Sialoadhesin, also known as CD169, is an adhesion and endocytic receptor of macrophages that can recognize sialic acid. CD169 is a highly conservative molecule in evolution. Under physiological conditions, CD169 is expressed on the surface of macrophage subpopulations in secondary lymphoid tissues. Several studies have demonstrated that CD169⁺ macrophages can phagocytize pathogens by interacting with α2,3- and α2,6-sialic proteins, and can also coordinate with DC to cross-present antigens to T cells. Moreover, CD169 can exert an immunosuppression role by inhibiting the expression of type Ⅰ IFN in macrophages. Recently, the roles of CD169⁺ macrophages in various pathological conditions have been reported. It has been shown that when erythropoiesis is under stress, CD169⁺ macrophages can bind to CD43 of erythroblast and affect erythroblast differentiation. In addition, CD169 has been reported to play a dual role during pathogen infection or tumor progression. This review will focus on the advance progress of CD169 and the function of CD169⁺ macrophage, as well as its role in various diseases including virus infection, tumor development, and hematological diseases.

B cells are the major component in the tumor microenvironment and play key roles in tumor immunity. Previous studies have suggested that B cells promote tumor progression via secreting immune-inhibitory cytokines or activating the complement system through  B cell-secreted antibodies. However, recent studies have revealed an important role of B cells in anti-tumor immune responses. This review summarizes the multiple functions of B cells in tumor immunity and discusses the underlying mechanisms and the effects on patients prognosis. 

Medulloblastoma (MB) is the most common pediatric brain malignancy, with a 5-year overall survival (OS) rate of around 70%. In recent years, the role of the tumor microenvironment on tumor growth has attracted extensive attention. The interaction between tumor cells and other cells in the tumor microenvironment including tumor-associated macrophages (TAM), T cells, NK cells, B cells, and tumor-associated astrocytes (TAA) plays an important role in the onset and progression of MB. Understanding the tumor immune microenvironment of this tumor, especially the relationship between tumor and immune cells, is crucial for the effective development of immune-based therapeutic strategies for MB. This review summarizes the latest research progress on the tumor microenvironment and immunotherapy of MB.

To investigate the mechanism by which salidroside improves keloid on regulating JAG1/Notch3 signaling pathway through miR-26a-5p, 10 keloid patients diagnosed by histopathology in Wuhan Hospital of Traditional Chinese Medicine were enrolled as the research objects from October 2019 to January 2021. The keloid tissues removed by surgery were used in the keloid group, and the adjacent healthy skin tissues were used in the normal group. Primary keloid fibroblasts were isolated and cultured, and the cells of generation 4~8 were divided into 8 groups: control group (normal culture), salidroside low-dose group (10 μmol/L salidroside), salidroside medium-dose group (20 μmol/L salidroside), salidroside high-dose group (40 μmol/L salidroside), miR-NC group (40 μmol/L salidroside+miR-NC), miR-26a-5p inhibitor group (40 μmol/L salidroside+miR-26a-5p inhibitor), sh-RNA group (40 μmol/L salidroside+miR-26a-5p inhibitor+sh-RNA) and sh-JAG1 group (40 μmol/L salidroside+miR-26a-5p inhibitor+sh-JAG1). Cells in each group were treated with salidroside for 24 h after transfection or directly treated with the corresponding dosage of salidroside for 24 h. The relative mRNA expressions of miR-26a-5p and JAG1  in tissues and cells were quantified using qRT-PCR. Cell proliferating viability was measured by the MTT assay and cell cloning capacity was detected using the plate cloning method. Cell apoptosis was detected by FACS and cell migration and invasion were assessed by Transwell method. Luciferase reporter system was utilized to examine the targeting interaction between miR-26a-5p and JAG1. Western blotting was used to detect the expressions of tissue hyperplasia-related proteins. The results showed that, compared to that of the normal group, the expression of miR-26a-5p in keloid group was significantly decreased (P＜0.05), while the JAG1  expression significantly increased (P＜0.05). Compared to the 0 μmol/L salidroside group, 10, 20, 40, 80, and 160 μmol/L salidroside treatment inhibited the survival rate of keloid fibroblasts in a concentration-dependent manner (all with P＜0.05). To ensure both the survival of keloid fibroblasts and the effect of salidroside, subsequent experiments were conducted with salidroside concentrations of 10, 20, and 40 μmol/L (It was proved that miR-26a-5p combines to JAG1). In the three salidroside groups, compared to those of the control group, the expression of miR-26a-5p and the apoptosis rate increased dependently, while the expression of JAG1, the numbers of cell clones, cell migrations, and invasions, and the expression of α-SMA, collagen Ⅰ, collagen Ⅲ, JAG1, and Notch3 proteins decreased significantly (all with P＜0.05). Compared to those of the salidroside high-dose group and the miR-NC group, the expression of miR-26a-5p and the cell apoptosis rate in the miR-26a-5p inhibitor group reduced significantly, while the expression of JAG1, the numbers of cell clones, migration and invasion, and the expression of α-SMA, collagen Ⅰ, collagen Ⅲ, JAG1 and Notch3 proteins increased significantly (all with P＜0.05). Inhibition of JAG1  expression suppressed the effect of miR-26a-5p inhibitor on promoting cell proliferation, migration and invasion, and on inhibiting cell apoptosis. In conclusion, the expression of miR-26a-5p is down-regulated and JAG1  is up-regulated in keloid tissue, salidroside can inhibit the JAG1/Notch3 signaling pathway and the proliferation, migration and invasion of keloid fibroblasts, while promoting cell apoptosis, which in turn improves keloid by up-regulating the expression of miR-26a-5p.

Age-associated B cell (ABC) is a new B cell subset discovered in recent years, which accumulates in spleen with age. This type of cell has unique cellular phenotypes and transcriptional features. ABC highly expresses myeloid marker CD11c and transcription factor T-bet, and differentiates and proliferates upon the stimulation of Th1 cytokines and TLR7 and/or TLR9. It can differentiate into plasma cells to produce antibodies, secrete cytokines, and present antigens. ABC plays an important role in immune aging and autoimmune disease. This review aims to introduce the phenotypic characteristics, origin, anatomical distribution, differentiation regulation mechanism, and function of ABC, clarify its role in immune aging and autoimmune diseases, and provide a new target for clinical treatment.

Signet ring cell carcinoma (SRCC) is a rare but distinctive pathological subtype of colorectal cancer (CRC) with a mucin-rich phenotype as well as high metastatic rate and poor prognosis. In our large cohort of single-cell RNA sequencing (scRNA-seq) study of CRC, one case of SRCC was serendipitously enrolled. It is currently the first scRNA-seq data of SRCC derived from CRC in the world. Using this batch of scRNA-seq data including the SRCC, we aimed to compare the SRCC case with common adenocarcinoma (AC) in order to elucidate the cellular and molecular mechanisms behind SRCC. The results suggested that goblet-like malignant cells in SRCC contributed to its unique phenotypes. These cells specifically upregulated protein processing and cell adhesion related signaling pathways and overexpressed multiple mucin genes. Epithelial to mesenchymal transition (EMT) was associated with CRC metastasis. SRCC exhibited high level of EMT, in accordance with its high malignancy. However, the EMT related genes in SRCC were different from those of common AC. The potential prognostic role of genes related to EMT was revealed by combining the transcriptomic data and follow-up information of CRC in The Cancer Genome Atlas (TCGA) database. Compared to AC, SRCC had a smaller proportion of lymphocytes and a larger proportion of myeloid cells, and the correlation between epithelial and immune cells was reduced. Collagen and integrins interacted extensively between epithelial cells and stromal cells in CRC. This study is the first to characterize colorectal SRCC at the single cell level which is a powerful complement to the single-cell atlas of CRC, and provides new insights into the therapeutic targets of colorectal SRCC. 

Protein kinase CK2 is a highly conserved and ubiquitous protein kinase which phosphorylates a variety of protein substrates, and is involved in the regulation of several signaling pathways. Abnormal CK2 expression can lead to dysregulation of various signaling pathways, which is closely related to tumorigenesis and progression. This review summarizes the composition, structure and regulatory role of CK2 in important tumor-related signaling pathways and provides foundation to further explore CK2-targeted therapeutic strategies in cancer.

Inflammatory diseases are a series of acute or chronic diseases caused by inflammatory response to stimulation, which may seriously harm human health. Traditional Chinese medicine, which has multiple targets in immunomodulatory processes, plays a key role in the treatment of various inflammatory diseases. Corilagin is one of the major bioactive compounds in many medicinal plants. It has a variety of biological and pharmacological activities, including anti-oxidation, anti-inflammatory, liver protection, anti-virus, anti-hypertension, anti-infection, and anti-tumor. It has attracted extensive attention in recent years. However, there is a lack of systematic understanding of the role corilagin plays in inflammatory diseases. To better develop and utilize the medicinal plant resources in China, this review summarizes the role and related mechanism of corilagin in various inflammatory diseases. It will provide references for both follow-up basic research and clinical application of corilagin.

Aging is an inevitable stage in the metabolic process of human body which also affects the immune system, among which the changes of T cells are the most obvious. Mitochondrial dysfunction is one of the important reasons for cellular senescence. Recent studies have shown that viral infection can alter the metabolism of host cells by inducing mitochondrial damage which causes immunosenescence. This review aims to summarize the research progress on the role of virus infection-induced mitochondrial damage in T cell senescence including mitochondrial function, the effect of virus infection on mitochondrial damage, and the relationship between mitochondrial damage and T cell senescence.

This study aims to investigate the protein and mRNA expressions of IL-22 and aryl hydrocarbon receptor （AhR）in the peripheral blood of patients with systemic lupus erythematosus (SLE), and to analyze the correlation between IL-22 and AhR and SLE disease activity index (SLEDAI). The expression levels of IL-22 and AhR protein in the peripheral blood of 43 SLE patients (25 in active stage and 18 in inactive stage) and 41 healthy controls were measured by ELISA. The expression levels of IL-22 and AhR mRNA in PBMC of SLE patients, healthy controls, and 31 rheumatoid arthritis (RA) patients by qRT-PCR. Spearman analysis was used to calculate the correlations of IL-22 and AhR protein and mRNA levels with the SLEDAI in SLE patients. ROC curve was used to analyze the combined diagnostic effect of anti-dsDNA antibody, IL-22, and AhR protein levels in SLE. The results showed that the levels of IL-22, AhR protein and mRNA were higher in SLE patients than those in healthy controls (P<0.001), and they were all higher in the active phase than in the inactive phase (P<0.05). IL-22 expressions were significantly elevated in SLE patients compared to RA patients (P<0.05). Spearman analysis showed that IL-22, AhR protein and mRNA levels were all positively correlated with SLEDAI in SLE patients (P<0.01). The AUC of combined diagnosis of IL-22, AhR, and anti-dsDNA antibody for SLE was 0.986, with a sensitivity and specificity of 90.7% and 97.6%, respectively. In conclusion, the protein and mRNA levels of IL-22, AhR in SLE patients are significantly higher than those in healthy subjects and are positively correlated with SLEDAI. The diagnosis of serum IL-22 and AhR combined with anti-dsDNA antibody has higher accuracy and may improve the clinical diagnosis of SLE in the future.

Obesity increases the risk of infectious and neoplastic diseases. Studies have found that obesity may cause T cell metabolism disorders by affecting T cell lipid and carbohydrate metabolisms, promoting the release of inflammatory factors, and T cell aging, thereby increasing the mortality upon infection. Obesity is also an important risk factor associated with the prevalence of diseases. Obesity is associated with poor prognosis of neoplastic diseases, which is the combined effect of multiple factors affecting immune metabolism and inflammation. This review summarizes the research progress on T lymphocyte metabolism disorders caused by obesity and the role of T lymphocyte metabolism disorders in infectious and neoplastic diseases and treatment prospects.

Natural killer cell receptor group Ⅱ member A (NKG2A) is an inhibitory receptor of the NKG2 receptor family, which is mainly expressed on a variety of immune cells represented by NK cells. Studies have also revealed that NKG2A is involved in the development of a variety of tumors. NKG2A targeting drugs are currently in clinical phase trials for multiple epithelial tumors. The review describes the biological properties of NKG2A and its regulatory role on CD8⁺ T cells, NK cells, and other immune cells. The review further explores the mechanism of NKG2A as an immune checkpoint in anti-tumor immunity, and provides a theoretical basis for clinical anti-tumor immunotherapy.

To investigate the effect of leonurine (LEO) on Henoch-Schonlein purpura nephritis (HSPN), mice were divided into the blank control group, the model group, the low (25 mg/[kg·d]), medium (50 mg/[kg·d]) and high (100 mg/[kg·d]) doses of LEO treatment groups. The 24-hour urinary albumin (Alb) content was measured by the Bradford method and urine red blood cells were counted. The serum creatinine (Cr) and blood urea nitrogen (BUN) were measured by the automatic biochemical analyzer. Immunofluorescence staining was used to detect IgA deposition in renal tissues. The histopathological changes in renal tissues were observed by H-E staining. ELISA was performed to detect serum IL-4, IL-10, IFN-γ, and TNF-α. Serum circulating immune complex levels were measured by polyethylene glycol precipitation turbidimetry, and the peripheral blood Th1/Th2 ratio was measured by flow cytometry. The results showed that compared to those of the blank control group, the 24-hour urinary Alb level, urine red blood cell count, and serum levels of Cr, BUN, IL-4, IL-10, and circulating immune complex of the model group were significantly higher, whereas the serum IFN-γ, TNF-α levels, and peripheral blood Th1/Th2 ratio were significantly lower (P<0.05). Compared to those of the model group, the 24-hour urinary Alb level, urine red blood cell count, serum Cr, BUN, IL-4, IL-10, and circulating immune complex levels were significantly reduced, while the serum IFN-γ, TNF-α levels, and peripheral blood Th1/Th2 ratio were significantly increased in all the LEO treatment mice (P<0.05). In addition, the effect of LEO was dose-dependent (P<0.05). Taken together, this study suggests that LEO treatment reduces renal tissue damage and improves renal function and renal protection in HSPN mice. The underlying mechanism may be related to the promotion of Th1/Th2 balance which helps to restore normal immune function.

The poliovirus receptor (PVR) gene is closely related to tumorogenesis and development, while the regulatory roles and mechanisms of PVR in tumor immunity are not fully elucidated. This study analyzed the expression of PVR in different types of tumor tissues from a pan-cancer perspective and its correlation with patients prognosis and immunity. The analysis of the expression differences of PVR between cancerous and normal tissues was based on The Cancer Genome Atlas (TCGA) and TIMER database, and the correlation between PVR and the prognosis of cancer patients was assessed using survival analysis tools. Expression analyses of PVR in various with immune cells infiltration, immune checkpoint (ICP) genes expression and stromal/immune scoring were evaluated by the TIMER database and R software. To further understand the potential biological mechanisms of PVR  in various cancers, single-cell level sequencing and Gene Set Enrichment Analysis (GSEA)  were performed. The expression of PVR was verified by qRT-PCR in a variety of cancer cell lines. The results showed that, compared to that of normal tissues, PVR was significantly differentially expressed in tumor tissues like bladder urothelial carcinoma, cholangiocarcinoma, colon adenocarcinoma, esophageal carcinoma, and head & neck squamous cell carcinoma, etc. Aberrant expression of PVR was associated with poor prognosis for multiple cancers including adrenocortical cancer, bladder urothelial carcinoma, breast invasive carcinoma, and cervical carcinoma, etc. PVR expression was significantly correlated with immune cells infiltration, stromal/immune scoring and the regulation of ICP genes expression on pan-cancer level (all with P＜0.05). Single-cell sequencing outcomes showed that PVR was associated with tumor cells multiple cytobiological functions and phenotypes, including cell differentiation, gene silencing and DNA repairing. GSEA revealed that PVR was engaged in immune-related functions and signaling pathways in multiple tumor cells. The qRT-PCR results showed that PVR was highly expressed in stomach, colon and hepatocellular carcinoma cell lines compared to healthy cells. This comprehensive pan-cancer analysis suggests that PVR is an oncogene highly expressed in tumor tissues and leads to poor prognosis. Therefore, PVR may be a new immune-dependent prognosis-predicting marker that may provide new directions for targeted oncotherapy.

This study aimed to investigate the effects of sodium butyrate (NaB) on plaque formation and inflammatory responses in atherosclerotic (AS) rats through the nucleotide-binding oligodomain-like receptor 1 (NOD1)/receptor-interacting protein 2 (RIP2)/NF-κB signaling pathway. AS model on 41 rats was given by combination of balloon injury and high-fat diet (HFD), and a total of thirty-six rats were successfully modeled. Thirty-six AS rats were divided into model group, NaB group, and NaB+NOD1 agonist γ-D-glu-mesodiaminopimelic acid (iE-DAP) group, with 12 rats in each group. The sham operation group rats were only given exposure of left common carotid artery and successive suture. The model group, NaB group and NaB+iE-DAP group were cultured with HFD while the sham operation group was cultured routinely.  NaB group was gavaged with 10 g/(kg·d) NaB, NaB+iE-DAP group was gavaged with 10 g/(kg·d) NaB and peritoneally injected with 1 mL/(each·week) iE-DAP; Model group and sham operation group were gavaged and peritoneally injected with the same volume saline; All the above treatments lasted for twelve weeks. Aorta histomorphology was evaluated by H-E staining. The levels of serum TG, TC, LDL-C, HDL-C, ox-LDL, MCP-1, hs-CRP, TNF-α, and IL-1 were measured by ELISA. Immunohistochemistry was performed to measure ICAM-1 protein expression in the aorta and western blotting was used to measure the protein levels of NOD1, RIP2 and NF-κB in the aorta. The results showed that the aorta lesion was severe in the model group, alleviated in the NaB group and aggravated in the NaB+iE-DAP group. Compared to those of the sham operation group, the serum levels of TG, TC, LDL-C, ox-LDL, MCP-1, hs-CRP, TNF-α，and IL-1, the positive rate of aortic ICAM-1, the expression levels of NOD1, RIP2 and nuclear NF-κB in the model group were significantly increased (all with P＜0.05), while the levels of HDL-C and cytoplasmic NF-κB protein were significantly decreased (both P＜0.05). In the NaB group, all these indexes showed changes in the reverse direction. Compared to those of the NaB group, the above indicators in the NaB+iE-DAP group all increased significantly while HDL-C and cytoplasmic expression of NF-κB decreased (all with P＜0.05). This study suggests that NaB inhibit NOD1/RIP2/NF-κB signaling pathway to relieve plaque formation and inflammatory responses in AS rats.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of bone marrow-derived cells that are abundantly accumulated in patients and mouse models of diabetic nephropathy (DN). Studies have shown that MDSC-derived exosomes (EXs) have obvious immuno-suppressive functions, which may inhibit the development of inflammation in DN. This study aims to investigate the immuno-suppressive capacity of EX derived from MDSC (MDSC-EX) and its effect on DN mice. DN mice were established through high-fat diet and intra-peritoneal injection of streptozotocin (STZ). Two subsets of MDSC, polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (MO-MDSC), were isolated from DN mice spleens by magnetic-activated cell-sorting (MACS). PMN-MDSC and MO-MDSC-derived EXs were prepared from the culture supernatants of PMN-MDSCs and MO-MDSCs and FACS was used to examine their inhibitory effect on CD3⁺T cell proliferation. PMN-MDSC-EX or MO-MDSC-EX were caudal vein injected into DN mice and the effects on fasting blood glucose (FBG）, body weight (BW), total protein in urine within 24 hours (TPU), urea nitrogen in serum (UNS), creatinine in serum (CS) and glomerular filtration rate (GFR) were observed. H-E staining of kidney was observed under microscope and the protein expressions of fibronectin, collagen type Ⅳ (collagen Ⅳ), and alpha smooth muscle actin (α-SMA) in kidney tissues were measured by western blotting. The results showed the successful establishment of  DN mouse model and the isolation of PMN-MDSC-EX and MO-MDSC-EX. Compared to MO-MDSC-EX, PMN-MDSC-EX had a greater capacity to inhibit the proliferation of CD3⁺T lymphocytes (P＜0.05). Compared to MO-MDSC-EX, PMN-MDSC-EX decreased the FBG, TPU, UNS, and CS in DN mice to a larger extent, and increased the BW and GFR significantly (all with P＜0.05). Intervention with both PMN-MDSC-EX and MO-MDSC-EX significantly alleviated kidney tissue damage in DN mice. Compared to MO-MDSC-EX, PMN-MDSC-EX presented a better inhibitory effect on glomerulosclerosis in model mice. In conclusion, PMN-MDSC-EX has a stronger protective effect on DN mice than MO-MDSC-EX, which highlights a novel path to DN treatment.

The aim of this study is to explore the protective effect and mechanism of rosmarinic acid (RA) on rats with sepsis and acute kidney injury. The kidney injury models of sepsis were constructed by cecal ligation and puncture (CLP) and the rats were randomly divided into sham operation group, model group, RA groups (12.5, 25, 50 mg/kg), and dexamethasone (Dex, 1 mg/kg) group. H-E staining of kidney tissues, renal function indexes, oxidative stress indexes, apoptosis of kidney tissues, and expressions of NF-κB and p38 MAPK signaling pathway proteins were compared among the groups. The results showed that compared to the model group, the RA groups (25, 50 mg/kg) and Dex group had significantly decreased levels of serum creatinine (Scr), blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), TNF-α, IL-1β, IL-6, malondialdehyde (MDA), number of apoptosis cells in kidney tissues, cleaved Caspase-3/Caspase-3, cytochrome c (Cyt c), cleaved poly(ADP-ribose) polymerase (cleaved PARP), phosphorylated p65 (p-p65)/p65 and phosphorylated p38 (p-p38)/p38 (P<0.05). In contrast, the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased in RA groups (25, 50 mg/kg) and Dex group (P<0.05). In addition, the improvement of the above indexes was more significant in RA group (50 mg/kg) and Dex group (P<0.05). The study suggests that RA inhibits NF-κB and p38 MAPK signaling pathways, alleviates inflammation response and oxidative stress, and reduces apoptosis of kidney tissues to improve sepsis and acute kidney injury.

To explore the effect of matrix metalloproteinase 7 (MMP-7) over-expression on macrophage polarization, galectin 3 (Gal-3) and inflammatory factors secretions, THP-1 cells were induced to macrophages and transfected with MMP-7 over-expressing plasmid or empty vector. The cells were divided into control group, MMP-7 over-expressing group, MMP-7 NC group, M1-polarized group, and M2-polarized group. mRNA expression levels of Gal-3 and MMP-7 were quantified by qPCR. The percentages of F4/80⁺, CD86⁺, and CD206⁺ macrophages were detected by flow cytometry. The expressions of inflammatory cytokines IL-1α, IL-6, and TGF-β were detected by ELISA. After Gal-3 inhibitor treatment on M1-induced and M2-induced macrophages, the mRNA expression of Gal-3 in above macrophages was detected by qPCR, and the levels of IL-1α, IL-6, and TGF-β in the supernatant of cell cultures were detected by ELISA. The results showed that compared to the control group, the MMP-7 over-expressing group and the M2-polarized group showed significant increase in the expressions of Gal-3 and MMP-7 mRNA, in the percentage of (F4/80⁺)/CD206⁺ macrophages (all with P＜0.01), and in the concentrations of TGF-β（both P＜0.01), while IL-1α and IL-6 levels showed significant decrease (both P＜0.01). In the M1-polarized group, the percentage of (F4/80⁺)/CD86⁺ macrophages increased significantly (P＜0.01). The concentration of TGF-β decreased, while the concentrations of IL-1α and IL-6 increased significantly (all with P＜0.01). Compared to that of the M1-polarized group, the relative expression of Gal-3 mRNA in the M1+Gal-3 inhibitor group was significantly decreased (P＜0.01), the concentration of TGF-β significantly increased (P＜0.01), while the IL-1α and IL-6 levels significantly decreased (both P＜0.01). Compared to those of the M2-polarized group, the relative expression of Gal-3 mRNA in M2+Gal-3 inhibitor group was significantly decreased (P＜0.05), along with decreased IL-1α and IL-6 and increased TGF-β concentrations (all with P＜0.05). This study demonstrates that MMP-7 can activate Gal-3 expression to promote M2-type macrophage polarization and present anti-inflammatory activity.

The incidence of Alzheimer's disease (AD) among the elderly is extremely high. At present, the most well-known pathological changes are hyperphosphorylated tau protein entanglement and amyloid β-protein (Aβ) deposition. Remarkably, the immune inflammatory response also plays an important role in the pathogenesis of AD, and microglia plays the main role in the process of neuroinflammatory response. In brain, triggering receptor expressed on myeloid cells 2 (TREM2) is mainly expressed in microglia, which not only regulates the metabolism, survival, phagocytosis, and proliferation of microglia, but also regulates the  polarization of microglia from M1 type to M2. Over the years, growing evidence has demonstrated that TREM2-mediated  immure response leads to the improvement of  AD pathology. This article reviews the effects of TREM2 and microglia on the central nervous system and AD biogenesis.

Aiming to explore the underlying mechanism of Zhilong Tongluo capsule on protecting rats with adriamycin(ADR)-induced nephropathy from renal fibrosis, renal fibrosis rat model was established by right side nephrectomy and multiple caudal vein injections of 3 mg/kg ADR. After successful model establishment, rats were divided into model group, Zhilong Tongluo capsule group and Zhilong Tongluo capsule+activator group, and rats without treatment were used as control. Rats in Zhilong Tongluo capsule group were gavaged with Zhilong Tongluo capsule suspension, rats in Zhilong Tongluo capsule+activator group were additionally intraperitoneally injected with LPS (5 mg/kg), and rats in blank control group and model group were treated with same volume of saline. All treatments lasted for 8 weeks. The general conditions of rats and body weight (BW) changes were recorded. The 24 h urine protein (24 h UPO), creatinine (Cr), and blood urea nitrogen (BUN) were detected by urine protein quantification kit and ELISA kit. The rats were sacrificed and then renal tissues were collected for pathological study. The fibrosis of renal tissues was observed after Masson staining. The mRNA and protein levels of TLR4, NF-κB, and TGF-β1 were measured by qRT-PCR and immunohistochemistry. Compared to that of the blank control group, BW was decreased, while the collagen proportionate area (CPA), 24 h UPO, Cr, and BUN were increased in the model group. The mRNA and protein levels of TLR4, NF-κB, and TGF-β1  were also significantly increased (all with P＜0.05). Compared to those of the model group, the BW of rats was increased, and CPA, 24 h UPO, Cr, and BUN were decreased in the Zhilong Tongluo capsule group. The mRNA and protein levels of TLR4, NF-κB, and TGF-β1  were significantly decreased (all with P＜0.05). Compared to those of the Zhilong Tongluo capsule group, the BW was decreased, CPA, 24 h UPO, Cr, and BUN were increased in the Zhilong Tongluo capsule+activator group while the mRNA and protein levels of TLR4, NF-κB, and TGF-β1  were all significantly increased (all with P＜0.05). In conclusion, Zhilong Tongluo capsule may mitigate fibrosis of renal tissues and alleviate renal damage by inhibiting the expression of the TLR4/NF-κB/TGF-β1 signaling pathway.

The aim of this study is to investigate the effect and mechanism of indolepropionic acid (IPA) on LPS-induced proliferation, apoptosis, and inflammatory response of peritoneal mesothelial cells. Firstly, mouse peritoneal mesothelial cells were treated with 0.1, 1.0, and 10 μmol/L IPA, respectively. After 24 h, CCK-8 method was used to detect the cytotoxicity of IPA. Next, cells were pretreated with 0.1, 1.0, and 10 μmol/L IPA for 2 h, followed by treatment of 10 mg/L LPS for 24 h. CCK-8 method was used to detect the proliferation ability of cells, and the optimal working concentration of IPA was determined. The cells were divided into 5 groups: control group, LPS group, LPS+IPA group, LPS+QNZ (a NF-κB pathway inhibitor) group, and LPS+QNZ+IPA group. CCK-8 method was used to detect cell proliferation, and flow cytometry was used to detect cell apoptosis. ELISA was used to detect the level of TNF-α in the cell supernatant, and Western blotting was used to detect the  expressions of NF-κB p65 and p-p65 in the cells. The results showed that 0.1 and 1.0 μmol/L IPA had no cytotoxicity on mouse peritoneal mesothelial cells, and the optimal working concentration of IPA was 1.0 μmol/L. Compared to those of control group, the proliferation ability of LPS group was significantly decreased (P<0.01), while the apoptosis rate, the level of TNF-α in the cell supernatant, and the phosphorylation level of NF-κB p65  in the cells were all significantly increased (P<0.01). Compared to that of the LPS group, the proliferation ability of LPS+IPA group, LPS+QNZ group, and LPS+QNZ+IPA group was significantly increased (P<0.01), while the apoptosis rate, the level of TNF-α in the cell supernatant, and the phosphorylation level of NF-κB p65  in the cells were significantly decreased (P<0.05). Therefore,LPS+QNZ+IPA combination showed the most significant effect. In summary, these results indicate that IPA promotes the proliferation of mouse peritoneal mesothelial cells induced by LPS, and inhibits cell apoptosis and inflammation. The underlying mechanism may be related to the inhibition of NF-κB pathway activation.

The aim of this study was to investigate the effect of suppressor of cytokine signaling 3 (SOCS3) on the  high glucose(HG)-induced inflammatory factors expression in rat glomerular mesangial cell (RMC) and the related mechanism. For this purpose, RMCs were divided into six groups: normal control (NC) group, osmotic control (OSM) group, HG group, HG+TAK-242 (TLR4 inhibitor) group, HG+sh-SOCS3 group, and HG+sh-SOCS3+TAK-242 group. Cell viability was detected by CCK-8 assay and cell apoptosis was detected by FACS. The levels of inflammatory factors TNF-α, IL-1β, IL-6, and COX2 in cell culture supernatant were detected by ELISA. The mRNA expressions of TLR4, NF-κB p65, and IκB-α in RMC were detected by qPCR. The protein expressions of TLR4, NF-κB p65, p-p65, IκB-α, and p-IκB-α were detected by western blotting. The results showed that compared to those of  NC group, the cell survival rate of the HG group was significantly decreased (P＜0.01), while the cell apoptosis rate, the levels of TNF-α, IL-1β, IL-6 and COX2 in cell culture supernatant, the mRNA expression of TLR4, p65 and IκB-α and the protein expression of TLR4、p-p65 and p-IκB-α were significantly increased (all with P＜0.01). Compared to those of  HG group, the cell survival rates of the HG+TAK-242 group and the HG+sh-SOCS3 group were significantly increased (both P＜0.05) while the apoptosis rate, the levels of TNF-α, IL-1β, IL-6 and COX2 in the cell culture supernatant, the mRNA expression of TLR4, p65, and IκB-α, and the protein expression of TLR4, p-p65, and p-IκB-α were significantly decreased (all with P＜0.05). The above changes were more significant in the HG+sh-SOCS3+TAK-242 group than the HG+TAK-242 group (all with P＜0.05). Taken together, SOCS3 up-regulates the expression of inflammatory factors in RMCs cultured with HG by activating the TLR4/NF-κB signaling pathway, thus aggravates the inflammatory responses.

The aim of this study is to investigate whether curcumin  reduces liver injury in rats with non-alcoholic fatty liver disease (NAFLD) by regulating TNF-α/NF-κB signaling pathway through miR-155. The effect of curcumin on the degree of injury of NAFLD rats was observed by histopathology. Changes in blood lipids and liver function were detected by serological tests, and levels of inflammatory factor (TNF-α) were detected by ELISA in rats in different groups.The expressions of TNF-α, inhibitor of NF-κB (IκBα), NF-κB p65 and p-NF-κB p65 were detected by qRT-PCR and Western blotting, respectively. The results showed that compared to those of the model group, the degree of steatosis and inflammation in livers of rats treated by different doses of curcumin or in the NF-κB inhibition group were all significantly reduced, and the tissue lesions degree was significantly alleviated. In addition, serum levels of alanine amino-transferase (ALT), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were all significantly decreased (P<0.05), while total protein (TP), albumin (Alb), and high-density lipoprotein cholesterol (HDL-C) were all significantly increased (P<0.05). On the other hand, the release of TNF-α in both serum and liver tissues was significantly decreased (P<0.01), along with decreased relative expression of miR-155 and NF-κB p65 in liver tissues (P<0.01), and the relative expression of IκBα was significantly increased (P<0.01).In addition, the effect was more significant with combined intervention of curcumin and NF-κB inhibitor. This study suggests that curcumin may regulate TNF-α/NF-κB signaling pathway through miR-155 to reduce liver    injury in NAFLD rats.

To investigate the role of host G-protein-coupled receptor 84 (GPR84) upon mycobacterial infection, GPR84 mutant zebrafish model was established to assess the effect of GPR84 on Mycobacterium marinum (M.m.) proliferation and host survival. Mechanistically, the effect of GPR84 on macrophage and neutrophil development was first excluded by neutral red staining and Sudan black staining, respectively. The effect of GPR84 deficiency on neutrophil recruitment was evaluated by zebrafish tail amputation assay. Moreover, the formation of lipid droplets in infected zebrafish was detected by oil red O staining, and the transcription levels of genes related to lipid metabolism and inflammatory factors in infected models were detected by qRT-PCR. The results of the above experiments showed that transient knockout of GPR84 in zebrafish inhibited the proliferation of M.m. in vivo and prolonged host survival, whereas GPR84 deficiency did not affect the development of macrophages and neutrophils, or the recruitment of neutrophils. Further studies revealed that GPR84 mutant zebrafish presented reduced lipid droplets formation after mycobacterial infection and was accompanied by down-regulation of cholesterol efflux pump gene ATP-binding cassette transporter G1 (ABCG1), meanwhile inflammatory factors expression was up-regulated. This study suggests that mycobacterial infection may induce lipid droplets formation through host GPR84 to suppress inflammatory factors expression and ultimately facilitates the process of bacterial infection.

Celiac disease (CeD) is a type of intestine autoimmune disease caused by the intake of grains containing gluten protein in susceptible gene carriers. Genetic factors play an important role in the pathogenesis. Almost all CeD patients carry HLA-DQ2/DQ8, which accounts for about 40% of the disease genetic causes, while the remaining 60% of cases are attributed to a large number of non-HLA genes. The genome-wide association study (GWAS) has found that over 50 non-HLA genes are associated with CeD pathogenesis, but currently discovered non-HLA genes can only explain about 15% of genetic susceptibility, and there are a large number of non-HLA genes that yet to be discovered. This review focuses on the research progress of CeD susceptible genes, providing ideas and methods for a deeper understanding of the pathogenesis of CeD and for subsequent diagnosis and therapy.

Sex hormones are steroid hormones secreted by gonads and adrenal glands or converted from other substances. Sjogren's syndrome (SS) is a chronic progressive systemic autoimmune disease mediated by lymphocytes, mainly affecting exocrine glands. Due to the complex etiology, its pathogenesis has not been fully elucidated. The fact that the incidence of SS is higher in women than in men suggests a relationship between sex hormones and the development of SS. This review discusses the mechanism and influence of estrogen, androgen, and prolactin on SS to provide reference to understand the pathogenesis of SS and explore the therapeutic strategies.

The tumor microenvironment (TME) is a complex cellular environment around tumor consisting of tumor cells, immune cells, and stromal cells, which plays a crucial role in tumorigenesis. Among tumor-infiltrated immune cells, a major composition and functional significant population is the myeloid cells (including tumor-associated macrophage [TAM], mast cell [MC], DC, tumor-associated neutrophil [TAN], and myeloid-derived suppressor cell [MDSC]). They have a complex dual regulatory role in both cancer promotion and suppression and affect tumor growth, invasion, metastasis, and death. This review focuses on the research progress of how multiple myeloid cells in the TME regulate the occurrence and development of hepatocellular carcinoma (HCC).

PD-L2 binds to PD-1 to inhibit T cell proliferation and cytokine production, while its interaction with repulsive guidance molecule b (RGMb) has the opposite effect. Researches revealed that PD-L2 is abnormally expressed in the peripheral blood and corresponding tissues of patients with tumors or autoimmune diseases, and participates in disease progression by glycosylation modifications and interactions with immune cells. In order to fully understand the regulation and expression of PD-L2 and its regulation on tumors and autoimmune diseases after binding to receptors, this review first elucidates the biological characteristics of PD-L2 and discusses its involvement in disease progression, then summarizes the research progress of PD-L2 on cancer and autoimmune diseases, and finally summarizes the prospect of its research value, aiming to provide new ideas for the research and treatment of various diseases including tumor.

This study aimed to screen and identify abnormally expressed cytokines in the serum of patients with SLE and to explore their clinical significance. Liquid-phase microarray technique was used to detect the expression differences of 45 cytokines spectrum in 3 SLE patients and 3 healthy individuals. Subsequently, ELISA was used to verify the most differentially expressed cytokines in 54 SLE patients and 28 healthy individuals, and their correlations with SLE disease activity index 2000 (SLEDAI-2K) score, typic laboratory indicators and renal involvement were studied. The results showed that a total of 15 cytokines were highly expressed in the sera of SLE patients, and 4 most significant differentially expressed cytokines were picked out  based on the fold differences. Further testing found that the serum levels of IL-6, IL-10, IL-1 receptor antagonist (IL-1Ra) and    IFN-γ-inducible protein 10 (IP-10) were significantly higher in SLE patients than in healthy controls(all with P＜0.05). Among them the serum levels of IL-10 and IL-1Ra were positively correlated with the SLEDAI-2K score in SLE patients. In addition, serum IL-10 levels were positively correlated with serum IgG and ESR, while the serum IL-1Ra levels were negatively correlated with complement C3 and complement C4(all with P＜0.05). Furthermore, the serum IL-1Ra levels were positively correlated with total  protein in urine within 24 hours (TPU)  in SLE patients(P＜0.001). Collectively, above data indicates that multiple cytokines were abnormally expressed in SLE patients. The serum levels of IL-10 and IL-1Ra are related to the disease activity of SLE, and the serum IL-1Ra  could be associated with SLE renal involvement. Detection of these indicators may provide proofs for clinical diagnosis, treatment, and monitoring of SLE.

To investigate the effects and mechanism of D-limonene, the active ingredient of Xiefeiqingganyin, on inflammatory and immune responses in mice with chronic obstructive pulmonary disease (COPD), 36 6-week-old male C57BL/6J mice were randomly divided into three groups: control group, model group, and D-limonene group, with 12 mice in each group. The COPD model were established by administration of LPS and smoking. Mice in D-limonene group were intraperitoneally injected with 100 mg/kg D-limonene daily from the 2nd day of modeling until the 28th day. The hair, movement, and mental state of mice in each group were observed, and the body mass was recorded. Pathological changes of mouse lung tissues were observed by H-E staining. Western blotting was used to detect the expression of NF-κB and p-NF-κB protein in lung tissues, and ELISA was used to detect the levels of IL-6, TNF-α, IL-1β, and IL-10 in serum and bronchoalveolar lavage fluid (BALF). FACS was used to detect the ratio of Th17/Treg in peripheral blood. The results showed that compared to control group, mice in model group showed more severe symptoms including weight loss, listless and decadent, dull coat and hair loss, reduced activity, abnormal alveolar structure, hyperplasia of bronchial epithelium, and increased infiltration of inflammatory cells around the lung tissues. In addition, the expression of p-NF-κB protein in lung tissue, the levels of IL-6, TNF-α, and IL-1β in serum and BALF, and the ratio of Th17/Treg in peripheral blood were all significantly increased (P<0.01), while IL-10 in serum and BALF was significantly decreased (P<0.01). These changes were significantly reversed after D-limonene administration (P<0.01). Altogether, this study suggests that D-limonene has a good therapeutic effect on COPD mice by restoring the Th17/Treg balance and reducing the expressions of inflammatory factors by inhibiting NF-κB pathway. 

To investigate the effect of circular RNA 0000885 (circ_0000885) on theproliferation, apoptosis and migration of glioma cells, and further to explore its potential mechanism，circ_0000885 and miR-186 expression in normal brain tissues and glioma tissues was analyzed using qRT-PCR. Dual luciferase reporter experiment verified the targeting relationship between circ_0000885 and miR-186. Small interfering RNA negative control (si-NC), circ_0000885 small interfering RNA (si-circ_0000885), miRNA mimic negative control (miR-NC), miR-186 mimic, miRNA inhibitor negative control (anti-miR-NC), miR-186 inhibitor (anti-miR-186), and si-circ_0000885 +anti-miR-186 were transfected into glioma cell line LN229. The effects of circ_0000885 and miR-186 expression on cell viability, colony formation, apoptosis and migration of LN229 cells was evaluated by cell counting kit (CCK-8), plate cloning experiment, flow cytometry, and Transwell experiment, respectively. The transplanted tumor volume was detected by the nude mouse xenograft experiment. The results showed that compared to that of the normal brain tissue, circ_0000885 expression in glioma tissue was significantly increased (P<0.05), while miR-186 expression was significantly decreased (P<0.05). Interfering with the expression of circ_0000885 or overexpressing miR-186 significantly decreased the viability, colony formation number, and migration number of LN229 cells (P<0.05), increased cell apoptosis rate and miR-186 expression level (P<0.05), while inhibiting the expression of miR-186 had the opposite effect. Inhibition of miR-186 expression significantly attenuated the effects of JP2interfering circ_0000885 expression on LN229 cell viability, colony formation, migration, apoptosis and xenograft growth. This study suggests that interfering with circ_0000885 inhibits the tumor proliferation and migration, and induces cell apoptosis of glioma cells by targeting and up-regulating miR-186.

To investigate the influences of naringin (NRG) on the proliferation and apoptosis of human rheumatoid arthritis fibroblast like synoviocytes (RA-FLS) mediated by the JAK/STAT3 pathway, RA-FLS were isolated from knee synovial tissue of RA patients and confirmed by the expressions of Vimentin and CD90 detected by immunofluorescence. RA-FLS were then divided into NC group (normally cultured RA-FLS), NRG-L group (20 μg/mL), NRG-M group (40 μg/mL), NRG-H group (80 μg/mL), and NRG-H+Coumermycin A1 (JAK activator) group (80 μg/mL NRG+10 μmol/L Coumermycin A1). The proliferation of RA-FLS was detected by the CCK-8 method and the morphology of apoptosis by Hoechst 33258 staining. The apoptotic rate of RA-FLS was detected by flow cytometry. The levels of IL-6, IL-1β and TNF-α in the culture supernatant of RA-FLS were detected by ELISA. The mRNA levels of proliferating cell nuclear antigen (PCNA) and Caspase-3 in RA-FLS were detected by qRT-PCR. And western blotting was used to detect the protein expressions of PCNA, Caspase-3, p-JAK2 and p-STAT3 in RA-FLS. The quality of RA-FLS isolation was confirmed by the spindle-shaped cells and strongly positive staining for vimentin and CD90. Compared to those of the NC group, the D（450 nm） value (24, 48 h) and the expressions of IL-6, IL-1β, TNF-α, PCNA at both mRNA and protein levels, as well as p-JAK2, p-STAT3 protein expressions were decreased of RA-FLS in the NRG-L group, NRG-M group and NRG-H group. On the other hand, the number of bright-staining cells, the apoptosis rate, and expression levels of Caspase-3 mRNA and protein were increased, in a dose-dependent manner (P<0.05). Compared to those of the NRG-H group, the D（450 nm） value (24 h, 48 h) and the levels of IL-6, IL-1β, TNF-α, PCNA at both mRNA and protein levels, as well as p-JAK2, p-STAT3 protein expression were increased in RA-FLS of NRG-H+Coumermycin A1 group, whereas the number of bright-staining cells, the apoptosis rate, Caspase-3 mRNA and protein expressions were decreased (P<0.05). Taken together, this study shows that NRG may inhibit the proliferation of RA-FLS and promote apoptosis by inhibiting JAK/STAT3 pathway.

At present, multiple myeloma (MM) remains an incurable disease. In recent years, immunotherapeutic drugs, represented by CD38 monoclonal antibody, have been widely used in the clinical practice and significantly prolonged the survival of MM patients. Meanwhile, a variety of highly effective novel immunotherapeutic agents such as chimeric antigen receptor (CAR)-T cell, antibody-drug conjugate (ADC), and bispecific antibody (BsAb) are continuously emerging, reshaping the treatment landscape of MM. This review summarizes the current development and challenges in the field of immunotherapy for MM, while also offering reflections and suggestions on the future direction of immunotherapy, for providing the reference in the field of MM diagnosis and treatment research.

Genetically engineered modification of antibodies generates various types of new small molecule antibodies, among which single-chain antibody (ScFv) has indisputable advantages including high specificity, high affinity, tissue permeability, excellent stability and low immunogenicity, easy preparation, and large-scale production, etc. ScFv has been widely applied in the fields of drug development and disease treatment. This review summarizes the new research progress and medical application of ScFv.

A magnetic particle chemiluminescence immunoassay (MPCLIA) for the detection of Candida mannan (Mn) was established. Monoclonal antibody was prepared by immunizing BALB/c mice with Candida Mn as antigen. The MPCLIA for Candida Mn detection was established by using automatic chemiluminescence analyzer and double-antibody sandwich method. The complex of streptavidin-magnetic particle-biotin labeled-Candida Mn-acridine sulfonamide labeled antibody was formed in the reaction system. The results showed that the limit of blank (LoB) was 2.0 pg/mL and the limit of detection (LoD) was 5.0 pg/mL. The linear range was 10.0~1 000.0 pg/mL. The variation coefficients of repeatability and of precision  were both less than 10%. The recovery rate was 85%～115%. When the concentrations of hemoglobin, bilirubin or triacylglycerol (TAG) reached 7 mg/mL, 300 mg/L and 7.5 mmol/L, respectively, there was no significant interference on the laboratory results. The results generated with this method were in line with clinical diagnosis outcomes (κ=0.79). Altogether, the Candida Mn MPCLIA established in this study has met the detection standards for in vitro diagnostic reagents, and  is expected to become a rapid immunological detection method of Candidiasis after  sufficient sample data promise.

This study aims to explore the regulatory effect of endogenous miR-221 on STAT3 and the molecular mechanism of immune escape in lung cancer cells. Quantitative PCR was used to detect the expressions of miR-221 and STAT3 mRNA in lung cancer tissues and adjacent normal tissues, and the correlation between miR-221 and STAT3 mRNA expression in cancer tissues was analyzed. Luciferase reporter system was used to determine the regulatory effect of miR-221 on STAT3. A549 lung cancer cells were cultured in vitro and divided into control group (mimic control group), miR-221 high expression group (miR-221 mimic transfection), and miR-221 low expression group (anti-miR-221 transfection). The expressions of STAT3 and p-STAT3 protein in each group were compared. The transfected cells were co-cultured with NK-92 cells at a ratio of 1∶5 and the expressions of IL-2, IFN-γ, and TNF-ɑ in culture supernatant were compared. The immune killing rate of NK-92 cells was also measured. The results showed that the expression levels of miR-221 and STAT3 mRNA in lung cancer tissue were significantly higher than those of the adjacent tissue, and there was a positive correlation between miR-221 and STAT3 mRNA in lung cancer tissue (P<0.05). Luciferase assay showed that miR-221 targeted and upregulated the expression of STAT3. The protein expressions of STAT3 and p-STAT3 in the miR-221 low expression group were lower than those of the control group and the high expression group. The protein levels of STAT3 and p-STAT in the high expression group were even higher than those of the control group (P<0.05). The immune killing rate of NK-92 cells and the secretion of IL-2, TNF-α and IFN-γ in the miR-221 low expression group were higher than those of the control group and the high expression group while these indicators in the miR-221 high expression group was lower than those of the control group (P<0.05). In conclusion, miR-221 is highly expressed in non-small cell lung cancer tissue, and upregulation of its expression can inhibit the killing activity of NK cells. The underlying mechanism may be related to the STAT3 mediated immune escape of lung cancer cells.

This report investigated the mechanism by which human bone marrow mesenchymal stem cells (hBMSC) inhibit neuronal apoptosis in vitro. H2O2 was used as an apoptotic inducer to human neuroblastoma cells (SH-SY5Y cells) or primary cultured mouse nerve cells. The antioxidant effect of hBMSC was evaluated by co-culturing hBMSC with SH-SY5Y cells or primary cultured mouse nerve cells. Specific tyrosine receptor kinase B (TrkB) inhibitors were used to block the brain-derived neurotrophic factor (BDNF)/TrKB pathway, and the changes in the antioxidant effect of hBMSC were observed. The results showed that H2O2 induced apoptosis in SH-SY5Y cells in a concentration and time-dependent manner. Of note, SH-SY5Y cells or primary cultured mouse nerve cells co-cultured with hBMSC showed reduced apoptosis. TrkB inhibitors blocked the BDNF/TrKB pathway and partially impaired the inhibitory effect of hBMSC on apoptosis. Our results show that hBMSC exert their inhibitory effects of neuronal apoptosis through BDNF/TrKB pathway in vitro.

The clinical data of 1 431 patients with lupus anticoagulant (LA) from Air Force Military Medical University Affiliated Xijing Hospital were collected to analyze the distribution  characteristics of LA in 4 major clinical departments and in disease types. Lab reports of the 1 431 cases with LA were retrospectively analyzed and patients were divided into 4 groups according to the affiliated clinical departments: A, B, C, and D. The percentage of detected size, LA positive rate, LA ratio median (M) and percentile (P) (P25, P75), 95% confidence interval (CI), and the percentage of disease types with positive results in groups A, B, C, and D were compared.The results showed that, among the 1 431 patients with LA report in the hospital, department of immunology （group A） accounted for the highest proportion (53%), with LA positive rate of 41%, M and 95% CI of 1.17 and 1.01～1.95, respectively, and the disease type was mainly SLE (33%). The obstetrics and gynecology reproductive center（group B） ranked second (35%) in patient number, and the positive rate was 29%, with M and (P25, P75)［1.15(1.10, 1.21)］ and 95% CI (1.01～1.42) being the lowest. Among the 4 groups, group C (department of emergency) had the highest positive rate (43%), and the M and (P25, P75)were the greatest ［1.19(1.10,1.36)］, with SLE encephalopathy (SLEE) being the dominant disease type for this group (37%). The 95% CI for group D was 1.01 to 2.98, owning the largest variation. In conclusion, among the 1 431 patients with  LA outcomes in Xijing hospital, SLE was the main disease type, among which SLEE from the department of neurology and lupus nephritis (LN) found in the department of nephrology were the most common and serious complications of SLE. In brief, prior to the detection of LA, it is necessary to fully evaluate whether patients meet the indications for detection, and further relevant examinations should be carried out in positive patients to avoid falling and misdiagnosis.

This study aims to investigate the changes in mRNA expressions of stimulator of interferon gene (STING) and cyclic GMP AMP synthase (cGAS), the composition of myeloid dendritic cells (mDC) and their surface maturation markers CD80 and CD86, the related cytokines, and the correlation among above indicators to analyze the immune response upon adenovirus pneumonia infection. 34 children with acute stage adenovirus pneumonia and 34 healthy children were included in the study. The relative mRNA expression levels of STING and cGAS in the peripheral mononuclear cells were detected by qRT-PCR. The levels of IFN-α, IFN-β, TNF-α, and IL-6 were detected by ELISA. FACS was used to detect the mDC composition and surface markers CD80 and CD86. The correlation of the above indicators was analyzed. The results showed that compared to those of the control group, mRNA expression levels of STING and cGAS, IFN-α, IFN-β, TNF-α, IL-6, mDC cell number, CD80, and CD86 were all increased in adenovirus pneumonia patients (P<0.05). The level of mDC was positively correlated with the expressions of STING mRNA, cGAS mRNA, IFN-α, TNF-α, and IL-6. The CD80 level was positively correlated with STING mRNA, cGAS mRNA, IFN-α, IFN-β, TNF-α, and IL-6, whereas CD86 was positively correlated with IFN-α, IFN-β, and TNF-α (P＜0.05). This study suggests that STING/cGAS genes are highly expressed in children with adenovirus pneumonia who exhibit increased mDC number, maturation markers, and cytokine secretion. The cGAS-STING pathway may be further activated to mediate innate immunity and exert antiviral effect.

The aim of this paper was to investigate the expression of myocyte enhancer factor 2A (MEF2A) gene in myeloproliferative neoplasm (MPN) and its relation with tumor cell proliferation and angiogenesis. From January 2020 to December 2021, PBMC specimens were collected from 30 healthy volunteers and 60 MPN patients in the Affiliated Hospital of Guilin Medical University. Additionally, MPN tumor cell lines HEL92.1.7 (abbreviated HEL), UKE-1, and SET-2 were cultured and used for cellular study. qRT-PCR and western blotting were used to detect the expression levels of MEF2A mRNA and protein. HEL and UKE-1 cells were transfected with MEF2A knock-down or over-expressing plasmid, respectively. Cell viability and monoclonal formation capacity were evaluated by CCK-8 assay and crystal violet staining. Cell apoptosis rate was measured by FACS with Annexin Ⅴ-FITC/PI double staining. The in vitro angiogenic ability was determined by catheter formation assay. The expressions of proteins related to apoptosis, angiogenesis and p38 MAPK signaling pathway were quantified by western blotting. The results showed that the mRNA and protein expressions of MEF2A in PBMCs of MPN patients were significantly higher than those of healthy volunteers (both P＜0.05). The expression levels of MEF2A mRNA and protein in MPN cell lines were also significantly higher than those of PBMCs from healthy  controls (all with P＜0.05). In HEL and UKE-1 cell lines, MEF2A over-expression caused increased cell proliferation, clone formation, angiogenesis, and the protein expressions of ANGPT2, FGF1, PDGFA, VEGF, Bcl-2, p-P38, and p-ERK (all with P＜0.05). In contrast, it decreased the cell apoptosis rate and the protein expressions of BAX and cleaved caspase 3 (cl-caspase-3)(all with P＜0.05). On the other hand, MEF2A knock-down resulted in the complete opposite effects (all with P＜0.05). In conclusion, MEF2A is broadly distributed in MPN cells at a relatively high level, and knock-down of MEF2A can inhibit the proliferation and angiogenesis while promoting the apoptosis of MPN tumor cells. MEF2A may function by regulating the MAPK signaling pathway.