The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: To investigate the mechanism of VPS26 effect on osteogenesis and adipogenesis differentiation of rat bone marrow mesenchymal stem cells (BMSC) in high fat environment, and to explore the effect of VPS26 on implants osseointegration of high fat rats and ectopic osteogenesis in nude mice. Methods: BMSC were cultured under normal osteogenic induction (osteogenic group) and high-fat osteogenic induction (high-fat group).High-fat group was transfected with VPS26 enhancer and inhibitor, and the expression levels of osteogenesis related genes and adipogenesis related genes were examined. Osteogenesis and adipogenesis of BMSC were detected by alkaline phosphatase (ALP) staining and oil red O staining after 7 and 14 days of induction.In osteogenic group,the binding of VPS26 to β-catenin was detected by immunofluorescence staining and immunoprecipitation, and dual luciferase reporter assay (TOP Flash) was used to analyze the TOP/FOP ratio. Eighteen male 12-week hyperlipidemic Wista rats (160-200 g) were implanted with implants, and six in each group were injected with VPS26 overexpression lentivirus (LV-VPS26 group), negative control lentivirus (LV-nc group) and saline (blank control group).Micro-CT analysis , HE and oil red O staining were used to evaluate the osseointegration of the implants and lipid droplets formation of the femur samples. Twenty female 6-week nude mice (30-40 g) were divided into five groups and subcutaneously implanted with osteogenic BMSC non-transfected and transfected LV-VPS26, LV-nc, shVPS26, and shscr lentivirus on the back. Samples were used to observe ectopic osteogenesis. Results: The mRNA expression levels of ALP in the high-fat group BMSC after overexpression of VPS26 (1.56±0.09) were significantly higher than those of the negative control (1.01±0.03) (t=10.09, P<0.001), while those of peroxisome proliferator-activated receptor-γ (PPAR-γ) (t=6.44, P<0.001) and fatty acid-binding protein4 (FABP4) (t=10.01, P<0.001) were lower than those of the negative control. Western blotting results showed that compared with the negative control, protein expression of ALP and Runt-related transcription gene 2 was enhanced in the high-fat group BMSC after overexpression of VPS26 while PPAR-γ and FABP4 were inhibited. ALP activity of BMSC in the high-fat group was stronger after overexpression of VPS26, and the formation of lipid droplets was weaker than that in negative control. The results of immunofluorescence, immunoprecipitation and dual luciferase reporter assays showed co-localization and interaction of VPS26 with β-catenin and a significant 43.10% increase in the TOP/FOP ratio (t=-3.17, P=0.034). VPS26 overexpression enhanced osseointegration and decreased the number of lipid droplets in high-fat rat and enhanced ectopic osteogenesis of nude mice. Conclusions: VPS26 activated osteogenesis differentiation and inhibited adipogenic differentiation of BMSCs through Wnt/β-catenin pathway, promoting osseointegration of high-fat rat implants and ectopic osteogenesis of nude mice.

Humans ; Encephalitis

OBJECTIVE: To observe the effect of blistering moxibustion on the expression levels of 5-hydroxytyptamine (5-HT) and its receptors of the colon tissue in the mice with visceral hypersensitivity of irritable bowel syndrome (IBS), so as to explore the effect mechanism of blistering moxibustion in treatment of IBS. METHODS: Forty SPF-grade newborn Kunming mice were randomly divided into a normal group, a model group, an antagonist group and a blistering moxibustion group, 10 mice in each one. Before modeling, the injection with 0.2 mL parachlorophenylalanine (PCPA) was given on the lateral ventricle in the antagonist group. The endorectal glacial acetic acid stimulation combined with tail clipping was used to prepare the model of visceral hypersensitivity of IBS in the model group, the antagonist group and the blistering moxibustion group. After modeling, in the blistering moxibustion group, the intervention with blistering moxibustion was exerted at "Zhongwan" (CV 12), "Tianshu" (ST 25) and "Zusanli" (ST 36), once herbal irritant plaster at each acupoint, for 2 h each time, once a week, consecutively for 3 weeks. Abdominal withdrawal reflex (AWR) score and electromyographic (EMG) amplitude of abdominal muscles were adopted to evaluate the visceral hypersensitivity. HE staining was applied to observe the morphological changes in colon tissue, and immunohistochemistry was to determine the expression levels of 5-HT and its receptors. RESULTS: Compared with the normal group, EMG amplitude of abdominal muscles was increased under 20, 40 mm Hg (1 mm Hg=0.133 kPa) in the model group (P<0.05), AWR scores and EMG amplitude of abdominal muscles under 60, 80 mm Hg were all increased in the model group (P<0.05). In comparison with the model group, EMG amplitude of abdominal muscles was reduced under 20 mm Hg in the blistering moxibustion group (P<0.05), AWR scores were increased under 40 mm Hg in both the blistering moxibustion group and the antagonist group (P<0.05); AWR scores and EMG amplitude of abdominal muscles under 60, 80 mm Hg were all reduced in both the blistering moxibustion group and the antagonist group (P<0.05). Compared with the normal group, in the model group, the mucosa was slightly disturbed, while, the moderate inflammatory cells were visible in the submucosa. In comparison with the model group, the inherent glands of mucosa were regular in shape and a small number of inflammatory cells were visible in both the blistering moxibustion group and the antagonist group. In comparison with the normal group, the average positive staining area percentage (APSAP) of 5-HT and 5-HT₃R of the colon tissue was increased, while, APSAP of 5-HT₄R was reduced in the model group (P<0.05). Compared with the model group, APSAP of 5-HT and 5-HT₃R was reduced in both the blistering moxibustion group and the antagonist group (P<0.05). CONCLUSION Blistering moxibustion can relieve the visceral hypersensitivity of the mice with visceral hypersensitive IBS and the underlying mechanism is related to the regulation of the gut-brain axis mediated by 5-HT signaling pathway.
Animals ; Disease Models, Animal ; Hypersensitivity ; Irritable Bowel Syndrome/therapy* ; Mice ; Moxibustion ; Rats ; Rats, Sprague-Dawley ; Serotonin ; Signal Transduction

Background::Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients’ quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population.Methods::This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria.Results::In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals ( P < 0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals ( P < 0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria. Conclusion::This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.

Animals ; Cdc20 Proteins/metabolism* ; Cell Line ; Embryo, Mammalian/embryology* ; Embryonic Development ; Female ; Infertility, Female/metabolism* ; Mice ; Mutation ; Oocytes/metabolism*

Angiotensin (Ang)-(1-7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1-7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1-7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 expression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1-7) in the PVN, through modulation of PICs and oxidative stress.
Angiotensin I ; antagonists & inhibitors ; metabolism ; Animals ; Antioxidants ; pharmacology ; Blood Pressure ; drug effects ; Hypertension ; chemically induced ; drug therapy ; Male ; Oxidative Stress ; drug effects ; Paraventricular Hypothalamic Nucleus ; drug effects ; Peptide Fragments ; antagonists & inhibitors ; metabolism ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Sodium Chloride, Dietary ; pharmacology

Objective To study the antiviral effect of Jin Qiao Tablets on influenza A H1N1 virus in vivo. Methods The mouse pneumonia model was established by nasal inhalation of 15 LD50 of influenza virus. After prophylactic or therapeutic medication for 5 d,mouse lung tissue was taken out and weighed. Viral load in lung tissue was measured by polymerse chain reaction(PCR),and the level of γ-interferon(γ-IFN)in rat serum and lung was detected by double antibody sandwich enzyme-linked immunosorbent assay (ELISA)for evaluating the effect of Jin Qiao Tablets on lung index, viral load and γ-IFN in rats. After prophylactic or therapeutic medication for 7 d,morbidity and mortality within 14 d of mice with pneumonia induced by nasal inhalation of 3 LD50 were observed to evaluate the action of Jin Qiao Tablets for protecting against death and prolonging life span. Results Jin Qiao Tablets markedly decreased the increased lung index,promoted the death-protection rate and life-prolongation rate, decreased viral load, raised the level of γ-IFN in mice (P < 0.05 or P < 0.01). Experimental results in vivo showed that Jin Qiao Tablets had better anti-influenza virus activity than Yinqiao Jiedu Tablets and Lianhua Qingwen Capsules, and the effect of Jin Qiao Tablets was equivalent to that of Tamiflu. The prophylactic effect of Jin Qiao Tablets was stronger than the therapeutic effect, but there was no significant difference between them. Conclusion Jin Qiao Tablets have obvious effect against influenza A H1N1 virus in vivo.