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This paper aims to explore the anti-inflammatory mechanism of Saracae Cortex by using network pharmacology and molecular docking methods and verify it through the inflammation model of zebrafish. The effective components, potential core targets, and signaling pathways of Saracae Cortex were obtained by using network pharmacology. A lipopolysaccharide(LPS)-induced inflammation model of zebrafish was established to evaluate the anti-inflammatory activity of aqueous extract and 70% ethanol extract of Saracae Cortex with cell apoptosis rate and reactive oxygen species(ROS) production rate as indicators. q PCR was performed to verify the main targets predicted by network pharmacology. The prediction found that there were 121 potential anti-inflammatory targets in Saracae Cortex. Protein-protein interaction(PPI) analysis showed that Saracae Cortex mainly acted on signal transducer and activator of transcription 3(STAT3), vascular endothelial growth factor A( VEGFA), epidermal growth factor( EGF), tumor necrosis factor( TNF),tumor protein p53(TP53), matrix metalloprotein 9(MMP9), c-fos proto-oncogene protein(FOS), estrogen receptor 1(ESR1), cx-c motif chemokine ligand 8(CXCL8), cluster of differentiation 8(CD8), and other targets. Gene Ontology(GO) analysis showed the biological process mainly acted on the inhibition of apoptosis, the positive regulation of gene expression, and the positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that the mitogen-activated protein kinase(MAPK) signaling pathway, PI3K-Akt signaling pathway, and hypoxia-inducible factor 1(HIF-1) signaling pathway may play a key role in anti-inflammation of Saracae Cortex. Molecular docking verified that five key compounds had a strong binding force with their corresponding core target. Zebrafish animal experiments showed that Saracae Cortex could significantly inhibit ROS formation and reduce cell apoptosis in juvenile fish caused by inflammation and inhibit the further enhancement of inflammatory response in tissue. In addition, compared with the blank group, the transcription levels of nuclear factor kappa-B(NF-κB), TP53, FOS, adaptor protein complex-1(AP-1), and mitogen-activated protein kinases P38(P38) were significantly up-regulated in the model group. Compared with the model group, the m RNA expression of NF-κB, TP53, FOS, AP-1, and P38 was significantly down-regulated in zebrafish tissue treated with aqueous extract and 70% ethanol extract of Saracae Cortex. Saracae Cortex plays an anti-inflammatory role through multiple components and targets, and its anti-inflammatory effect may be related to the inhibition of the MAPK signaling pathway.

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An increased need for child and adolescent behavioral health services compounded by a long-standing professional workforce shortage frames our discussion on how behavioral health services can be sustainably delivered and financed. This article provides an overview of different payment models, such as traditional fee-for-service and alternatives like provider salary, global payments, and pay for performance models. It discusses the advantages and drawbacks of each model, emphasizing the need to transition toward value-based care to improve health care quality and control costs.

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BACKGROUND: Clinical practicum is crucial for strengthening nursing students' clinical competence. However, nursing students often experience considerable stress during clinical practicum, and so they employ coping strategies to alleviate it. There is almost no empirical evidence on the change trajectory of perceived stress, coping strategies, and clinical competence among nursing students during a one-year clinical practicum. This study aimed to investigate the trajectory of change in perceived stress, coping strategies, and clinical competence among undergraduate nursing students during a one-year clinical practicum. METHODS: This study used a longitudinal cohort design. Undergraduate nursing students were recruited from a science and technology university in Taiwan to participate from February 2021 to January 2022. Perceived stress, coping strategies, and clinical competence among students in basic training practicum (T1), advanced training practicum (T2), and comprehensive clinical nursing practicum (T3) were surveyed by using the Perceived Stress Scale (PSS), Coping Behaviour Inventory (CBI), and Clinical Competence Scale (CCS). PSS, CBI, and CCS in T1, T2, and T3 were compared using a generalized estimating equation (GEE) to deal with correlated data. The level of statistical significance was set at α = 0.05. RESULTS: A total of 315 undergraduate nursing students completed the questionnaire. The study results show that the overall perceived stress of the students is the highest in T2 and the lowest in T3. The main source of stress of the students is 'taking care of patients' at T1 and 'lack of professional knowledge and skills' at T2 and T3. Students' perceived stress in 'taking care of patients' gradually decreases over time. The four coping strategies of CBI, which are 'stay optimistic', 'problem-solving', 'transference' and 'avoidance' in this order, remain the same ranking in three surveys.The main stress coping strategy used by students is 'stay optimistic', while the coping strategy 'avoidance' is used more frequently in T2 than in T1 and T3. Students' mean scores of the overall clinical competence and in the 'general nursing' and 'management' subscales in T3 are higher than those in T1 and T2. However, their mean scores in 'self-growth' and 'positivity' subscales are the highest in T1 and the lowest in T2. CONCLUSIONS: The results show that through experiential learning in clinical practicum at different stages time after time, students' overall perceived stress is the lowest and their overall clinical competence is the highest in T3. The main coping strategy used when students managed stress is 'stay optimistic'. According to the results, we suggest that clinical educators provide students with appropriate guidance strategies at different stages of stress and continue to follow up the clinical competence and retention rates of these nursing students in the workplace in the future.

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In brief: The proliferation of the endometrium is regulated by histone methylation. This study shows that decreased NSD2 impairs proliferative-phase endometrial stromal cell proliferation in patients with recurrent implantation failure via epigenetic reprogramming of H3K36me2 methylation on the promoter region of MCM7. Abstract: Recurrent implantation failure (RIF) is a formidable challenge in assisted reproductive technology because of its unclear molecular mechanism. Impaired human endometrial stromal cell (HESC) proliferation disrupts the rhythm of the menstrual cycle, resulting in devastating disorders between the embryo and the endometrium. The molecular function of histone methylation enzymes in modulating HESC proliferation remains largely uncharacterized. Herein, we found that the levels of histone methyltransferase nuclear receptor binding SET domain protein 2 (NSD2) and the dimethylation of lysine 36 on histone H3 are decreased significantly in the proliferative-phase endometrium of patients with RIF. Knockdown of NSD2 in an HESC cell line markedly impaired cell proliferation and globally reduced H3K36me2 binding to chromatin, leading to altered expression of many genes. Transcriptomic analyses revealed that cell cycle-related gene sets were downregulated in the endometrium of patients with RIF and in NSD2­knockdown HESCs. Furthermore, RNA-sequencing and CUT&Tag sequencing analysis suggested that NSD2 knockdown reduced the binding of H3K36me2 to the promoter region of cell cycle marker gene MCM7 (encoding minichromosome maintenance complex component 7) and downregulated its expression. The interaction of H3K36me2 with the MCM7 promoter was verified using chromatin immunoprecipitation-quantitative real-time PCR. Our results demonstrated a unifying epigenome-scale mechanism by which decreased NSD2 impairs endometrial stromal cell proliferation in the proliferative-phase endometrium of patients with RIF.

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Feline coronavirus (FCoV) is the causative agent of feline infectious peritonitis and diarrhoea in kittens worldwide. In this study, a total of 73 feline diarrhoeal faecal samples were collected from animal hospitals and pet markets in ShanDong province from 2017 to 2019. FCoV was detected in 58.23% (46/73) of the samples, using the RT-PCR method. The results showed that the detection rate of FCoV in healthy cats and sick cats was 41.7% (10/24) and 81.6% (40/49), respectively. Full gene amplification and sequencing of the N, M, and S2 genes of FCoV isolates were performed. An amino acid mutation (M1058L) in the S2 gene was found that can be used as a marker for distinguishing feline enteric coronavirus (FECV) from feline infectious peritonitis virus (FIPV). This study provides new epidemiological information about FCoV that will aid in the prevention of FCoV in China.

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An ICU is a critical care unit that provides advanced medical support and continuous monitoring for patients with severe illnesses or injuries. Predicting the mortality rate of ICU patients can not only improve patient outcomes, but also optimize resource allocation. Many studies have attempted to create scoring systems and models that predict the mortality of ICU patients using large amounts of structured clinical data. However, unstructured clinical data recorded during patient admission, such as notes made by physicians, is often overlooked. This study used the MIMIC-III database to predict mortality in ICU patients. In the first part of the study, only eight structured variables were used, including the six basic vital signs, the GCS, and the patient's age at admission. In the second part, unstructured predictor variables were extracted from the initial diagnosis made by physicians when the patients were admitted to the hospital and analyzed using Latent Dirichlet Allocation techniques. The structured and unstructured data were combined using machine learning methods to create a mortality risk prediction model for ICU patients. The results showed that combining structured and unstructured data improved the accuracy of the prediction of clinical outcomes in ICU patients over time. The model achieved an AUROC of 0.88, indicating accurate prediction of patient vital status. Additionally, the model was able to predict patient clinical outcomes over time, successfully identifying important variables. This study demonstrated that a small number of easily collectible structured variables, combined with unstructured data and analyzed using LDA topic modeling, can significantly improve the predictive performance of a mortality risk prediction model for ICU patients. These results suggest that initial clinical observations and diagnoses of ICU patients contain valuable information that can aid ICU medical and nursing staff in making important clinical decisions.

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In 2019, the University of California at San Francisco (UCSF) launched the Child and Adolescent Psychiatry Portal (CAPP), a pediatric mental health care access (PMHCA) program providing remote mental health consultation services to pediatric primary care providers (PCPs) throughout Northern and Central California. The development and implementation of CAPP was guided by Human-Centered Design (HCD), an iterative, rapid-paced innovation process focusing on stakeholders' needs and experiences, which shaped the development of CAPP's programs. The resulting key programmatic elements are designed for pediatric workforce development: (1) PCP consultation with a child and adolescent psychiatrist via a telephone warmline; and (2) training and education for providers. CAPP has grown rapidly since its launch, having enrolled 1,714 providers from 257 practices spread across 36 counties and provided 3,288 consults on 2,703 unique lives as of August 2023. Preliminary evaluation findings indicate high PCP satisfaction with CAPP's services, despite continued challenges of integrating behavioral health into primary care. Throughout the HCD and implementation process, multidisciplinary partnerships have proven critical in providing end-user input to inform and improve program design. This growing network of partnerships, developed through the cultivation of personal relationships and trust over time, has also proven essential for CAPP's rapid growth and sustainability. Overall, this Community Case Study highlights the critical role of partnerships and the importance of taking a people-centered approach, as captured in CAPP's motto, "Connecting for Care."

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Objective: There has been an increase in Child Psychiatry Access Programs (CPAP) across the United States to address the national child and adolescent psychiatry workforce shortage by supporting pediatric primary care providers (PCPs) in providing mental health services. The objective of this systematic review is to synthesize the expanding literature on CPAPs. Method: A systematic literature search was conducted in PubMed, PsycInfo, Embase, and Web of Science databases to identify articles published from database inception to April 6, 2022, to identify CPAPs, defined as programs with mental health specialists providing rapid remote mental health consultation services to pediatric PCPs. Study outcomes included program adoption, provider experience, patient and caregiver experience, program cost, and patient mental health. Results: None of the 33 included studies were randomized controlled trials. Most of the studies (n = 30) focused on program adoption and provider experience (n = 18). Few studies examined patient and caregiver experience (n = 2), program cost(n = 4), or patient mental health (n = 4) outcomes. CPAPs showed year-over-year growth in adoption and were generally well-received by providers and caregivers. Health care provision costs were quite varied. No articles reported on changes in patient mental health according to validated measures. Heterogeneity in the methodological quality, study design, and outcomes used to evaluate CPAPs hindered comparison among programs. Conclusion: Rigorous research on the impact of CPAPs is lacking. Findings show high provider satisfaction with CPAPs, yet few studies examine patient-level mental health outcomes. CPAPs and funding agencies should consider prioritizing and investing in research to build the evidence base for CPAPs. Diversity & Inclusion Statement: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. Clinical trial registration information: Child Psychiatry Access Programs: A Systematic Review; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020146410; CRD42020146410.

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Due to a national shortage of child and adolescent psychiatrists, pediatric primary care providers (PCPs) are often responsible for the screening, evaluation, and treatment of mental health disorders. COVID-19 pandemic stay-at-home orders decreased access to mental health care and increased behavioral and emotional difficulties in children and adolescents. Despite increased demand upon clinicians, little is known about mental health care delivery in the pediatric primary care setting during the pandemic. This focus group study explored the experiences of pediatric PCPs and clinical staff delivering mental health care during the pandemic. Transcripts from nine focus groups with San Francisco Bay Area primary care practices between April and August 2020 were analyzed using a thematic analysis approach. Providers expressed challenges at the patient-, provider-, and system-levels. Many providers reported increased patient mental health symptomatology during the pandemic, which was often intertwined with patients' social determinants of health. Clinicians discussed the burden of the pandemic their own wellness, and how the rapid shift to telehealth primary care and mental health services seemed to hinder the availability and effectiveness of many resources. The findings from this study can inform the creation of new supports for PCPs and clinical staff providing mental health care.

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BACKGROUND: Restless legs syndrome (RLS), a neurological disorder, often affects sleep quality in hemodialysis patients. This study aimed to evaluate acupressure's effect on the severity of RLS symptoms and sleep quality in hemodialysis patients with RLS. METHODS: This study is a cluster-randomized crossover pilot study. Patients were randomized to two sequences: acupressure for one month and observation for another month (AC); and observation for one month and acupressure for another month (CA). For the four-week acupressure intervention, patients received 36 min of acupressure three times weekly during their hemodialysis sessions. The acupoints were on the bilateral lower limbs, including Zusanli (ST36), Yanglingquan (GB34), Sanyinjiao (SP6), Xuanzhong (GB39), Chengshan (BL57), and Taichong (LR3). RLS severity and sleep quality (measured with the Pittsburgh sleep quality index, PSQI) were measured at baseline, month 1, and month 2. RESULTS: AC sequence (n = 14) was similar to the CA sequence (n = 9) in terms of gender, age, education, employment, marital status, comorbid disease, BMI, duration of dialysis, medication for RLS and insomnia, RLS severity, and PSQI. The general linear mixed model revealed no significant carryover effect on RLS severity, PSQI, and the seven subscales of PSQI. A significant treatment effect (acupressure) was only observed in RLS severity (p = 0.0013) but not in PSQI and the seven subscales. The significant period effect was observed in RLS severity (p = 0.0250) and the subscale of sleep disturbance (p = 0.0021). CONCLUSION: In hemodialysis patients with RLS, acupressure can alleviate the severity of RLS but cannot improve sleep quality.

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BACKGROUD: BolA gene family contains three members, high expression of BolA family member 2 (BOLA2) has been reported to be associated with prognosis of several cancers. However, the relationship between BOLA3 and lung adenocarcinoma (LUAD) remains unclear. METHODS: Expression of BOLA3 was analyzed by online database. Co-expressed genes and gene set enrichment analysis (GSEA) were performed using LinkedOmics. Diagnostic value was assessed using receiver operating characteristic (ROC) curves. The prognostic value of BOLA3 was analyzed using Prognoscan and Kaplan-Meier Plotter. The Tumor Immune Estimation Resource (TIMER) and Single-sample Gene Set Enrichment Analysis (ssGSEA) were used to explore the relationship between BOLA3 and tumor immune infiltration. RESULTS: The results showed that the expression of BOLA3 was significantly higher in LUAD than in normal tissues. High expression of BOLA3 was associated with T stage, N stage, pathologic stage (all P < 0.001). In addition, elevated expression of BOLA3 was associated with overall survival (OS) and progression-free survival (PFS) in LUAD ((OS:HR = 2.58, log-rank P = 1.3e - 11; PFS:HR = 2.36, log-rank P = 4.1e - 05). BOLA3 expression level has negative correlations with infiltrating levels of B cells, CD4 +T cells, macrophages, neutrophils, and dendritic cells (DCs). GSEA analysis showed BOLA3 joined mainly in mitochondrial respiratory chain complex assembly, translational initiation, etc. CONCLUSIONS: These results showed up-regulated in BOLA3 was correlated with poor prognosis and immune infiltrates in LUAD, BOLA3 can be served as a potential immunotherapy target.

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Recurrent pregnancy loss (RPL) is a multifactorial condition with no explanation of miscarriage in approximately half of the RPL patients, consequently leaving deep physical and emotional sequels. Transcription factor 3 (TCF3 or E2A), is a unique member of the LEF/TCF family and plays an important role in embryogenesis. However, its function in RPL is poorly understood. Using real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry, we demonstrated that TCF3 was downregulated in decidual tissues from RPL patients compared with healthy control (HC). Further, TCF3 knockdown inhibited proliferation, induced G0/G1 phase arrest, and promoted migration in human endometrial stromal cells (HESCs), while overexpression of TCF3 exhibited the opposite effects. RNA-sequencing analysis combined with gene-set enrichment analysis results showed that the mitogen-activated protein kinase pathway is potentially downstream of TCF3. Knockdown of TCF3 confirmed increased p38 phosphorylation, while overexpression of TCF3 inhibited p38 phosphorylation. Furthermore, we found that TCF3 protein level was decreased in HESCs under hypoxic incubation, while hypoxia-inducible factor-1α (HIF1A) knockdown increased the expression of TCF3. TCF3 overexpression recovered the proliferation ability of HESCs inhibited by hypoxia and reversed hypoxia-induced migration. Consistently, we found that RPL patients had a significantly higher level of HIF1A in the decidual tissue than HC. Overall, this study clarifies that increased HIF1A in the decidua contributes to the occurrence of RPL through the TCF3/p38 signaling pathway.

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@#AIM: To evaluate the application effect of limbal stem cell transplantation fixed by corneal bandage lens with no suture method in primary pterygium excision surgery.<p>METHODS:Selected 25 patients of 50 eyes with bilateral primary pterygium who were admitted into our hospital from January 2019 to December 2019 for prospective clinical study. Group A(25 eyes)were randomly chosen with one eye of a patient fixed with corneal bandage lens with no suture; and Group B(25 eyes)were chosen with the other eye of a patient using traditional suture method. The incision healing, patient comfort, surgical complications, and postoperative recurrence were observed in both groups after postoperative follow-up for 6mo.<p>RESULTS: The average operating time for Group A(13.5±2.1min)was significantly less than that of Group B(26.6±7.2min). The results of postoperative follow-up in 1d, 1, 2wk, 1, 3 to 6mo showed that the discomfort such as pain, photophobia, lacrimation, foreign body sensation and itching were lower in Group A than in Group B. The discomfort disappeared in both groups after 6mo. The stability of postoperative corneal rim stem cell transplants was favorable in Group A, and the complications one and three months after surgery were less than those in Group B.<p>CONCLUSION: The method of banded corneal rim stem cell conjunctival transplantation combined with corneal bandage lens is an effective procedure for the treatment of primary pterygium. It is simple, convenient, safe and effective, the postoperative comfort is good, the recurrence rate is low, compared with the traditional suture method, it can shorten the operation time and effectively reduce the patient's pains.

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Adolescence is the time of onset of many psychiatric disorders. Half of pediatric patients present with comorbid psychiatric disorders that complicate both their medical and psychiatric care. Currently, diagnosis and treatment decisions are based on symptoms. The field urgently needs brain-based diagnosis and personalized care. Neuroimaging can shed light on how aberrations in brain circuits might underlie psychiatric disorders and their development in adolescents. In this perspective article, we summarize recent MRI literature that provides insights into development of psychiatric disorders in adolescents. We specifically focus on studies of brain structural and functional connectivity. Ninety-six included studies demonstrate the potential of MRI to assess psychiatrically relevant constructs, diagnose psychiatric disorders, predict their development or predict response to treatment. Limitations of the included studies are discussed, and recommendations for future research are offered. We also present a vision for the role that neuroimaging may play in pediatrics and primary care in the future: a routine neuropsychological and neuropsychiatric imaging (NPPI) protocol for adolescent patients, which would include a 30-min brain scan, a quality control and safety read of the scan, followed by computer-based calculation of the structural and functional brain network metrics that can be compared to the normative data by the pediatrician. We also perform a cost-benefit analysis to support this vision and provide a roadmap of the steps required for this vision to be implemented.

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Atherosclerosis is characterized, as an inflammatory disorder in the circulatory system, with increasing tendency toward mortality and morbidity. Thus, developing novel therapeutic targeting inflammation is necessary. Here, we investigated the effects of interleukin-36 receptor antagonist (IL-36RN), a newly identified anti-inflammatory factor, on atherosclerosis. The regulation of NLRP3 inflammasome by IL-36RN was determined in vitro in macrophage cells after oxidized low-density lipoprotein (ox-LDL) stimulation. The IL-1ß and caspase-1 p10 secretion were assessed by enzyme-linked immunosorbent assay and western blot analysis. Finally, the IL-36RN/NLRP3 inflammasome pathway was confirmed in apolipoprotein E-deficient mice. IL-36RN suppressed the expression of NLRP3, the secretion of IL-1ß, and caspase-1 p10 in vitro, while IL-36 pathway stimulation activated the NLRP3 inflammasome, which was inhibited by IL-36RN. In the mouse model of atherosclerosis, IL-36RN delivered by the lentivirus vector inhibited the development of atherosclerosis, and the atheroprotective effects of IL-36RN were attenuated by IL-36 pathway stimulation. Furthermore, the regulation of NLRP3 inflammasome by IL-36RN was also confirmed in vivo. We demonstrated here that IL-36RN exerted atheroprotective functions through IL-36RN/NLRP3 inflammasome pathway.

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The coronavirus disease 2019 pandemic caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has claimed many lives worldwide. Wearing medical masks (MMs) or N95 masks ([N95Ms] namely N95 respirators) can slow the virus spread and reduce the infection risk. Reuse of these masks can minimize waste, protect the environment, and help solve the current imminent shortage of masks. Disinfection of used masks is needed for their reuse with safety, but improper decontamination can damage the blocking structure of masks. In this study, we demonstrated using the avian coronavirus of infectious bronchitis virus to mimic SARS-CoV-2 that MMs and N95Ms retained their blocking efficacy even after being steamed on boiling water for 2 hours. We also demonstrated that three brands of MMs blocked over 99% viruses in aerosols. The avian coronavirus was completely inactivated after being steamed for 5 minutes. Altogether, this study suggested that MMs are adequate for use on most social occasions and both MMs and N95Ms can be reused for a few days with steam decontamination between use.

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Importance: Emerging evidence suggests that integrated care models are associated with improved mental health care access and outcomes for youths (children ≤12 years and adolescents 12-21 years) served in pediatric primary care settings. However, the key components of these complex models remain unexamined. Objective: To identify and describe the key components of effective pediatric integrated mental health care models. Evidence Review: The PubMed, Embase, PsycINFO, and Cochrane Controlled Register of Trials electronic databases were searched for relevant peer-reviewed articles published between January 1, 1985, and April 30, 2019. Articles were restricted to those published in the English language. Eligible articles reported original data on youths 17 years or younger, implemented an integrated mental health care model in a pediatric primary care setting, and assessed the model's association with primary outcomes (eg, mental health symptom severity) and secondary outcomes (eg, functional impairment and patient satisfaction). Articles that specified some degree of systematic coordination or collaboration between primary care and mental health professionals were included in the final review. Two independent reviewers extracted data on study design, model type, model components, level of integration, and outcomes. Study quality was assessed using the Jadad scale. Data were analyzed between January 1, 2018, and May 31, 2019. Findings: Eleven randomized clinical trials involving 2190 participants were included. Three studies focused on youths with depression, 3 on youths with attention-deficit/hyperactivity disorder, and 5 on youths with behavioral disorders. Most studies (9 of 11) implemented either the collaborative care model (n = 3), a slightly modified version of the collaborative care model (n = 2), or colocated care (n = 4). The most commonly reported components of effective pediatric integrated mental health care models were population-based care, measurement-based care, and delivery of evidence-based mental health services; all 3 components were present in studies reporting clinical improvement of mental health symptoms. Other model components, such as treatment-to-target or team-based care, were common in studies reporting specific outcomes, such as functional impairment. Conclusions and Relevance: This review is the first to date to systematically search and qualitatively synthesize information on the key components of effective pediatric integrated mental health care models. This knowledge may be especially useful for pediatric primary care administrators in the selection of an integrated care model for their setting.

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Current studies have shown that circular RNAs (circRNAs) and microRNAs (miRNAs) are closely related in acute myocardial infarction (AMI). Previous studies have shown that miR-125b promotes fibrosis and up-regulates in cardiac fibroblasts (CFs), and further experiments showed that circ_LAS1L had multiple binding sites of miR-125b, and their expression was inversely related in AMI patients and CFs. RNA immunoprecipitation (RIP), pull down, and dual luciferase reporter gene assay all confirmed that miR-125b directly bound to circ_LAS1L. Circ_LAS1L overexpression promoted the expression of downstream target gene secreted frizzled-related protein 5 (SFRP5), inhibited the expression of alpha-SMA, collagen I, and collagen III, inhibited CF proliferation and migration, and promoted apoptosis. When cotransfected with circ_LAS1L overexpression vector and miR-125b mimics, the above gene expression and CF biological behaviours did not change significantly. But when cotransfected with circ_LAS1L overexpression vector and SFRP5 siRNA, SFRP5 expression was still down-regulated, the expression of alpha-SMA, collagen I, and collagen III was up-regulated, and the proliferation and migration of CFs were increased. Therefore, circ_LAS1L inhibits the activity of miR-125b by adsorbing it, thus promoting the expression of SFRP5 and then regulating the biological characteristics of CFs. These findings may provide an important experimental basis for the regulation of myocardial fibrosis after myocardial infarction. SIGNIFICANCE OF THE STUDY: Studies have shown that circular RNAs (circRNAs) play important roles in cardiovascular diseases, but there are few studies on their roles in the process of myocardial fibrosis. In this study, we found that circ_LAS1L was down-regulated in acute myocardial infarction (AMI) patients and cardiac fibroblasts (CFs), and could bind directly to miR-125b, thereby promoting the expression of downstream target gene secreted frizzled-related protein 5 (SFRP5), ultimately inhibiting the activation, proliferation and migration of CF, and promoting apoptosis. This suggests that circ_LAS1L/miR-125b/SFRP5 pathway can regulate the biological function of CF and may play an important role in the process of myocardial fibrosis, thus providing an important theoretical basis for the regulation of myocardial fibrosis after myocardial infarction.

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Acute alcohol intoxication is responsible for a sizable share of emergency department visits. Intoxicated individuals without other medical needs may not require the high level of care provided by an emergency department. We estimate the impact on U.S. health care spending if individuals with uncomplicated, acute alcohol intoxication were treated in sobering centers instead of the emergency department. We performed a budget impact analysis from the perspective of the U.S. health care system based on published and gray literature reports. Ninety-five percent confidence intervals (CI) were estimated using Monte Carlo modeling with random variation for three variables (cost of an emergency department visit, cost of a sobering center visit, and start-up costs per sobering center visit) and the percentage of cases diverted from emergency departments to sobering centers. Outcomes were expressed in terms of national savings in 2017 U.S. dollars. Assuming a diversion rate of 50% based on previous studies, national savings range from $230 million to $1.0 billion annually. In the Monte Carlo modeling, we found annual national savings of $99.02 million (95% CI: $95.89-$102.19 million), $792.34 million (95% CI: $767.09-$817.58 million), and $1,185.51 million (95% CI: $1,150.64-$1,226.37 million) with diversion rates of 5%, 40%, and 60%, respectively. Implementing sobering centers as a treatment alternative for individuals with uncomplicated acute alcohol intoxication could yield substantial cost savings for the U.S. health care system.

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