Disease-related Research Research Articles

Recent advances in brain organoids: a comprehensive review of the last eight years

Organoids are three-dimensional cellular structures grown in vitro that can self-organize and differentiate into cell types with organ-specific functions, closely mimicking the biological properties of tissues and organs in vivo. Brain organoids, which differentiate into structures resembling brain function, serve as valuable models for medical research, including disease microenvironment simulation, brain mechanism exploration, and drug evaluation. In this review, we analyzed 808 articles retrieved from PubMed, CNKI, and Wanfang databases using the keyword "brain organoids," of which 180 were included. We summarized the research progress of brain organoids over the past eight years by categorizing and refining the findings. Our analysis shows that brain organoids have achieved significant success in simulating brain development in vitro, leading to the establishment and refinement of 3D brain organoid models for disease research. Brain organoids have been widely applied to explore disease-related mechanisms, yielding promising results and opening avenues for further research on the human brain. In this review, we summarize the progress of brain organoids in three areas: culture methods, disease-related research, and brain exploration.

Schizophrenia, clinical and basic research at NIMH: A 75 Year retrospective

ObjectiveIn 2024, NIMH is celebrating its 75th anniversary. At the Congressional hearings preceding its initial funding in 1949, witnesses stressed the need for NIMH to carry out clinical and basic research to find the causes and better treatments for severe mental illnesses. Patients with schizophrenia alone were said to occupy one quarter of all hospital beds in the U.S. We therefore sought to ascertain the relative importance of clinical and basic research funded by NIMH over the life of the institute, using schizophrenia as our primary example. MethodsWe used information of published studies, from the NIMH website, and from NIMH employees both past and present. ResultsDuring its first 40 years, NIMH funded clinical and basic research approximately equally. That changed in the 1990s when the funding of the Human Genome Project started a shift in research resources from clinical to basic. By 2015, clinical research at NIMH had been reduced to 10 % of the research portfolio. This decline has continued and been well documented. For example, between 2006 and 2023, NIMH-funded extramural drug trials for schizophrenia and bipolar disorder decreased by 95 %. To clearly illustrate the decline of schizophrenia research at NIMH, research for the 5-year period from 1984 to 1988 was compared with research from 2018 to 2022. ConclusionsIn summary, data suggests that over the past 3 decades NIMH has reduced clinical research on severe mental illnesses by at least 90 %. We therefore recommend that NIMH re-establish clinical research on severe mental illnesses as a priority, as originally intended by Congress; that NIMH spend at least 50 % of all disease-related research dollars on clinical research; and that this distribution be documented in an existing and publicly available database.

Effect of HPV Oncoprotein on Carbohydrate and Lipid Metabolism in Tumor Cells.

High-risk HPV infection accounts for 99.7% of cervical cancer, over 90% of anal cancer, 50% of head and neck cancers, 40% of vulvar cancer, and some cases of vaginal and penile cancer, contributing to approximately 5% of cancers worldwide. The development of cancer is a complex, multi-step process characterized by dysregulation of signaling pathways and alterations in metabolic pathways. Extensive research has demonstrated that metabolic reprogramming plays a key role in the progression of various cancers, such as cervical, head and neck, bladder, and prostate cancers, providing the material and energy foundation for rapid proliferation and migration of cancer cells. Metabolic reprogramming of tumor cells allows for the rapid generation of ATP, aiding in meeting the high energy demands of HPV-related cancer cell proliferation. The interaction between Human Papillomavirus (HPV) and its associated cancers has become a recent focus of investigation. The impact of HPV on cellular metabolism has emerged as an emerging research topic. A significant body of research has shown that HPV influences relevant metabolic signaling pathways, leading to cellular metabolic alterations. Exploring the underlying mechanisms may facilitate the discovery of biomarkers for diagnosis and treatment of HPV-associated diseases. In this review, we introduced the molecular structure of HPV and its replication process, discussed the diseases associated with HPV infection, described the energy metabolism of normal cells, highlighted the metabolic features of tumor cells, and provided an overview of recent advances in potential therapeutic targets that act on cellular metabolism. We discussed the potential mechanisms underlying these changes. This article aims to elucidate the role of Human Papillomavirus (HPV) in reshaping cellular metabolism and the application of metabolic changes in the research of related diseases. Targeting cancer metabolism may serve as an effective strategy to support traditional cancer treatments, as metabolic reprogramming is crucial for malignant transformation in cancer.

A Nanofluorescent Probe for Evaluating the Fluctuation of Aminopeptidase N in Nonalcoholic Fatty Liver Disease and Hepatic Fibrosis.

Aminopeptidase N (APN/CD13) is a widely expressed transmembrane ectoenzyme that is crucial for maintaining normal physiological activities. It exhibits abnormal activity closely associated with hepatic fibrosis and nonalcoholic fatty liver disease (NAFLD). Therefore, there is a high demand for noninvasive detection of aminopeptidase N (APN) in the diagnosis and research of related diseases. Here, we developed a small molecule fluorescent probe, Hcy-APN, which is a fluorescent probe with high sensitivity and selectivity for the detection of APN. Furthermore, we synthesized the fluorescent nanoprobe Hcy-APN@MSN by self-assembling Hcy-APN and mesoporous silica nanoparticles in solution using a combination of molecular probe design and nanofunctionalization strategies. The detection limit of this probe was 1.5 ng/mL. Hcy-APN@MSN exhibits more stable spectral characteristics compared to Hcy-APN and is suitable for detecting APN activity in live cells and mice. Hcy-APN@MSN was utilized for in vivo and intracellular imaging of NAFLD and hepatic fibrosis at different stages, as well as for a systematic assessment of APN levels in the liver. The results confirm an elevation in the expression levels of APN in NAFLD and hepatic fibrosis models. Furthermore, we investigated the inhibitory effect of the APN inhibitor bestatin in nonalcoholic fatty liver and hepatic fibrosis disease models, confirming its regulatory effect on APN levels in cells and in vivo in both disease models. Therefore, this study may offer diagnostic possibilities for detecting NAFLD and hepatic fibrosis.

Explore the Value of Multi-Parameter MRI in Non-Invasive Assessment of Prognostic Risk and Oxford Classification in Children with IgAN or IgAVN.

To explore the Oxford classification and prognostic risk stratification of the non-invasive evaluation of immunoglobulin A nephropathy (IgAN) or immunoglobulin A vasculitis with nephritis (IgAVN) in children using multiparametric magnetic resonance imaging (MRI). Forty-four children diagnosed with IgAN or IgAVN were included. Patients with 80-month risk scores >10% were categorized as the high-risk group, while others constituted the low-risk group. The T2* and apparent diffusion coefficient (ADC) values of the renal cortex and medulla were measured. Clinical and pathological parameters were also assessed. Univariate and multivariate logistic regression analyses were performed to identify the indicators associated with the high-risk group. Receiver operating characteristic (ROC) curves were drawn and the areas under the curve (AUCs) were calculated to evaluate the diagnostic performance variables for differentiating the high-risk group from the low-risk group. Only the T2*Cortex and mean arterial pressure (MAP) were independently reliable in both the univariate and multivariate analyses. The AUCs for differentiating the high-risk group from the low-risk group of T2*Cortex, MAP, and their combination model were 0.907, 0.881, and 0.947, respectively. Multiparametric MRI parameters, especially T2* values, could be used as new biomarkers to provide a new dimension in chronic kidney disease-related research and could play an important role in the non-invasive prognosis of children with IgAN or IgAVN.

Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases.

Globally, millions of individuals are impacted by neurodegenerative disorders including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Although a great deal of energy and financial resources have been invested in disease-related research, breakthroughs in therapeutic approaches remain elusive. The breakdown of cells usually happens together with the onset of neurodegenerative diseases. However, the mechanism that triggers neuronal loss is unknown. Lipid peroxidation, which is iron-dependent, causes a specific type of cell death called ferroptosis, and there is evidence its involvement in the pathogenic cascade of neurodegenerative diseases. However, the specific mechanisms are still not well known. The present article highlights the basic processes that underlie ferroptosis and the corresponding signaling networks. Furthermore, it provides an overview and discussion of current research on the role of ferroptosis across a variety of neurodegenerative conditions.

Global trends in diabetic eye disease research from 2012 to 2021.

JOURNAL/nrgr/04.03/01300535-202410000-00032/figure1/v/2024-02-06T055622Z/r/image-tiff Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries--the United States, China, Japan, the United Kingdom, Spain, Germany, and France--by searching for all global diabetic eye disease journal articles in the Web of Science and PubMed databases, all global registered clinical trials in the ClinicalTrials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority (89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema (9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development (58.19%). Approximately half of the trials (49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic (40 out of 1830; 2.19%) and diabetic eye disease (3 out of 1830; 0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

Design and synthesis of a novel fluorescent probe for the detection of bisulfite in plant and zebrafish

Sulfur dioxide (SO2) and its derivative bisulfite (SO32−/HSO3−) have a serious impact on the human health and environment. Therefore, the development of highly sensitive and specific detection methods for SO2 and its derivative is of great significance for environmental monitoring, food safety, and related disease research. In this paper, probe TPN-DP based on the triphenylamine fluorophore was developed to enable the imaging and detection of HSO3− in plant and zebrafish. In PBS buffer solution, the designed probe TPN-DP can react with HSO3− by highly selective nucleophilic addition reaction, leading to a sensitive change in the color of probe TPN-DP solution from pink to colorless. The changes in fluorescence and color can be easily recognized by the naked eye. Moreover, probe TPN-DP exhibited a fast response time of 8 min, high sensitivity of 19.4 nM, and excellent selectivity for sensing HSO3−. With the help of probe TPN-DP, the detection of HSO3− was successfully achieved in water sample and various biological systems, including onion epidermal cells, tobacco seedling roots, and zebrafish. These findings not only provide valuable insights into the biological role of HSO3− but also offer a promising analytical method for efficient HSO3− recognition.

A scientometric analysis and visualization of Pott's disease; 2000-2021

Aims: Spinal tuberculosis, or Pott's disease, is a bacterial infection of the spine, which is primarily brought on by the bacterium Mycobacterium tuberculosis. In this study, Pott's disease-related research papers from the Web of Science database were examined scientometrically. The study's time frame is between 2000 and 2021. To shed light on the trends and advancements in research on Pott's disease, bibliometric techniques are used in the analysis. 
 Methods: A literature search on spinal tuberculosis was carried out in November 2022 using the WOS search engine. Using specific retrieval keywords, the search covered the years 2000 through 2021. Titles, document types, publication years, author details, affiliations, keywords, funding sponsors, journal names, abstracts, and citations were examined. The data was further processed for both quantitative and qualitative analysis using VOSviewer (1.6.18).
 Results: A total of 892 papers from 2000 to 2021 were examined based on search parameters. 430 of these were released as Open Access articles. 81.0% of them were in the Science Citation Index Expanded. The publications came from 77 different nations, China dominated research on Pott's disease with 306 papers, followed by India with 147 and the United States with 86. The investigation revealed a rising trend in recent years, pointing to a rise in interest in Pott's disease. Research fields like neurology and orthopedics made important advances. Notably, 7.7% of the research' funding for Pott's disease publications came from the Chinese National Natural Science Foundation. The leading publishing journal has become the European Spine Journal.
 Conclusion: The data shows that China has played a significant role in Pott's disease research, followed by India and the United States. The survey also reveals a growing need for PD research, notably in the disciplines of orthopedics and neurology.

Progress in research on the role played by myeloid-derived suppressor cells in liver diseases.

Myeloid-derived suppressor cells (MDSCs) refer to a group of immature myeloid cells with potent immunosuppressive capacity upon activation by pathological conditions. Because of their potent immunosuppressive ability, MDSCs have garnered extensive attention in the past few years in the fields of oncology, infection, chronic inflammation and autoimmune diseases. Research on MDSCs in liver diseases has gradually increased, and their potential therapeutic roles will be further explored. This review presents a summary of the involvement and the role played by MDSCs in liver diseases, thus identifying their potential targets for the treatment of liver diseases and providing new directions for liver disease-related research.

NIRS-Based Muscle Oxygenation Is Not Suitable to Compute Convective and Diffusive Components of O 2 Transport at V̇O 2max : Response to Manferdelli, Barstow, and Millet.

1Department of Molecular Medicine, University of Pavia, Pavia, ITALY 2Institute of Biomedical Technologies, National Research Council, Milan, ITALY 3Department of Medicine, University of Udine, Udine, ITALY 4Division of Respiratory and Critical Care Physiology and Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA Address for Correspondence: Simone Porcelli, MD, PhD, Assistant Professor in Human Physiology Institute of Physiology, Department of Molecular Medicine University of Pavia, Italy, Via Forlanini 6, 27100 Pavia – Italy; Phone: +39 0382987538; E-mail: [email protected] Conflict of Interest and Funding Source: The authors have no conflicts of interest to disclose. Harry Rossiter is supported by grants from NIH (R01HL151452, R01HL153460, P50HD098593, R01DK122767, P2CHD086851) and the Tobacco Related Disease Research Program (T31IP1666). He reports consulting fees from Omniox Inc., and is involved in contracted clinical research with Boehringer Ingelheim, GlaxoSmithKline, Novartis, AstraZeneca, Astellas, United Therapeutics, Genentech and Regeneron. He is a visiting Professor at the University of Leeds, UK. The views of the perspective are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. This perspective does not constitute endorsement by the American College of Sports Medicine.

NIRS-Based Muscle Oxygenation Is Not Suitable to Compute Convective and Diffusive Components of O 2 Transport at V̇O 2max.

1Department of Molecular Medicine, University of Pavia, Pavia, ITALY 2Institute of Biomedical Technologies, National Research Council, Milan, ITALY 3Department of Medicine, University of Udine, Udine, ITALY 4Division of Respiratory and Critical Care Physiology and Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA Address for Correspondence: Simone Porcelli, MD, PhD, Assistant Professor in Human Physiology Institute of Physiology, Department of Molecular Medicine University of Pavia, Italy, Via Forlanini 6, 27100 Pavia – Italy; Phone: +39 0382987538; E-mail: [email protected] Conflict of Interest and Funding Source: The authors have no conflicts of interest to disclose. Harry Rossiter is supported by grants from NIH (R01HL151452, R01HL153460, P50HD098593, R01DK122767, P2CHD086851) and the Tobacco Related Disease Research Program (T31IP1666). He reports consulting fees from Omniox Inc., and is involved in contracted clinical research with Boehringer Ingelheim, GlaxoSmithKline, Novartis, AstraZeneca, Astellas, United Therapeutics, Genentech and Regeneron. He is a visiting Professor at the University of Leeds, UK. The views of the perspective are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. This perspective does not constitute endorsement by the American College of Sports Medicine.

Comprehensive analysis of REST corepressors (RCORs) in pan-cancer.

REST corepressors (RCORs) are the core component of the LSD1/CoREST/HDACs transcriptional repressor complex, which have been revealed differently expressed in various cancers, but the therapeutic and prognostic mechanisms in cancer are still poorly understood. In this study, we analyzed expression, prognostic value, molecular subtypes, genetic alteration, immunotherapy response and drug sensitivity of RCORs in pan-cancer. Clinical correlation, stemness index, immune infiltration and regulatory networks of RCORs in hepatocellular carcinoma (HCC) were detected through TCGA and GSCA database. In-vitro experiments were conducted to explore the role of RCOR1 in HCC cells. The expression of RCORs varied among different cancers, and have prognostic values in several cancers. Cancer subtypes were categorized according to the expression of RCORs with clinical information. RCORs were significantly correlated with immunotherapy response, MSI, drug sensitivity and genetic alteration in pan-cancer. In HCC, RCORs were considered as potential predictor of stemness and also had association with immune infiltration. The ceRNA-TF-kinase regulatory networks of RCORs were constructed. Besides, RCOR1 acts as an oncogene in HCC and promotes the proliferation of HCC cells by inhibiting cell cycle arrest and cell apoptosis. Taken together, our study revealed the potential molecular mechanisms of RCORs in pan-cancer, offering a benchmark for disease-related research.

Development of Scaffold-Free Three-Dimensional Cholangiocyte Organoids to Study the Progression of Primary Sclerosing Cholangitis

Organoids are novel invitro models to study intercellular cross talk between the different types of cells in disease pathophysiology. To better understand the underlying mechanisms driving the progression of primary sclerosing cholangitis (PSC), scaffold-free multicellular three-dimensional cholangiocyte organoids (3D-CHOs) were developed using primary liver cells derived from normal subjects and patients with PSC. Human liver samples from healthy donors and patients with PSC were used to isolate primary cholangiocytes [epithelial cell adhesion molecule (EpCam)+/ cytokeratin-19+], liver endothelial cells (CD31+), and hepatic stellate cells (HSCs; CD31-/CD68-/desmin+/vitamin A+). 3D-CHOs were formed using cholangiocytes, HSCs, and liver endothelial cells, and kept viable for up to 1 month. Isolated primary cell lines and 3D-CHOs were further characterized by immunofluorescence, quantitative RT-PCR, and transmission electron microscopy. Transcription profiles for cholangiocytes (SOX9, CFTR, EpCAM, AE, SCT, and SCTR), fibrosis (ACTA2, COL1A1, DESMIN, and TGFβ1), angiogenesis (PECAM, VEGF, CDH5, and vWF), and inflammation (IL-6 and TNF-α) confirmed PSC phenotypes of 3D-CHOs. Because cholangiocytes develop a neuroendocrine phenotype and express neuromodulators, confocal immunofluorescence was used to demonstrate localization of the neurokinin-1 receptor within cytokeratin-19+ cholangiocytes and desmin+ HSCs. Moreover, 3D-CHOs from patients with PSC confirmed PSC phenotypes with up-regulated neurokinin-1 receptor, tachykinin precursor 1, and down-regulated membrane metalloendopeptidase. Scaffold-free multicellular 3D-CHOs showed superiority as an invitro model in mimicking PSC invivo phenotypes compared with two-dimensional cell culture, which can be used in PSC disease-related research.

Global research trends on diet and nutrition in Crohn's disease.

Crohn's disease represents a challenge for patients concerned with the modified diet regimen as well as practitioners who seek the best nutritional therapy. Crohn's disease can alter the body's ability to digest food and to absorb nutrients, resulting in severe vitamin deficiencies, malnutrition and sometimes life-threatening complications. However, a comprehensive bibliometric analysis is lacking to map the current links between nutrition and Crohn's disease in terms of the number of citations, geographic distribution and growth trends of publications. To introduce the current state of research as well as hotspots in the field of nutrition and Crohn's disease from a bibliometric standpoint. We searched the Scopus database and selected the relevant literature on nutrition and Crohn's disease that met the inclusion criteria. We analyzed the publication trends and research hotspots by using video object segmentation viewer software. We included 1237 publications. The number of documents published each year has increased steadily. The United States and the University of Otago, Christchurch, have had the highest productivity, with 208 (16.81%) and 29 (2.34%) documents, respectively. The "role of exclusive enteral nutrition for complicated Crohn's disease" and "manipulation of the gut microbiota as a key target for Crohn's disease" were the major research areas in 2016-2021, and they could be extensively investigated in the future. Meanwhile, research on "malnutrition in patients with Crohn's disease" appeared to be an area that attracted more research attention before 2016. This is the first bibliometric analysis to map the knowledge structure and trends regarding nutrition in Crohn's disease research over the past two decades. The results provide a comprehensive summary and identification of the frontiers of nutrition and Crohn's disease-related research, which may be used as a resource by researchers in the field.

Rapid imaging of unsaturated lipids at isomer level using photoepoxidation

Unsaturated lipids play an essential role in living organisms, and their different isomers show significant functional differences. Therefore, in situ characterization of unsaturated lipids in tissues needs to be extended to isomer level. However, the exposure of tissue sections to an open environment for a long time may cause cell autolysis or corruption, and current unsaturated lipid imaging methods still face challenges in efficiency. This paper proposes an imaging method based on photoepoxidation coupled with air-flow-assisted desorption electrospray ionization mass spectrometry (AFADESI-MS) to rapidly realize the spatial characterization of unsaturated lipids at the isomer level. The technique has a fast response speed, high epoxide yield (>80%), and high diagnostic ion abundance. After 0.5 min of photoepoxidation, the derivation product yield ratio reached 24.6%. This method rapidly identified six glycerophospholipid isomers containing an 18:1 acyl chain in normal rat liver tissue. Then the imaging method was applied in nude mice lung cancer tissue and human thyroid cancer tissue, with only 3 min photoepoxidation. Results successfully characterized the location and range of unsaturated lipid isomers and revealed their enrichment in tumor tissue. In addition, the experiment shows that the variational trend of the ratio of unsaturated lipid isomers in different types of tumor samples is different. Based on the advantages of efficiency and convenience, this method is prospective for screening unsaturated lipid markers and pathological research of related diseases.

Review of Motion Simulation of Particulate Matter in the Respiratory System and Further CFD Simulations on COVID-19

Respirable particulate matter (RSP) is currently very harmful to the human body, potentially causing pulmonary silicosis, allergic rhinitis, acute bronchitis, and pulmonary heart disease. Therefore, the study of the deposition pattern of RSP in the human respiratory system is key in the prevention, treatment, and research of related diseases, whereby the main methods are computer simulation, in vitro solid models, and theoretical analysis. This paper summarizes and analyzes past deposition of RSP in the respiratory tract and also describes them in specific case studies such as COPD and COVID-19 patients, based on the review of the evidence, direction, and focus of future research focusing on simulation, experimentation, and related applications of RSP deposition in the respiratory tract.

The status and trends of mitochondrial dynamics research: A global bibliometric and visualized analysis

BackgroundMitochondria are remarkably dynamic organelles encapsulated by bilayer membranes. The dynamic properties of mitochondria are critical for energy production.AimsThe aim of our study is to investigate the global status and trends of mitochondrial dynamics research and predict popular topics and directions in the field.MethodsPublications related to the studies of mitochondrial dynamics from 2002 to 2021 were retrieved from Web of Science database. A total of 4,576 publications were included. Bibliometric analysis was conducted by visualization of similarities viewer and GraphPadPrism 5 software.ResultsThere is an increasing trend of mitochondrial dynamics research during the last 20 years. The cumulative number of publications about mitochondrial dynamics research followed the logistic growth model mathrm{f}(x)=mathrm{a}/left[1+{e}^{(b-cx)}right]. The USA made the highest contributions to the global research. The journal Biochimica et Biophysica Acta (BBA)—Molecular Cell Research had the largest publication numbers. Case Western Reserve University is the most contributive institution. The main research orientation and funding agency were cell biology and HHS. All keywords related studies could be divided into three clusters: “Related disease research”, “Mechanism research” and “Cell metabolism research”.ConclusionsAttention should be drawn to the latest popular research and more efforts will be put into mechanistic research, which may inspire new clinical treatments for the associated diseases.

Dermal thirdhand smoke exposure induces oxidative damage, initiates skin inflammatory markers, and adversely alters the human plasma proteome.

SummaryBackgroundThirdhand smoke (THS) exposure correlated with significant metabolism of carcinogenic chemicals and the potential to cause detrimental health effects. Human harm research of THS exposure is limited to one other study and overall, there is a general lack of knowledge of the human health responses to THS exposure.MethodsThis was a clinical investigation to evaluate the health effects of 3-h dermal THS exposure from urine and plasma. 10 healthy, non-smoking subjects were recruited for dermal exposure for 3 h exposed to clothing impregnated with filtered clean air or THS. Exposures to clean air or THS occurred 20-30 days apart.FindingsIn THS-exposed group, there was a significant elevation of urinary 8-OHdG, 8-isoprostane, protein carbonyls. The THS 3-h exposure identified proteomics pathways of inflammatory response (p=2.18 × 10−8), adhesion of blood cells (p=2.23 × 10−8), atherosclerosis (p=2.78 × 10−9), and lichen planus (p=1.77 × 10−8). Nine canonical pathways were significantly activated including leukocyte extravasation signaling (z-score=3.0), and production of nitric oxide and reactive oxygen in macrophages (z-score=2.1). The THS 22-h proteomics pathways revealed inflammation of organ (p=3.09 × 10−8), keratinization of the epidermis (p=4.0 × 10−7), plaque psoriasis (p=5.31 × 10−7), and dermatitis (p=6.0 × 10−7). Two activated canonical pathways were production of nitric oxide and reactive oxygen in macrophages (z-score=2.646), and IL-8 signaling (z-score=2.0).InterpretationThis is a clinical study demonstrating that acute dermal exposure to THS mimics the harmful effects of cigarette smoking, alters the human plasma proteome, initiates mechanisms of skin inflammatory disease, and elevates urinary biomarkers of oxidative harm.FundingFunding was provided by the Tobacco Related Disease Research Program (TRDRP) 24RT-0037 TRDRP, 24RT-0039 TRDRP, and 28PT-0081 TRDRP.

Research hotspot and trend analysis in the diagnosis of inflammatory bowel disease: A machine learning bibliometric analysis from 2012 to 2021.

AimsThis study aimed to conduct a bibliometric analysis of the relevant literature on the diagnosis of inflammatory bowel disease (IBD), and show its current status, hot spots, and development trends.MethodsThe literature on IBD diagnosis was acquired from the Science Citation Index Expanded of the Web of Science Core Collection. Co-occurrence and cooperation relationship analysis of authors, institutions, countries, journals, references, and keywords in the literature were carried out through CiteSpace software and the Online Analysis platform of Literature Metrology. At the same time, the relevant knowledge maps were drawn, and the keywords cluster analysis and emergence analysis were performed.Results14,742 related articles were included, showing that the number of articles in this field has increased in recent years. The results showed that PEYRIN-BIROULET L from the University Hospital of Nancy-Brabois was the author with the most cumulative number of articles. The institution with the most articles was Mayo Clin, and the United States was far ahead in the article output and had a dominant role. Keywords analysis showed that there was a total of 818 keywords, which were mainly focused on the research of related diseases caused or coexisted by IBD, such as colorectal cancer and autoimmune diseases, and the diagnosis and treatment methods of IBD. Emerging analysis showed that future research hotspots and trends might be the treatment of IBD and precision medicine.ConclusionThis research was the first bibliometric analysis of publications in the field of IBD diagnosis using visualization software and data information mining, and obtained the current status, hotspots, and development of this field. The future research hotspot might be the precision medicine of IBD, and the mechanism needed to be explored in depth to provide a theoretical basis for its clinical application.