Long Non-Coding RNA Nuclear-Enriched Abundant Transcript 1 (NEAT1) Facilitates Foam Cell Formation and Atherosclerosis Progression Through the miR-17-5p/Itchy E3 Ubiquitin Protein Ligase (ITCH)/Liver Kinase B1 (LKB1) Axis.

BACKGROUND: Foam cell formation is an important step for atherosclerosis (AS) progression. We investigated the mechanism by which the long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) regulates foam cell formation during AS progression.Methods and Results: An in vivo AS model was created by feeding ApoE-/-mice a high-fat diet. Oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages were used as a cellular AS model. Interactions between NEAT1, miR-17-5p, itchy E3 ubiquitin protein ligase (ITCH) and liver kinase B1 (LKB1) were analyzed. NEAT1 and ITCH were highly expressed in clinical samples collected from 10 AS patients and in ox-LDL-treated macrophages, whereas expression of both miR-17-5p and LKB1 was low. ITCH knockdown inhibited ox-LDL-induced lipid accumulation and LDL uptake in macrophages. Mechanistically speakingly, ITCH promoted LDL uptake and lipid accumulation in macrophages by mediating LKB1 ubiquitination degradation. NEAT1 knockdown reduced LDL uptake and lipid accumulation in macrophages and AS progression in vivo. NEAT1 promoted ITCH expression in macrophages by acting as a sponge for miR-17-5p. Inhibition of miR-17-5p facilitated ox-LDL-induced increase in LDL uptake and lipid accumulation in macrophages, which was reversed by NEAT1/ITCH knockdown. CONCLUSIONS: NEAT1 accelerated foam cell formation during AS progression through the miR-17-5p/ITCH/LKB1 axis.

Work-related stress and atopic dermatitis: Results from the study on occupational allergy risks.

Chronic stress at work is ubiquitous in modern societies. However, its influence on atopic dermatitis (AD) has hardly been investigated. This study aimed to elucidate the association between work-related stress and AD via a longitudinal study. The analysis comprised data from three phases (2002-2003, 2007-2009, 2017-2018) of the prospective Study on Occupational Allergy Risks (SOLAR), including 1,240 young adults aged 16 to 18 years at baseline (61% female) who were originally recruited for the International Study of Asthma and Allergies in Childhood Phase II in 1995-1996. AD was assessed at all three phases based on self-reports of a physician's diagnosis and symptoms. Work-related stress was measured at all three periods using the work discontent and work overload scales from the Trier Inventory for the Assessment of Chronic Stress with adaptions to school and university. Generalized estimating equations were used to analyze the association between stress and AD, treating work discontent and work overload first as continuous and then as categorical exposure variables. We observed 50 AD cases (4%) at SOLAR I, 48 (4%) at SOLAR II, and 42 (3%) at SOLAR III. A one-point increase in the work discontent score was associated with an odds ratio (OR) for AD of 1.05 (95% confidence interval [CI], 1.00-1.10). The respective increase in the work overload score led to an OR of 1.03 (95% CI, 0.99-1.06). In the categorical analysis, there was no clear indication of elevated odds of AD in the highest vs. lowest exposure group (4th vs. 1st quartile: OR, 1.53; 95% CI, 0.92-2.53 for work discontent; OR, 1.38, 95% CI, 0.83-2.27 for work overload). Altogether, we observed limited to no evidence for an association between work-related stress and AD. Our study's ability to detect stronger evidence may have been compromised by shortcomings such as nondifferential misclassification of the outcome or insufficient statistical precision due to small numbers of AD cases. Another explanation could be that AD predominantly becomes evident in childhood, not in adulthood.

Circular RNA ITCH attenuates the progression of nasopharyngeal carcinoma by inducing PTEN upregulation via miR-214.

BACKGROUND: Circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH) has previously been reported to play a key role in carcinogenesis. Nevertheless, the role of circ-ITCH in nasopharyngeal carcinoma (NPC) remains to be explored. METHODS: Gene expression analysis was performed using a quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. The role of circ-ITCH in NPC was explored using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, colony formation, transwell invasion, scratch healing and xenograft tumor assays. Furthermore, luciferase reporter assay was carried out to assess the interactions among circ-ITCH, microRNA-214 (miR-214) and phosphatase and tensin homolog (PTEN). RESULTS: The levels of circ-ITCH and PTEN were decreased, whereas the level of miR-214 was increased in NPC tissues collected from 28 subjects compared to normal nasopharynx tissues collected from 15 subjects. Moreover, a negative correlation between circ-ITCH and miR-214 expression and a positive correlation between circ-ITCH and PTEN expression were observed in NPC tissues. Downregulation of circ-ITCH expression was also observed in NPC cell lines. In addition, upregulation of circ-ITCH markedly inhibited NPC cell proliferation, migration and invasion. Furthermore, circ-ITCH was confirmed to exert its function by sponging miR-214. PTEN was found to be a direct target gene of miR-214 and its expression was negatively correlated with miR-214 expression in NPC tissues. Moreover, our results showed that the circ-ITCH/miR-214 axis regulated NPC proliferation, migration and invasion through regulating the expression of PTEN. Upregulation of circ-ITCH or PTEN blocked miR-214-mediated promotion of NPC tumorigenesis in vitro. Additionally, upregulation of circ-ITCH also suppressed NPC tumorigenesis in vivo. CONCLUSIONS: The present study demonstrated that circ-ITCH suppressed NPC tumorigenesis by upregulating PTEN expression through interacting with miR-214, thus proposing a novel mechanism for NPC inhibition.

Footedness for scratching itchy eyes in rodents.

The neural bases of itchy eye transmission remain unclear compared with those involved in body itch. Here, we show in rodents that the gastrin-releasing peptide receptor (GRPR) of the trigeminal sensory system is involved in the transmission of itchy eyes. Interestingly, we further demonstrate a difference in scratching behaviour between the left and right hindfeet in rodents; histamine instillation into the conjunctival sac of both eyes revealed right-foot biased laterality in the scratching movements. Unilateral histamine instillation specifically induced neural activation in the ipsilateral sensory pathway, with no significant difference between the activations following left- and right-eye instillations. Thus, the behavioural laterality is presumably due to right-foot preference in rodents. Genetically modified rats with specific depletion of Grpr-expressing neurons in the trigeminal sensory nucleus caudalis of the medulla oblongata exhibited fewer and shorter histamine-induced scratching movements than controls and eliminated the footedness. These results taken together indicate that the Grpr-expressing neurons are required for the transmission of itch sensation from the eyes, but that foot preference is generated centrally. These findings could open up a new field of research on the mechanisms of the laterality in vertebrates and also offer new potential therapeutic approaches to refractory pruritic eye disorders.

Ubiquitination of interleukin-1α is associated with increased pro-inflammatory polarization of murine macrophages deficient in the E3 ligase ITCH.

Macrophages play critical roles in homeostasis and inflammation. Macrophage polarization to either a pro-inflammatory or anti-inflammatory status is controlled by activating inflammatory signaling pathways. Ubiquitination is a posttranslational modification that regulates these inflammatory signaling pathways. However, the influence of protein ubiquitination on macrophage polarization has not been well studied. We hypothesized that the ubiquitination status of key proteins in inflammatory pathways contributes to macrophage polarization, which is regulated by itchy E3 ubiquitin ligase (ITCH), a negative regulator of inflammation. Using ubiquitin proteomics, we found that ubiquitination profiles are different among polarized murine macrophage subsets. Interestingly, interleukin-1α (IL-1α), an important pro-inflammatory mediator, was specifically ubiquitinated in lipopolysaccharide-induced pro-inflammatory macrophages, which was enhanced in ITCH-deficient macrophages. The ITCH-deficient macrophages had increased levels of the mature form of IL-1α and exhibited pro-inflammatory polarization, and reduced deubiquitination of IL-1α protein. Finally, IL-1α neutralization attenuated pro-inflammatory polarization of the ITCH-deficient macrophages. In conclusion, ubiquitination of IL-1α is associated with increased pro-inflammatory polarization of macrophages deficient in the E3 ligase ITCH.

Prurigo Simplex or "Itchy Red Bump" Disease: Review and Case Series.

Prurigo simplex or "itchy red bump" disease is a controversial pruritic papular eruption. The objective of this study was to delineate the diagnostic criteria for this disease. A PubMed search was performed for: "prurigo simplex", "prurigo simplex subacuta", "subacute prurigo", "chronic papular dermatitis in adults" and "itchy red bump disease". Medical charts of patients with prurigo diagnoses in a university setting were analysed. The literature search revealed 32 relevant studies (431 patients) on different aspects of the disease. Out of 50 patients with prurigo diagnoses, 5 patients (4 women, mean age at onset 54 years) matched the description in literature. Small, severely itchy papules without secondary skin lesions continued to appear for years (mean 5.6 years). Skin biopsies revealed lymphocytic perivascular infiltrates, few eosinophils and occasionally spongiosis. Treatment with long-term metho-trexate or cyclosporine cleared the symptoms. Some major and minor diagnostic criteria for prurigo simplex are proposed and compared with chronic prurigo.

[Modern aspects of inflammatory external ear diseases treatment]. / Sovremennye aspekty lecheniya vospalitel'nykh zabolevanii naruzhnogo ukha.

The article deals with the problem of inflammatory diseases of the external ear. A review of pruritic dermatoses of the external auditory canal was carried out. It has been shown that in chronic dermatoses, the contamination of the skin with bacterial and fungal pathogens significantly increases, which leads to a high risk of developing secondary infectious pathological processes. Treatment of dermatological inflammatory ear diseases includes careful daily hygiene of the external auditory canal and pharmacotherapy, a key aspect of which is the use of topical etiotropic, anti-inflammatory, and symptomatic drugs. The advantage of the combined drug candiderm is described, which, thanks to the unique combination of beclomethasone, gentamicin and clotrimazole in the composition, effectively relieves the symptoms of external ear dermatoses.

Prevalence of Asthma and Allergies and Risk of Relapse in Childhood Nephrotic Syndrome: Insight into Nephrotic Syndrome Cohort.

OBJECTIVE: To determine the lifetime prevalence of allergies in childhood nephrotic syndrome, the seasonality of presentation and relapses, and the impact of allergies on subsequent relapses. STUDY DESIGN: In a longitudinal cohort of children with nephrotic syndrome (ages 1-18 years), assessment for allergic diseases was conducted using the validated and modified version of the International Study of Asthma and Allergies in Childhood questionnaire at enrollment. Outcomes included frequently relapsing nephrotic syndrome, relapse rates, and the relapse-free duration after initial steroid therapy. RESULTS: Among 277 participants, the majority were male (65%) with a median age of 3.7 years (IQR 2.8-5.8) at presentation. A total of 64% reported lifetime allergies with 20% having asthma, 33% wheezing, 27% eczema, and 24% rhinitis. Over 3.3 years of follow-up, presence of asthma and allergies was not associated with frequently relapsing nephrotic syndrome (OR 1.20; 95% CI 0.60, 2.40), higher relapse rates (relative risk 0.95; 95% CI 0.71, 1.27), or risk of first relapse (hazard ratio 1.10; 95% CI 0.83, 1.47) compared with those with no history of allergic diseases. There was also no seasonal variation evident at initial presentation or frequency of relapses. CONCLUSIONS: Two-thirds of children with nephrotic syndrome at presentation have allergic symptoms and asthma; however, neither are associated with an increased frequency of relapses.

Comparison of reactivity to a metallic disc and 2% aluminium salt in 366 children, and reproducibility over time for 241 young adults with childhood vaccine-related aluminium contact allergy.

BACKGROUND: An aluminium hydroxide-adsorbed pertussis toxoid vaccine was studied in 76 000 children in the 1990s in Gothenburg, Sweden. Long-lasting itchy subcutaneous nodules at the vaccination site were seen in 745 participants. Of 495 children with itchy nodules who were patch tested for aluminium allergy, 377 were positive. In 2007-2008, 241 of the positive children were retested. Only in one third were earlier positive results reproduced. OBJECTIVES: To further describe patch test reactions to different aluminium compounds in children with vaccine-induced aluminium allergy. PATIENTS/METHODS: Positive patch test results for metallic aluminium (empty Finn Chamber) and aluminium chloride hexahydrate 2% petrolatum (pet.) were analysed in 366 children with vaccine-induced persistent itching nodules tested in 1998-2002. Of those, 241 were tested a second time (2007-2008), and the patch test results of the two aluminium preparations were analysed. RESULTS: Patch testing with aluminium chloride hexahydrate 2% pet. is a more sensitive way to diagnose aluminium contact allergy than patch testing with metallic aluminium. A general decrease in the strength of reactions to both aluminium preparations in 241 children tested twice was observed. CONCLUSIONS: Aluminium contact allergy can be diagnosed by patch testing without using metallic aluminium.

Weekly hair washing: The recommended solution for women with afro-textured hair to alleviate dandruff and scalp discomfort.

Dandruff and scalp discomfort are common concerns for women and men in Africa. Moreover, women with afro-textured hair are prone to scalp discomfort owing to irregular hair washing, frequent use of oil-based products on their scalp, and harsh chemical treatments. Current literature does not, however, provide data on the pathophysiological mechanisms of these conditions in this population. In this study, we investigated the mechanisms behind scalp discomfort and dandruff in women of African descent before and after hair washing. We conducted the in Durban, South Africa, over a 3-week period with 60 women of African descent aged 20-40 years. The respondents were equally divided into a "dandruff" and a "no dandruff" group, based on clinical grading of adherent dandruff by a dermatologist. Malassezia spp. and bacterial loads were quantified by quantitative polymerase chain reaction. Evaluations of scalp condition and sample collection were performed at five time points during the 3 weeks. Data on discomfort symptoms were collected via a self-assessment questionnaire. We observed that the dandruff severity peaked at the end of the first week after hair washing and plateaued from thereon in both groups. Dandruff was associated with higher Malassezia and bacterial load counts and there was a direct correlation between the Malassezia spp. load and dandruff score. Via self-assessment questionnaire responses submitted by participants, we observed that itching was the most pronounced scalp discomfort, compared with the sensation of tingling and burning at baseline, while an improvement of the scalp symptoms of dandruff and itch was observed in both groups after one hair wash. The study also showed that higher colonization with Malassezia spp. and bacteria is associated with dandruff independently of the time point, confirming a scalp microbiome contribution to the dandruff pathophysiology in the study population. The benefits of washing were, however, not sustained after 1 week and we thus recommend weekly hair washing for long-term management of dandruff and scalp itchiness in this population.

Papuloerythroderma of Ofuji in a 41-year-old woman.

Papuloerythroderma, described by Ofuji in 1984, is characterized by the occurrence of polygonal, erythematous-brown papules, covering the entire skin surface, except skin folds; these changes are accompanied by pruritus and eosinophilia. We report a case of a 41-year-old female patient with melanoerythroderma that has been intensifying since August 2010. The patient's personal and family history for atopy were negative. No triggering factors were identified in the course of hospitalizations. Preceding infections and neoplasms were excluded. The diagnosis of papuloerythroderma of Ofuji was established on the basis of major and minor criteria proposed by Torchia et al. The patient met all the five major criteria: 1) erythroderma-like eruption formed by coalescence of flat-topped, red-to-brown papules with a cobblestone-like appearance, 2) itch, 3) sparing of skin folds and creases, 4) histopathological exclusion of cutaneous lymphoma and other skin diseases, 5) absence of the causative factors such as tumors, infections, drugs and atopy. Regarding the 5 minor criteria, the patient met the following three: 1) peripheral (33.8%) and tissue eosinophilia, 2) elevated level of the total serum IgE (10935 IU/ml), 3) lymphopenia (6.6%). The patient went into remission after 9-month treatment with cyclosporine at a dose of 3 mg/kg.

Atopic Dermatitis: Diagnosis, Disparity, and Management in Children of Color.

Atopic dermatitis (AD), sometimes referred to as eczema, is the most common chronic skin condition in children. Children of color have a higher reported prevalence of AD compared with their White counterparts. The purpose of this article is to discuss the differences of AD in skin of color (SOC), including clinical findings and management, with an emphasis on early recognition to avoid more severe, persistent disease. School nurses are on the frontline for these students with their ability to guide families and help support students with AD in the school setting.

Endotoxin concentration and persistent eczema in early childhood.

Although endotoxin concentration in the environment is negatively associated with atopic dermatitis (AD) onset in early childhood, the association between endotoxin concentration in the environment and eczema resolution in children with preexisting eczema is unclear. The aim of this study was to evaluate the association between endotoxin concentration in house dust and eczema persistence in young children. The authors used data from children participating in JECS (Japan Environment and Children's Study). In children who had AD or AD-like lesions at the age of 1 year, the authors investigated the association between the prevalence of eczema at the age of 3 years and endotoxin concentration (categorized by quartiles) in the dust on children's mattresses at the ages of 1.5 and 3 years. This study included 605 children. Eczema was significantly less prevalent among children whose mattresses were in the second and third quartiles of endotoxin concentration when they were 18 months old than among children whose mattresses were in the first quartile (adjusted odds ratio, 0.57 [95% confidence interval, 0.35-0.93] and adjusted odds ratio, 0.49 [95% confidence interval, 0.29-0.83], respectively). Moreover, of the children with eczema at age 3 years, those whose mattresses had endotoxin concentrations in the first quartile had significantly worse sleep disturbance caused by itchy rash (>1 time per week) than did those whose mattresses were in the third and fourth quartiles (20.0% vs 3.3% and 3.7%, both p values < 0.01). The findings indicate that low endotoxin exposure is associated with a higher prevalence of persistent eczema during early childhood.

Targeting a novel circITCH/miR-421/BTG1 axis is effective to suppress the malignant phenotypes in hepatocellular carcinoma (HCC) cells.

Circular RNA-based competing endogenous RNA (ceRNA) networks contribute to the initiation and development of various types of cancer, including hepatocellular carcinoma (HCC). Although a novel circular RNA itchy E3 ubiquitin protein ligase (circITCH) is identified as a tumor suppressor in HCC, its detailed molecular mechanisms have not been fully delineated. The present study was designed to resolve this issue, and we firstly verified that circITCH suppressed the malignant phenotypes in HCC cells by regulating a novel miR-421/B-cell translocation gene 1 (BTG1) axis. Specifically, through performing the Real-Time qPCR analysis, we noticed that circITCH expression in HCC tumor tissues or cell lines were significantly lower than that in adjacent normal tissues or normal hepatocytes, and the expression levels of circITCH were negatively correlated with tumor size and TNM stage in HCC patients. Next, our functional experiments confirmed that overexpression of circITCH induced cell cycle arrest and apoptosis, and reduced cell viability and colony forming ability in Hep3B and Huh7 cells. Mechanically, bioinformatics analysis, RNA immunoprecipitation and luciferase reporter assay demonstrated that circITCH served as RNA sponges for miR-421 to elevate BTG1 levels in HCC cells. The rescuing experiments verified that upregulation of miR-421 promoted cell viability and colony formation, and reduced apoptosis, which were abrogated by overexpression of circITCH or BTG1. In conclusion, this study identified a novel circITCH/miR-421/BTG1 axis that restrained the development of HCC, and our findings provided novel biomarkers for the treatment of this disease.

Hell's Itch: A Unique Reaction to UV Exposure.

We present a survey-based exploration of Hell's Itch, a severe dermatologic reaction often mistaken for sunburn, that reveals distinct symptoms including intense pain, unrelenting itching, paresthesia, and even suicidal ideation, differentiating it from a typical sunburn.

The Itchy Truth About Scabies: A Case of Asymptomatic Carrier Transmission and Treatment Failure.

Scabies, a common and highly contagious skin infestation, is caused by the mite Sarcoptes scabiei var. hominis. Identifying individuals with scabies often poses a diagnostic challenge, as its clinical features resemble other dermatologic conditions such as drug reactions, atopic dermatitis, and contact dermatitis. Furthermore, the cutaneous manifestations arise from delayed-type immunologic reactions to the mites and their byproducts, allowing some individuals to carry the mite without showing symptoms. The significant transmissibility of scabies, along with the potential for asymptomatic carriers, creates multiple treatment hurdles for cohabiting individuals, as the failure to treat all close contacts can result in re-infestation. This report presents the case of a 46-year-old Vietnamese male who suffered from a worsening erythematous, scaly, and pruritic rash for four months. Despite being prescribed topical corticosteroids by three different dermatologists, his rash persisted. Upon thorough evaluation, scabies was diagnosed. The patient was treated with scabicidal agents, which initially alleviated his symptoms; however, three weeks later, his symptoms resurfaced. Further investigation revealed that his wife was an asymptomatic carrier who had not received treatment. This case highlights the clinical features, pathogenesis, and treatment options for scabies while emphasizing the importance of promptly identifying and treating all close contacts.

Rapid Web-Based Recruitment of Patients With Psoriasis: Multinational Cohort Study.

BACKGROUND: Wide-ranging patient recruitment not restricted to the location of the investigator will provide a better representation of the patient population in clinical studies. OBJECTIVE: Our goal was to assess the feasibility of a broad web-based recruitment strategy in an 8-week observational study of 500 study participants with psoriasis and healthy controls from locations remote from the investigator and to assess the cost associated with each participant. METHODS: A decentralized team in Denmark recruited patients with psoriasis and healthy controls using Google and Facebook advertisements and posts to Facebook groups. All individuals were screened via the internet, and patients diagnosed with psoriasis were included. Questionnaires regarding itch and sleep were completed by both groups at inclusion, week 4, and week 8. RESULTS: During a 2-week recruitment period, 12,887 unique advertisement views were registered, and 839 participants were enrolled, of which 507 completed the study (220 with psoriasis and 287 healthy controls) with a retention rate of 60.4%. Participants were recruited from 11 different countries on 4 separate continents, mainly from the United States, Canada, and the United Kingdom. The recruitment rate was 59.9 participants per day, and the conversion rate was 57.2%. Recruitment costs were US $13 per enrolled participant and US $22 per participant completing the study. CONCLUSIONS: It is feasible and rapid to recruit a large number of participants from locations different from the investigator and to retain patients in an observational study with no visits to a clinical site at low costs.

Potential role of CXCR4 in trastuzumab resistance in breast cancer patients.

Despite the efficacy of trastuzumab in treating HER2-positive breast cancer patients, a significant proportion of patients relapse after treatment. The role of C-X-C chemokine receptor type 4 (CXCR4) in trastuzumab resistance was studied only in cell lines and the underlying mechanisms remain largely unclear. This study investigated the role of CXCR4 in trastuzumab resistance in breast cancer patients and explored the possible underlying mechanisms. The study was performed retrospectively on tissue samples from 62 breast cancer patients including 42 who were treated with trastuzumab and chemotherapy and 20 who received chemotherapy alone in adjuvant setting. Expression levels of CXCR4 and its regulators hypoxia-inducible factor 1-alpha (HIF-1α), tristetraprolin (TTP), human antigen R (HuR), itchy E3 ubiquitin protein ligase (ITCH), miR-302a and miR-494 were determined and their associations with tumor recurrence and disease-free survival were analyzed. In trastuzumab-treated patients, high CXCR4 expression was associated with recurrence and was an independent predictor of progression risk after therapy. CXCR4 correlated positively with its transcriptional regulator, HIF-1α, and negatively with its post-translational regulator, ITCH. HIF-1α, HuR and ITCH were significantly associated with clinical outcome. In chemotherapy-treated patients, neither CXCR4 nor any of its regulators were associated with recurrence or predicted disease progression risk after chemotherapy. In conclusion, this study suggests a potential role for CXCR4 in recurrence after trastuzumab-based therapy in human breast cancer that could be mediated, at least in part, by hypoxia and/or decreased ubiquitination. These findings highlight the potential utility of CXCR4 as a promising target for enhancing trastuzumab therapeutic outcome.

Hotspots and development frontiers of circRNA based on bibliometric analysis.

Background and purpose: Circular RNAs (circRNAs) are a big group of members of the noncoding RNA family following long non-coding RNA and microRNA. They play a regulatory role in many biological processes. Analyzing their current research status and future development trends is conducive to a more comprehensive understanding of circRNAs and contributes to the dedication to the biological field. Methods: The literature on circRNA from 2000 to 2021 in the Web of Science Core Collection of the Web of Science database with "circular RNA" as the subject was searched. R Studio's Bibliometrix package and biblioshiny software were used for publication trend analysis, citation analysis, keyword analysis, author analysis, research institution analysis, source analysis, country analysis, and collaboration analysis for all documents and highly cited documents. Results: From 2000 to 2021, 3,186 circRNA-related articles were published worldwide, of which 193 were highly cited. The number of published articles had shown an explosive increase after 2013. These articles were mainly from Chinese research institutions and authors, but the country with the highest average number of citations per year in highly cited documents was Germany. Scientific research institutions came from countries represented by Germany, USA, China, Australia and Canada all had different degrees of cooperation. The theme and key points of the research had evolved over time from expression to the role and mechanism of circRNA in diseases, especially in cancer. CDR1as, circFOXO3, circHIPK3, circITCH, circMTO1, circSMARCA5 and circZNF609 are circRNAs that are mainly studied currently, their studies mainly involve cell biology, biological functions and cancer. The future research direction and trend would still be the application of circRNA in diseases. Conclusion: The basic situation and development trend of circRNA related research we described provide a direction for future research.