibration, and the decision curve analysis showed a wide range of good clinical utility. CONCLUSIONS: This study develops a novel nomogram that integrates gender, height, and waist circumference and can be used to easily predict pre-sarcopenia in diabetics. The novel screen tool is accurate, specific, and low-cost, highlighting its potential value in clinical application.


Subject(s)
Diabetes Mellitus , Sarcopenia , Humans , Adolescent , Nutrition Surveys , Sarcopenia/complications , Sarcopenia/diagnosis , Sarcopenia/epidemiology , Diabetes Mellitus/epidemiology , Risk Factors , Calibration , Retrospective Studies
13.
Stem Cell Res ; 71: 103149, 2023 09.
Article in English | MEDLINE | ID: mdl-37356183

ABSTRACT

The ß-amyloid precursor protein (APP) is a crucial pathogenic gene linked to Alzheimer's disease (AD). A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) isolated from a female with APP gene mutation utilizing non-integrative Sendai virus. The iPSC line exhibits high expression of pluripotency markers, retains the APP mutation, displays a normal karyotype, and has the ability to differentiate into normal teratoma tissue. This iPSC line represents a valuable cell model for investigating the pathological mechanisms and therapeutic strategies of AD.


Subject(s)
Alzheimer Disease , Induced Pluripotent Stem Cells , Humans , Female , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Induced Pluripotent Stem Cells/metabolism , Leukocytes, Mononuclear/metabolism , Alzheimer Disease/pathology , Mutation/genetics , Cell Differentiation
14.
Heliyon ; 9(3): e14143, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36950593

ABSTRACT

Epithelial-mesenchymal transition (EMT) is a biological process that transforms epithelial cells into a mesenchymal phenotype, conferring cell migration and invasion capabilities. EMT is involved in the progression and metastasis of colorectal cancer (CRC). Recently, emerging evidence has shown dysregulation of non-coding RNA (ncRNA) was linked to EMT. ncRNAs, including long non-coding RNA (lncRNA), regulate the transcription of downstream target genes (mRNA) through interaction with microRNAs (miRNAs); these are termed competitive endogenous RNA (ceRNA) networks. CeRNA dysregulation-induced EMT, which is linked to the progression and prognosis of CRC, has attracted wide attention. However, understanding the role of the regulation of the ceRNA network in the EMT of CRC remains limited. We discuss the molecular functions of lncRNA, the ceRNA networks related to miRNAs and mRNAs in EMT, as well as EMT transcription factors, such as the zinc finger E-box binding homeobox 1/2 (ZEB1/2), SNAIL, SLUG, and TWIST1/2. In addition, miRNAs and lncRNAs that directly target genes, thereby initiating different signaling pathways to promote EMT in CRC, were summarized. Clarifying the role of these molecules in EMT is critical for understanding molecular mechanisms and exploring the potential therapeutic targets of CRC.

15.
Int Arch Allergy Immunol ; 184(5): 447-459, 2023.
Article in English | MEDLINE | ID: mdl-36657406

ABSTRACT

INTRODUCTION: Influenza A virus (IAV) infection causes severe lung inflammation and injury, particularly in children. Sirtuin3 (Sirt3) was confirmed to be effective in protecting the lung against injury. This study aims to explore the function and mechanism of Sirt3 on influenza development in children. METHODS: The Sirt3 level in serum samples from IAV-infected children and lung epithelial cells were detected using RT-qPCR, ELISA, and Western blot assays. Cell viability and apoptosis were determined by MTT and flow cytometry assays. Virus titration was conducted by determining TCID50. Cell inflammatory response was detected by a battery of inflammatory cytokines. The contents of ROS and ATP, mitochondrial membrane potential level, and oxygen-consumption rate were examined to reflect on oxidative stress and mitochondrial dysfunction. The activity of poly (ADP-ribose) polymerase 1 (PARP-1) was measured by colorimetry. RESULTS: Sirt3 was downregulated in IAV-infected children's serum samples and BEAS-2B cells. Overexpression of Sirt3 alleviated IAV replication and IAV-induced inflammatory injury, oxidative stress, and mitochondrial dysfunction in lung epithelial cells. Moreover, upregulation of Sirt3 deacetylated SOD2 and PARP-1 and inhibited the PARP-1 activity. Notably, the Sirt3 inhibitor (3-TYP) and PARP-1 activity agonist (nicotinamide) reversed the effects of Sirt3 overexpression on IAV replication and IAV-induced injury. CONCLUSION: Overexpression of Sirt3 attenuated IAV-evoked inflammatory injury and mitochondrial oxidative stress through the inhibition of PARP-1 activity in lung epithelial cells.


Subject(s)
Influenza A virus , Influenza, Human , Sirtuin 3 , Child , Humans , Epithelial Cells/metabolism , Inflammation/metabolism , Influenza A virus/metabolism , Lung/metabolism , Oxidative Stress , Sirtuin 3/genetics , Sirtuin 3/metabolism , Sirtuin 3/pharmacology , Influenza, Human/immunology , Influenza, Human/metabolism , Poly (ADP-Ribose) Polymerase-1/metabolism
16.
J Med Virol ; 95(1): e28339, 2023 01.
Article in English | MEDLINE | ID: mdl-36418181

ABSTRACT

The clinical features and factors associated with disease severity in children with hemorrhagic fever with renal syndrome (HFRS) have not been well characterized. This study analyzed the clinical and laboratory factors associated with disease severity in children with HFRS caused by Hantaan virus. Data in pediatric patients with HFRS were retrospectively collected from Xi'an Children's Hospital over a 9-year period. Independent factors associated with disease severity were identified. Nomogram predicting disease severity was constructed based on variables filtered by feature selection. In total, 206 children with HFRS were studied. Fever, digestive tract symptoms, headache, backache, bleeding, and renal injury signs were the common symptoms. Elevated white blood cell, reduced platelet, hematuria, proteinuria, coagulation abnormalities, increased blood urea nitrogen (BUN) and procalcitonin (PCT), decreased estimated glomerular filtration rate and low serum Na+ , Cl- , and Ca2+ were the common laboratory findings. In the 206 patients, 21 patients had critical type disease and 4 patients (1.9%) died. Hydrothorax, hypotension and cerebral edema/cerebral herniation at hospital admission were independent clinical characteristics, and neutrophil %, prothrombin activity, PCT, BUN, and Ca2+ at hospital admission were independent laboratory factors associated with critical disease. Feature selection identified BUN, PCT and prothrombin time as independent factors related to critical disease. A nomogram integrating BUN and PCT at admission was constructed and calibration showed high accuracy for the probability prediction of critical disease. In conclusion, this study characterized the clinical and laboratory features and constructed a nomogram predicting disease severity in pediatric HFRS, providing references for disease severity evaluation in managing children HFRS.


Subject(s)
Hantaan virus , Hemorrhagic Fever with Renal Syndrome , Humans , Child , Hemorrhagic Fever with Renal Syndrome/complications , Hemorrhagic Fever with Renal Syndrome/diagnosis , Retrospective Studies , Patient Acuity , Severity of Illness Index
18.
Environ Toxicol ; 37(7): 1618-1628, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35243748

ABSTRACT

It's known that APAP overdose often leads to hepatotoxicity and nephrotoxicity. In the present study, we investigated the preventative effect of Tan IIA on APAP-induced nephrotoxicity. Mice were orally administrated with Tan IIA (10 or 30 mg/kg/day) for 1 week and subsequently gavaged with 200 mg/kg of APAP. Tan IIA reduced APAP-induced nephrotoxicity as evidenced by histopathological evaluation and serum creatinine levels. Tan IIA pretreatment promoted the efflux of the toxic intermediate metabolite N-acetyl-p-benzoquinone imine (NAPQI), thus reduced its injury to mouse kidney. After Tan IIA pretreatment, a remarkable increase in mRNA and protein expression of Nrf2 and its target genes Mrp2 and Mrp4 was observed in Nrf2+/+ mice kidneys, however, no obvious change of Mrp2 and Mrp4 mRNA and protein expression was detected in Nrf2-/- mice kidneys. HK-2 cells were used for exploring the roles of Tan IIA in the Nrf2-MRPs pathway in vitro. Consistently, Tan IIA up-regulated the Nrf2-MRPs pathway and promoted the nuclear Nrf2 accumulation in HK-2 cells. Collectively, our findings suggested that Tan IIA facilitated the clearance of toxic intermediate metabolite NAPQI from the kidney through upregulation of the Nrf2-MRP2/4 pathway, thereby, performing preventive effects against APAP-induced nephrotoxicity.


Subject(s)
Abietanes , Acetaminophen , Kidney Diseases , Animals , Mice , Abietanes/pharmacology , Acetaminophen/pharmacology , Acetaminophen/toxicity , Kidney Diseases/chemically induced , Kidney Diseases/metabolism , Kidney Diseases/prevention & control , Mice, Inbred C57BL , Multidrug Resistance-Associated Protein 2/metabolism , Multidrug Resistance-Associated Proteins/genetics , Multidrug Resistance-Associated Proteins/metabolism , Multidrug Resistance-Associated Proteins/pharmacology , NF-E2-Related Factor 2/metabolism , RNA, Messenger/metabolism , Signal Transduction/drug effects
19.
J Hazard Mater ; 427: 128124, 2022 04 05.
Article in English | MEDLINE | ID: mdl-34973575

ABSTRACT

The addition of barium-based additives is one of the main methods used to suppress smoke emissions in non-road diesel engines. Herein, a commercial barium-based additive was added to diesel fuel at the manufacturer's recommended concentration and used in a non-road four-cylinder supercharged diesel engine, without an after-treatment system, in bench experiments. Regulated emissions of the diesel engine were measured, volatile organic compounds (VOCs) and particulate matter (PM) were sampled. The carbonaceous fraction, water-soluble ions and inorganic elements in the PM were analyzed. Results indicated that the additive effectively reduced carbon monoxide (CO), hydrocarbon (HC) and smoke emissions from the engine. A 71% reduction in smoke was observed at the rated working condition, which was the maximum reduction of the three tested conditions. The additive produced a 36% reduction of VOCs at the rated working condition. The proportion of high carbon number hydrocarbons in the VOCs increased while the atmospheric reactivity of the VOCs decreased. The additive suppressed the concentration of organic carbon (OC) and elemental carbon (EC) emissions with a maximum reduction (40%) of total carbon achieved under the rated working condition. After the application of the additive, the concentration of water-soluble ions (Cl-, SO42-, NO3-, Na+, K+, Ca2+, NH4+) and elements (Fe, Mn, S, Ca, Ba) in the PM increased. A trend of increasing Barium content in the PM matched a similar trend of decreasing smoke.


Subject(s)
Air Pollutants , Vehicle Emissions , Air Pollutants/analysis , Barium , Gases , Gasoline/analysis , Particulate Matter/analysis , Vehicle Emissions/analysis
20.
Front Nutr ; 9: 1051351, 2022.
Article in English | MEDLINE | ID: mdl-36606230

ABSTRACT

Background: Sunburn is a common problem for outdoor workers and casual outdoor walkers. Carotenoids are important elements in normal function of skin tissue and skin metabolism and are critical in the development of some cancers. However, the possible relationships between sunburn sensitivity, carotenoids and the risk of cancers remain unknown. Objectives: To explore the associations of serum carotenoids with sunburn severity and the risk of cancers. Methods: A cross-sectional study from the National Health and Nutrition Examination Survey from 1999 to 2018 were conducted. The relationship between sunburn and serum carotenoids, cancers were investigated by unconditional or ordinal logistic regression. Mediation analysis was used to explore the effect of carotenoids on the relationship between sunburn and cancers. Results: A total of 25,440 US adults from 1999 to 2018 were enrolled in this study. There were significant differences in sex, race and natural hair color between the sunburn and non-sunburn people. The severity of sunburn was significantly associated with serum trans-ß-carotene, cis-ß-carotene, combined lutein, and vitamin A. The odds ratios of severe reactions were 5.065 (95% CI: 2.266-11.318) in melanoma patients, 5.776 (95% CI: 3.362-9.922) in non-melanoma patients, and 1.880 (95% CI: 1.484-2.380) in non-skin cancers patients. Additionally, serum carotenoids were partially attributable to the effect of sunburn on skin and non-skin cancers. Conclusion: Sunburn severity was associated with cancers, and severer sunburn was related with higher risk of cancers. Serum carotenoids were also associated with sunburn severity. Moreover, the relationship between sunburn and cancers was mediated by some serum carotenoids.

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