Sepsis is a life-threatening organ dysfunction caused by the host's dysregulated response to infection, with a complex pathogenesis and high mortality rate. Currently, there are no clear and effective treatment drugs available. Epigenetic modification serves as a major mechanism regulating gene expression under pathological and physiological conditions, and it has been shown to play a critical role in regulating the occurrence and development of sepsis. Histone acetylation modification, as a sophisticated epigenetic modification mechanism, plays a crucial regulatory role in many aspects of life. It can jointly regulate the acetylation status of histones through histone acetyltransferase (HAT) and histone deacetylase (HDAC), thereby changing DNA expression and dynamically regulating sepsis related gene expression at the epigenetic level. Previous studies have shown that histone acetylation can participate in the progression of sepsis by regulating inflammatory mediators, nuclear factor-ΚB (NF-ΚB) signaling pathway, autophagy, efferocytosis, ferroptosis, pyroptosis. These mechanisms are promising targets for novel sepsis treatments. In addition, with the deepening of research, it has been found that various selective/non selective histone deacetylase inhibitors (HDACI) can regulate histone acetylation status by acting on different HDAC targets, which has been shown to alleviate organ damage caused by sepsis and improve prognosis in septic animal models. This article further summarizes the role and potential applications of histone acetylation in sepsis, providing new ideas for the treatment of sepsis.
Sepsis/metabolism* ; Acetylation ; Humans ; Histones/metabolism* ; Histone Acetyltransferases/metabolism* ; Histone Deacetylase Inhibitors ; Epigenesis, Genetic ; Histone Deacetylases/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Animals

Pyroptosis is a programmed death of inflammatory cells triggered by pathogen invasion,dependent on caspase activation,through both classical and non-classical pyroptosis pathways.Cell pyroptosis is related to the occurrence and development of a variety of animal infectious diseases caused by microbial infection.After microorganisms invading,cells are stimulated by pathology-re-lated molecular patterns,causing strong immune response,stimulating inflammatory signaling pathways,and then activating inflammasome,leading to pyroptosis.The immune system has e-volved multiple mechanisms to fight microbial infections and regulate inflammatory responses.The innate immune system,by recognizing microbial molecules in pathogens and responding quickly by producing inflammasome and activating pyroptosis,helps clear pathogens to prevent infection and maintain the normal functioning of the body.A thorough study of the pathogenesis and immune es-cape mechanism of cell pyroptosis in animal infectious diseases will provide a new direction for the treatment of animal infectious diseases.

Cardiac arrest most commonly occurs outside of the hospital, known as out-of-hospital cardiac arrest (OHCA), and is an important global health problem. Approximately 40% of cardiac arrest has no clear cause. Hereditary arrhythmias and cardiomyopathies factors contribute to cardiac arrest. The identification of genetic factors for cardiac arrest after its occurrence is of great value not only for the individual, but also for relatives who may be at risk for the disease in their family. In the United States, there are over 350?000 cases of OHCA and over 200?000 cases of in-hospital cardiac arrest (IHCA) each year, and in Western Europe, cardiac arrest accounts for 15%-20% of all adult natural deaths and 50% of all cardiovascular deaths. In order to reduce the burden caused by cardiac arrest within society, it is essential to further understand its etiological factors, such as incidence in different regions, risk factors, and populations at higher risk. For each individual, cardiac arrest is the result of a complex interaction of genetic and acquired factors. Understanding the complex interplay of pathogenic factors in cardiac arrest and the development of individualized prevention and treatment approaches requires the collection of clinical data from cardiac arrest populations and multimodal analysis in order to identify epidemiological features and risk factors for cardiac arrest. Recently, cardiac arrest-related data are being collected and integrated in Europe in different regions and populations. As a result of the commitment to the creation of large datasets of clinical information on cardiac arrest populations, the knowledge of the pathology of cardiac arrest pathogenesis as well as risk factors is steadily increasing. This article reviews the epidemiologic data of cardiac arrest in recent years and the associated risk factors, thus providing ideas for developing better strategies for the prevention and treatment of cardiac arrest.

Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease. Anti-fibrosis treatment is a significant therapy for heart disease, but there is still no thorough understanding of fibrotic mechanisms. This study was carried out to ascertain the functions of cytokine receptor-like factor 1 (CRLF1) in cardiac fibrosis and clarify its regulatory mechanisms. We found that CRLF1 was expressed predominantly in cardiac fibroblasts. Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction, but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-‍β1 (TGF‍-‍β1). Gain- and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. CRLF1 overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of CRLF1 had the opposite effects. An inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and different inhibitors of TGF-‍β1 signaling cascades, comprising mothers against decapentaplegic homolog (SMAD)‍-dependent and SMAD-independent pathways, were applied to investigate the mechanisms involved. CRLF1 exerted its functions by activating the ERK1/2 signaling pathway. Furthermore, the SMAD-dependent pathway, not the SMAD-independent pathway, was responsible for CRLF1 up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression. CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway. CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.
Animals ; Humans ; Mice ; Disease Models, Animal ; Fibroblasts/metabolism* ; Fibrosis ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 3/metabolism* ; Myocardial Infarction/metabolism* ; Receptors, Cytokine/metabolism* ; Signal Transduction ; Transforming Growth Factor beta1/pharmacology*

Objective:To investigate the current situation and influencing factors of patients′ satisfaction with nursing humanistic care, and to provide reference for improving the quality of such care provided by hospitals.Methods:From July to August 2022, outpatients and inpatients in 30 provinces were selected by multi-stage stratified sampling as the survey objects. A cross-sectional survey was conducted on an online platform, using the general information questionnaire and Chinese version of methodist health care system nurse caring instrument revised by the research group. The latter instrument consists of 12 dimensions. namely care coordination, competence, teaching/learning, emotional support, respect for individuality, physical comfort, availability, helping/trusting relationship, patient/family engagement, physical environment, spiritual environment and outcomes. Descriptive analysis was performed on the data collected by the questionnaires, and independent sample t-test and one-way ANOVA were used to analyze the influencing factors of patient satisfaction. Results:A total of 107 hospitals were selected for questionnaire survey, including 86 tertiary hospitals and 21 secondary hospitals, and 29 108 valid questionnaires were recovered. The patient satisfaction with nursing humanistic care scored (5.40±0.86); the top three dimensions were competence (5.50±0.89), emotional support (5.47±0.88) and helping/trusting relationship (5.46±0.86); the lowest scoring dimensions were teaching/learning (5.38±1.01), spiritual environment (5.36±1.04) and patient/family engagement (5.11±1.28). Differences with gender, age, marital status, child status, educational level, occupation, place of residence, economic region, per capita monthly income of the family, type of medical insurance, medical department visited and surgery or not presented significant differences on the patient satisfaction with nursing humanistic care scores ( P<0.05). Conclusions:The satisfaction of patients with hospital′s nursing humanistic care in China was at the middle to upper level. In the future, health education for patients should be strengthened, and a mode of family-engaged nursing humanistic care should be constructed in line with the Chinese cultural background. In the process of nursing services, the particularity of patient groups should be considered to better meet their needs.

Intestinal flora plays an important role in maintaining the body's immune balance, digestion, and nutrient absorption. Thyroid function mainly includes the synthesis and secretion of thyroid hormones and the regulation of metabolic balance in the body. When the body’s thyroid hormone synthesis and secretion are too little or too much, it will lead to thyroid diseases. Studies have shown that intestinal flora may affect the occurrence and development of thyroid diseases by participating in thyroid metabolism, immune regulation, cross immunoreaction, and interaction with thyroid-related predisposing factors. Understanding the structural changes and functional mechanisms of intestinal flora during the occurrence and development of thyroid diseases can provide a new basis for the diagnosis and treatment of thyroid diseases and improvement of clinical prognosis.

Objective:To explore the impact of PM 2.5 concentration in Shanghai on the incidence of allergic rhinitis（AR） in the population, and provide strategies for early warning and prevention of AR. Methods:Collect daily average concentrations of atmospheric pollutants monitored in Shanghai from January 1, 2017 to December 31, 2019, and clinical data of AR patients from five hospitals in Shanghai during the same period. We used a time-series analysis additive Poisson regression model to analyze the correlation between PM 2.5 levels and outpatient attendance for AR patients. Results:During the study period, a total of 56 500 AR patients were included, and the daily average concentration of PM 2.5 was（35.28±23.07）μg/m³. There is a correlation between the concentration of PM 2.5 and the number of outpatient attendance for AR cases. There is a positive correlation between the daily average number of outpatient for AR and levels of PM 2.5 air pollution（（P<0.05）） . We found that every 10 μg/m³ increase in PM 2.5, the impact of on the number of AR visits was statistically significant on the same day, the first day behind, and the second day behind, with the strongest impact being the exposure on the same day. Every 10 μg/m³ increases in PM 2.5, the number of outpatient visits increased by 0.526% on the same day（95%CI 1.000 50-1.010 04）. Conclusion:The atmospheric PM 2.5 concentration in Shanghai is positively correlated with the number of outpatient for AR, and PM 2.5 exposure is an independent factor in the onset of AR. This provides an important theoretical basis for AR.
Humans ; Particulate Matter/analysis* ; Air Pollutants/adverse effects* ; Incidence ; China/epidemiology* ; Air Pollution/adverse effects* ; Rhinitis, Allergic/etiology*

Humans ; Melanoma/therapy* ; Immunotherapy ; Syndrome ; Skin Neoplasms

Melanoma accounts for a small proportion of skin cancers diagnosed each year, but it has a high degree of malignancy and rapid progression, resulting in a short survival period for patients. The incidence of melanoma continues to rise, and now melanoma accounts for 1.7% of cancer diagnoses worldwide and is the fifth most common cancer in the United States. With the development of high-throughput sequencing technologies, the understanding of the pathophysiology of melanoma had also been improved. The most common activating mutations in melanoma cells are BRAF , NRAS , and KIT mutations, which disrupt cell signaling pathways related to tumor proliferation. The progress has led to the emergence of molecularly targeted drugs, which extends the survival of patients with advanced melanoma. A large number of clinical trials have been conducted to confirm that targeted therapy for patients with advanced melanoma can improve progression-free survival and overall survival, and for stage III patients after radical tumor resection targeted therapy can reduce the recurrence of melanoma. Patients who were originally stage III or IV inoperable have the opportunity to achieve tumor radical resection after targeted therapy. This article reviewed the clinical trial data and summarized the clinical benefits and limitations of these therapies.
Humans ; United States ; Melanoma/genetics* ; Skin Neoplasms/pathology* ; Mutation ; Proto-Oncogene Proteins B-raf/therapeutic use*

Objective:To investigate the effects of ursolic acid (UA) on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure.Methods:Sixty healthy female SD rats were randomly divided into five groups: normal control group (NC group), PM2.5 unexposed AR group (AR group), PM2.5 exposed AR group (ARE group), UA intervention AR group (AR+UA group), and UA intervention PM2.5 exposed AR group (ARE+UA group), with 12 rats in each group. AR model was performed by a basal sensitization with intraperitoneal injection of ovalbumin (OVA) and followed by nasal instillation. PM2.5 exposure was carried out by inhalation exposure system at a concentration of 200 μg/m 3 for 3 h/d for 30 days. UA intervention group was given UA intragastric administration at 20 mg/(kg·d). AR symptoms including sneezing, nasal scratching and nasal secretion of rats in each group were observed. The activities of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in nasal mucosa were tested. The pathological changes of nasal mucosa were observed by HE staining. The levels of OVA-sIgE, IL-6 and IL-17 in serum were measured by enzyme-linked immunosorbent assay (ELISA). Protein microarray was used to measure the expression of multiple inflammation cell factors in nasal mucosa. Statistical analysis was performed with SPSS 20.0. Results:After UA intervention, the frequency of nasal sneezing, scratching and nasal secretion in ARE+UA group were lower than those of ARE group ( P<0.05). Pathological examination of nasal mucosa showed that ARE+UA group had less inflammatory granulocyte infiltration and less pathological damage to the epithelial layer than ARE group. The activities of SOD in nasal mucosa of ARE+UA group were higher than those of ARE group ((50.10±3.09) U/mg vs (20.13±1.30) U/mg, F value was 597.54, P<0.01). The contents of MDA in nasal mucosa of ARE+UA group were lower than those of ARE group ((57.78±12.36) nmol/g vs (124.12±9.40) nmol/g, F value was 115.51, P<0.01). The expression levels of OVA-sIgE, IL-6 and IL-17 proteins were lower in the ARE+UA group than those in ARE group ((11.61±0.27) ng/ml vs (20.30±0.67) ng/ml, (47.59±15.49) pg/ml vs (98.83±10.98) pg/ml, (623.30±8.75) pg/ml vs (913.32±9.06) pg/ml, F value was 283.42, 80.45, 683.73, respectively, all P<0.01). After UA intervention, protein microarray analysis showed that the expression of IL-4, IL-6, IL-13, chemokine CXCL7, IL-1α, IL-1β, MMP-8 and MCP-1 in ARE+UA group was decreased compared with ARE group while IFN-γ and IL-10 increased (all P<0.01). Conclusion:UA can reduce the aggravated AR symptoms and pathological damage of nasal mucosa, inhibit oxidative stress and release of inflammatory factors after PM2.5 exposure, and thus plays a protective role in the pathological damage of AR induced by PM2.5 exposure.