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.

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.

Mast cells are innate immune cells, and matured mast cells are distributed throughout the body, mainly near blood vessels and nerves. Upon stimulation by IgE and other stimuli, degranulation process of mast cells occurs through acascade of signal transduction, releasing inflammatory factors and various cytokines. Mast cells therefore have complicated proinflammatory and immunoregulatory effects. This review focuses on the influence of mast cells on allergic diseases including the promotion of diseases through degranulation, immunoregulation and neuro-immune regulation, highlights the importance of mast cells in autoimmune diseases, discusses their immunoregulatory function in various organs and tissues and their dual effect to autoimmune diseases.

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.

The field of immunometabolism has made significant advances in elucidating the regulation of cellular metabolism on the phenotype and function of immune cells. Succinate is a metabolite of the tricarboxylic acid cycle that plays a critical role as a 'hormone-like' signaling molecule beyond its metabolic function. The macrophages (Mφ) are the hub for immune response, affecting the onset and progression of metabolic diseases associated with inflammation. The polarization of Mφ is shaped by metabolites, which contribute to various disease states and can even lead to metabolic dysfunction in tissues. Succinate has been demonstrated to regulate Mφ phenotype through several mechanisms, promoting or inhibiting inflammatory responses based on environmental factors. Consequently, it is regarded as a key regulator of Mφ function. This review aims to provide an overview of the most recent research on the modulation of Mφ phenotype by succinate-succinate receptor 1 (SUCNR1) axis in inflammatory and fibrotic diseases.

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.

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.

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.

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.

 In order to explore the efficacy of chemiluminescence immunoassay for the detection of Aspergillus IgG antibody, a method was established to enable the rapid detection of Aspergillus IgG antibody based on the indirect chemiluminescence principle with streptavidin magnetic particles as carrier, biotinylated Aspergillus galactomannan (GM) antigen as capture antigen, and alkaline phosphatase-labeled sheep anti-human IgG antibody as detection antibody. In addition, the assay performances of the method such as cut-off value, blank limit, detection limit, precision, interference test, cross-reactivity, methodological comparison, etc. were evaluated. The results showed that the detection efficacy of Aspergillus IgG antibody was performed favorably with a cut-off value of 120 AU/mL, a blank limit of 5.0 AU/mL and a detection limit of 5.2 AU/mL. The coefficients of variation of the reagent precision were <10%. The relative deviations of the test results for high concentrations of hemoglobin, bilirubin and triglyceride in the samples were less than 10%, and no cross-reactivity was observed. The data generated by this method was consistent with that of the ELISA kit (r=0.982, Kappa=0.87, P=0.00). Altogether, this study established a novel chemiluminescence-based immunoassay for the detection of Aspergillus IgG antibody, and the performance parameters of the assay system meet the clinical requirements and are suitable for the rapid detection of Aspergillus IgG antibody in serum.

In recent years, the prevalence of obesity has been steadily increasing, yet our understanding of the precise cellular and molecular mechanisms underlying obesity remains limited. The excessive accumulation of adipocytes during the process of obesity leads to a series of low-grade inflammation and has numerous effects on overall physiological function. This review focuses on the significant role of eosinophils in the progression of obesity and related metabolic disturbances, eosinophil generation and development, as well as their recruitment in adipose tissue (AT), and discusses the interaction between the microenvironment of AT and eosinophils. Understanding the detailed characteristics of eosinophils in the AT microenvironment will be beneficial for better exploiting their potential in the treatment of obesity.

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 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.

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.

Obesity-induced metabolic disorders, immune dysregulation, and metainflammation promote the pathogenesis and progression of chronic kidney disease (CKD). Apolipoprotein A IV (ApoA-IV) is a lipid-binding protein that regulates gluco-lipid metabolism and exhibits anti-inflammatory activity. However, the impact of ApoA-IV on the immune microenvironment of obesity-related chronic kidney inflammation remains insufficiently explored. This study employed the high-fat diet (HFD) to establish the HFD-induced obesity (DIO) model in both ApoA-IV knockout (ApoA-IV-/-/ApoA-IV KO) and wild type (WT) mice.The results showed that ApoA-IV KO exacerbated insulin resistance and renal lipid accumulation in DIO mice. Further analysis of the single-cell RNA sequencing (scRNA-seq) of kidney tissue and of immune cells revealed that ApoA-IV KO increased oxidative stress in macrophages, aggravated inflammations, impaired macrophage differentiation and polarization of M1- and M2-type phenotypes, reduced antigen processing，presentation and phagosome biological proceedings. Furthermore, ApoA-IV KO weakened the intercellular immune communication. It particularly downregulated the input signaling to macrophages, including pro-inflammatory IFN-II and TNF signaling, and the pro-proliferation and differentiation signaling including CSF and FLT3. Output signaling from macrophages were meanwhile downregulated, including immune-suppressive GALECTIN signaling, pro-resolving ANNEXIN signaling and immune-activating SPP1 signaling. Flow cytometry and bulk RNA sequencing of kidney tissue partially validated the scRNA-seq findings. This study highlights the critical role of ApoA-IV in regulating macrophage differentiation, functioning, oxidative stress, and inflammatory responses in the obese kidney, providing new insights for further exploration of the immune mechanisms underlying chronic kidney inflammation.

To investigate the effect of plumbagin (PL) on neuronal damage in epileptic rats by regulating adenosine-monophosphate-activated protein kinase (AMPK)/cAMP-responsive element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway, a rat epilepsy model was established by intraperitoneal injection of lithium chloride and pilocarpine. The model rats were randomly divided into model group, low-, medium- and high-dose PL groups (1, 5, and 10 mg/kg, respectively), and inhibitor group (10 mg/kg PL+20 mg/kg AMPK/CREB/BDNF signaling pathway inhibitor Compound C). Rats injected with the equal volume of physiological saline were set as control group. After successful modeling, each group received intraperitoneal injection of corresponding drugs, once a day for 21 consecutive days. The seizure status of rats in each group was evaluated according to the Racine grading standard; Brain waves of rats in each group were observed by electroencephalogram (EEG) and  Morris water maze experiment was applied to evaluate the cognitive and memorial functions. H-E staining was applied to observe the pathological damage of hippocampal tissues and TUNEL staining was applied to observe the apoptosis of rat neural cells. ELISA was applied to detect the levels of IL-6, IL-1β, and TNF-α in the hippocampus of rats in each group. Western blotting was used to detect the expression of proteins regarding the AMPK/CREB/BDNF signaling pathway in hippocampal tissues. Compared to those of the control group, the Racine grading, seizure frequency and duration of rats in the model group were all increased, along with the amplitude, total duration and frequency of the EEG waveform increased. The number of platform crossings and target quadrant activity time were reduced, and the escape latency prolonged. The rats hippocampal tissue structures were seriously damaged, neurons were loosely and badly arranged, with obvious edema and inflammatory cells infiltration. The apoptosis rate of neural cells, IL-6, IL-1β, and TNF-α levels were increased.  The expression levels of p-AMPK/AMPK, p-CREB/CREB, and BDNF proteins were significantly decreased (all with P＜0.05). Compared to those of the model group, the Racine grading, seizure frequency and duration of rats in the low-, medium-, and high-dose PL groups were decreased and the amplitude, total duration and frequency of the EEG waveform was decreased. The number of platform crossings and target quadrant activity time were increased, and the escape latency was shortened. The rats hippocampal structures damage was alleviated to certain extent, the cells were ordered, whose nuclear membrane was relatively clear, with few inflammatory cells infiltration. The apoptosis rate of neural cells, IL-6, IL-1β, and TNF-α levels were decreased. The expression levels of p-AMPK/AMPK, p-CREB/CREB, and BDNF proteins were significantly increased (all with P＜0.05). Compared to those of the high-dose PL group, the changes in the above indicators of rats in the inhibitor group were significantly reversed (all with P＜0.05). In conclusion, PL may activate the AMPK/CREB/BDNF signaling pathway, reduce neuronal apoptosis, inhibit inflammatory responses, and relieve neuronal damage in epileptic rats, thus exerting neuro-protective effects in epileptic rats.

In order to evaluate the effect of human mesenchymal stem cells with high expressions of both IL-18 and IL-12 on the in vitro expansion of NK cells from human peripheral blood, IL-18 and IL-12 high expression mesenchymal stem cells were constructed and used as feeding layers in activated culture flasks. PBMCs of healthy humans were collected and cultured in the activation flasks, and a cytokine induced culture protocol was used as the control. Growth curve of NK cell was statistically analyzed. Flow cytometry was used to analyze the proportion of NK cells and K562 cells were used as target cells to examine the in vitro killing ability of NK cells of the stem cell and the control groups. The results showed that the expansion efficiency of NK cells in the absolute ethanol fixed mesenchymal stem cell culture was the highest, and there was no significant difference in the expansion efficiency between the unfixed group and the control group. The purity of NK cells in the fixed group was the highest. The activation culture on day 0 had the highest amplification efficiency and purity, and there was no significant difference in cell purity between activation culture and the 2 activation cultures on day 0 and 5, but the expansion efficiency of NK cells decreased significantly after 2 activation cultures. The killing activity of the stem cell group on K562 tumor cells was significantly better than that of the control group.  Therefore, gene-edited mesenchymal stem cells can improve the in vitro expansion efficiency of NK cells derived from peripheral blood,increase the purity of flow cytometry results, promote the killing activity of NK cell on tumor. The cost of this protocol is lower in addition to being safer and more effective. 

This study aimed to investigate the expression levels of IL-18, IL-18 binding protein a (IL-18BPa), and IL-18 receptor α (IL-18Rα) in plasma CD4⁺ T cells and Th2 of patients with allergic rhinitis and asthma syndrome (ARA) and how allergen regulated their expressions. To this end, blood samples of ARA patients and healthy control subjects were collected, and the expression levels of IL-18, IL-18BPa, and IL-18Rα in CD4⁺ T cells and Th2 were determined by flow cytometry. Plasma levels of  total IL-18 (tIL-18) and total IL-18BPa (tIL-18BPa) were measured by ELISA, and the level of free IL-18 (fIL-18) was calculated. The level of IL-4 was examined by Bioplex system, and the correlations between fIL-18 and IL-4, and the percentage of Th2 were further analyzed. Our data showed that the proportions of IL-18⁺ cells in CD4⁺ T cells and Th2 were increased in ARA patients, and  house dust mite extract (HDME) induced rising IL-18 expression in Th2 of ARA patients. Plasma levels of IL-4, tIL-18, and fIL-18 were increased in ARA patients, and the level of fIL-18 was moderately correlated with levels of IL-4 and the proportion of Th2 in ARA patients. In conclusion, allergen may be involved in the pathogenesis of ARA by inducing elevated expression of IL-18 in Th2.

The study aims to investigate the serum soluble CD39 (sCD39) levels and explore its clinical significance in patients with hepatitis B-related liver diseases. A total of 134 patients with hepatitis B infection were selected for this study, including 46 patients with chronic hepatitis B (CHB), 56 patients with hepatitis B liver cirrhosis (HBLC), 32 patients with hepatocellular carcinoma (HCC), and additional 42 healthy controls (HC). The serum sCD39 levels were detected by ELISA. Additionally, the activities of aspartate transaminase (AST) and alanine transaminase (ALT) were measured by a biochemical analyzer. The expressions of serum AFP, hyaluronic acid (HA), and laminin (LN) were determined by the chemiluminescence method. qRT-PCR was employed to detect the HBV DNA content in serum. Furthermore, the liver fibrosis 4 factor (FIB-4) index, model for end-stage liver disease (MELD) score, AST-to-platelet ratio index (APRI), and modified PAGE-B (mPAGE-B) score were calculated. The differential expressions of serum sCD39 of HBV patients at different stages were measured and Spearman analysis was used to examine the correlation between sCD39 and various clinical indicators. The value of sCD39 in the diagnosis of HCC was evaluated by ROC curve analysis. The results showed that the sCD39 level in the HCC group was the highest and significantly different from that of all other groups (P<0.01). Importantly, the level of sCD39 in patients with liver injury（ALT＞40 U/L）was significantly higher than those without liver injury (ALT≤40 U/L, P<0.001). sCD39 was positively correlated with AST,ALT, AFP, LN, HA, APRI, FIB-4 index (P<0.001), and the MELD score (P=0.016). The AUC of serum sCD39 for the diagnosis of HCC was 0.743. The AUC of AFP combined with sCD39 was 0.894. The study suggests that sCD39 detection may be valuable for prognosis assessment in HBLC patients and for diagnosis of hepatitis B-related HCC. Therefore, sCD39 may serve as a potential diagnostic biomarker for HCC.

 The aim of this study is to investigate the impact of pachymic acid (PA) on inflammatory response in rats with chronic glomerulonephritis (CGN) by regulating monocyte chemoattractant protein 1(MCP-1)/CC chemokine receptor 2(CCR2) signaling pathway. Ten SD rats were randomly selected as the control group, and the rest were injected with cationic bovine serum albumin (C-BSA) to establish the CGN model. Successfully modeled rats were randomly divided into CGN group, PA group (10 mg/kg PA), GW0742 group (0.3 mg/kg GW0742), and PA+GW0742 group (10 mg/kg PA+0.3 mg/kg GW0742), with 10 rats in each group. 24-h urine protein, serum creatinine(Scr), blood urea nitrogen (BUN), antioxidant index and inflammatory index were detected with the corresponding commercial kits. The pathological injury of renal tissue was  detected by H-E staining, and the levels of IgG and C3 in glomerulus were detected by immunofluorescence staining. The mRNA expressions of MCP-1 and CCR2 were detected by qRT-PCR. Western blotting was used to detect the expressions of MCP-1/CCR2 signaling pathway related proteins. The results showed that rats in the control group had normal renal tissue whereas in the CGN group, both capillary rings and Bowman sacs were thickened, and degeneration of renal tubular epithelial cells and infiltration of inflammatory cells were observed. Compared to those of the control group, the levels of 24-h urine protein, Scr, and BUN, the levels of IL-1β and TNF-α, degree of renal tissue injury, fluorescence relative intensity of IgG and C3, and the mRNA and the protein levels of  MCP-1 and CCR2  in the CGN group significantly increased(P<0.05), while the levels of superoxide dismutase (SOD)and glutathione (GSH) significantly decreased (P<0.05). PA was shown to improve the above indicators, while GW0742 induced opposite changes of these indicators compared to those of the PA group. GW0742 attenuated the improvement effect of PA on inflammatory response in CGN rats. This study suggests that PA may improve the inflammatory response of CGN rats by down-regulating MCP-1/CCR2 signaling pathway.

The aim of this study was to explore the effect and possible mechanism of total flavonoids of rhizomadrynariae (TFRD) on endometrial damage and cell apoptosis in ovariectomized osteoporotic rats. Postmenopausal osteoporosis (PMOP) rat model was established by ovariectomy. The SD rats were randomly divided into 4 groups: the sham-operation group, the model group, the TFRD treatment group, and the positive drug (estradiol valerate) group. The latter two groups were daily gavaged with 108 mg/(kg·d) TFRD or 0.21 mg/(kg·d) estradiol valerate tablet from the 7th day after operation and treated for 12 weeks. H-E staining was used to observe the pathological morphology of rat femur and uterus tissues. Apoptosis of endometrial cells was evaluated by TUNEL staining. Western blotting was used to detect caspase-3 expression in uterus. ELISA was used to quantify levels of IL-6, TNF-α, and estradiol (E2) in the uterus tissues. Estrogen receptor alpha (ESR1) expression of uterus was detected by immunohistochemistry. Compared to the sham-operation group, the model group showed pathological injury of femur tissues and pathological changes in the uterus tissues. Apoptosis of endometrial cells was increased, along with elevated expressions of caspase-3, IL-6, and TNF-α, while the E2 and ESR1 expressions were decreased (all with P＜0.01). Compared to the model group, the TFRD, and positive drug treatment groups exhibited improved pathological changes in rat femur tissues and uterus. Apoptosis of endometrial cells and the protein levels of caspase-3, IL-6, and TNF-α were significantly decreased, while the expression levels of E2 and ESR1 were increased (all with P＜0.01). Therefore, TFRD can effectively alleviate endometrial injury and apoptosis in PMOP rats, and the mechanism may involve the regulation of E2 and the inhibition of the expression of inflammatory factors IL-6 and TNF-α.

To investigate the protective effect and underlying mechanism of ginkgolide B against trinitrobenzenesulfonic acid（TNBS）-induced ulcerative colitis (UC) in mice, this study used 60 specific pathogen free grade male C57BL/6 mice randomly divided into 6 groups: the control group, the UC model group, the ginkgolide B low-dose group (2.5 mg/kg), the ginkgolide B medium-dose group (5 mg/kg), the ginkgolide B high-dose group (10 mg/kg), and the sulfasalazine group (100 mg/kg). The UC model was established by slowly injecting TNBS solution into the mouse colon through a flexible catheter. The severity of UC was assessed by body weight, colon length, and disease activity index (DAI). Histological changes were observed by H-E staining and the expressions of inflammatory factors were detected by ELISA.The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were detected by corresponding activity measuring kits. The protein expressions of the TLR4/NF-κB pathway were detected by Western blotting. The results showed that, compared to the model group, mice in both the ginkgolide B medium- and high-dose groups showed less weight loss, longer colon length, lower DAI scores, significantly improved pathological damage of colitis, significantly lower expressions of TNF-α, IL-1β, IL-6, IL-2, and IL-12, significantly higher expression of IL-10, higher levels of SOD and GSH-Px, and lower levels of MDA. In addition, the activation of proteins in the TLR4/NF-κB pathway were inhibited. In summary, ginkgolide B has a significant protective effect on UC, and the mechanism may be related to the inhibition of the activation of TLR4/NF-κB signaling pathway.

In order to investigate the expression of long non-coding RNA (lncRNA) containing antisense RNA1 for 5 PH domains (FGD5-AS1) in hepatocellular carcinoma (HCC) tissues, its effects and mechanism on proliferation, migration, and invasion of HCC cells, HCC tissues and corresponding adjacent tissues of 53 HCC patients were collected.Human HCC cell lines (Hep3B, SK-HEP-1, MHCC97L, MHCC97-H, and Huh-7) and normal human hepatocytes (LO2) were cultured in vitro. RT-qPCR was used to detect the expression levels of lncRNA FGD5-AS1 and miR-512-3p in tissues and cell lines and the correlation between the expression levels of FGD5-AS1 and miR-512-3p in HCC patients' cancer tissues were analyzed by Pearson correlation test.Western blotting was used to detect the expression of Cyclin D1 protein. HCC cell line Huh-7 was cultured in vitro, and was transfected with FGD5-AS1 small-interfering RNA (siRNA) or miR-512-3p mimic, respectively, or co-transfected with FGD5-AS1 siRNA and miR-512-3p inhibitor. The proliferation, migration, and invasion of cells in each group were detected by CCK8 assay, cell cloning experiment and Transwell assay, respectively. The dual-luciferase reporter gene experiment was used to verify the binding between FGD5-AS1 and miR-512-3p or miR-512-3p and Cyclin D1. FGD5-AS1 knockdown (KD) Huh-7 cells were subcutaneously inoculated into nude mice to observe tumor growth. The results showed that compared to those of the adjacent tissues, the protein expressions of FGD5-AS1 and Cyclin D1 were increased in HCC tissues (both P＜0.05), while the expression of miR-512-3p was decreased (P＜0.05). There was a significant negative correlation between FGD5-AS1 and miR-512-3p levels in HCC tissues (r=-0.856, P＜0.01). Compared to those of the LO2 cells, the protein expressions of FGD5-AS1 and Cyclin D1 in human HCC cell lines (Hep3B, SK-HEP-1, MHCC97L, MHCC97-H, and Huh-7) were all increased, while the expression level of miR-512-3p was decreased (all with P＜0.05). FGD5-AS1 KD or over-expression of miR-512-3p reduced the proliferative activity, number of colony formation, migration, and invasion of Huh-7 cells (all with P＜0.05). FGD5-AS1 targeted miR-512-3p, and the expression of miR-512-3p was increased in Huh-7 cells upon FGD5-AS1 KD (P＜0.05). Cyclin D1 was the target gene of miR-512-3p, and the expression of Cyclin D1 protein was decreased in Huh-7 cells overexpressing miR-512-3p (P＜0.05). Down-regulation of miR-512-3p reversed the inhibition of FGD5-AS1 KD on Huh-7 cells proliferation, migration, invasion, and Cyclin D1 expression. Xenografted nude mice result demonstrated that FGD5-AS1 KD inhibited the growth of Huh-7 cells in vivo. In conclusion, lncRNA FGD5-AS1 is highly expressed in HCC tissues and FGD5-AS1 KD inhibits the proliferation, migration, and invasion of Huh-7 cells by targeting the miR-512-3p/Cyclin D1 axis. 

The aim of this study was to prepare a monoclonal antibody targeting the P2 substructural domain of the GⅡ.17 type norovirus (NV) using recombinant protein immunization-hybridoma technique, and to characterize its biological properties. The purified recombinant antigen GⅡ.17-P2 was used to immunize BALB/c female mice, followed by cell fusion of SP2/0 and splenocytes from the immunized mice using the hybridoma technique. A specific antibody positive hybridoma cell line was selected for the production and purification of the monoclonal antibody specific to the substructural domain of the P2 region of GⅡ.17 NV. The biological characteristics of the monoclonal antibody were subsequently evaluated by indirect ELISA, Western blotting, and dot-ELISA assays. Additionally, the sequences of the variable regions of the monoclonal antibody were examined by semi-nested PCR. The results showed that a total of 23 positive hybridoma cell lines were acquired, with a positivity rate of 23.96%. A cell line stably secreting the monoclonal antibody specific to GⅡ.17 type NV P2 domain, named G10, was obtained by subcloning and other techniques. G10 monoclonal antibody was prepared from ascites by antibody purification. The G10 monoclonal antibody had a titer of up to 10-5 μg/mL, a sensitivity of 10-5 μg/mL for antigen detection by means of ELISA, and can recognize the wild-type GⅡ.17 NV. The sequence characteristics of the variable regions of the G10 monoclonal antibody were also elucidated. In brief, monoclonal antibody targeting the P2 substructural domain of GⅡ.17 NV has been successfully developed by the recombinant protein immunization-hybridoma technology, laying the foundation for the development of rapid diagnostic reagents against GⅡ.17 type NV.

This study aimed to explore the potential mechanism of Nandan bamboo in the treatment of gouty arthritis (GA) by combining network pharmacology and experimental research. Procedures: (1) The pharmacological active ingredients of Nandina domestica Thunb were identified by literature review. The corresponding drug targets were explored by SwissTarget and TargetNet databases. OMIM and GeneCards databases were used to screen for GA disease-related targets. The overlapping targets of the two analyses were imported into the STRING platform for protein-protein interaction (PPI) network analysis to find out the core targets. Cytoscape 3.10.1 software was used to draw the “disease-drug-pathway-target” network to screen for the key active ingredients of Nandina domestica Thunb for the treatment of GA. GO function and KEGG pathway enrichment analysis were performed using online bioinformatics analysis and visualization cloud platform. (2) GA inflammatory cell model was established by stimulation of THP1-derived macrophages using LPS in combination with monosodium urate (MSU). Cells were coincubated with different concentrations of drugs for 24 h. CCK8 assay was used to detect the cell toxicity of Nandina domestica Thunb extract and ELISA was used to detect the IL-1β level in supernatant. RT-qPCR was used to detect the expressions of TLR2/NF-κB signaling pathway related genes and the relative expression of NLRP3 mRNAs. Western blotting was used to detect the NF-κB, NLRP3, and IL-1β protein expressions. The results showed that (1) A total of 309 drug interacting targets, 776 disease-related targets, and 30 common targets were identified. The key bioactive molecules included caffeic acid and biapigenin, and the core disease targets included TNF, PTGS2, RELA (NF-κB p65), SIRT1, and SYK. The key targets were mainly involved in inflammatory signaling pathways such as NF-κB pathway and NOD-like receptor pathway; (2)The CCK8 assay showed that the concentration of Nandina domestica Thunb had no significant effect on cell viability at 37.5, 75 or 150 μg/mL. Compared to those of the control group, the IL-1β level in the cell supernatant, the mRNA expressions of TLR2, myeloid differentiation factor 88 (MYD88), TNF receptor-associated factor 6 (TRAF6), TGF-β-activated activated kinase 1 (TAK1), inhibitor α of κB kinase (IKKα), NF-κB, NLRP3, and IL-1β, and the protein expressions of NF-κB, NLRP3, and IL-1β in the model group were significantly increased (all with P＜0.05). Compared to those of the model group, the level of IL-1β in the cell supernatant, the mRNA expressions of TLR2，MYD88，TRAF6，TAK1，IKKα，NF-κB，NLRP3  and IL-1β, and the protein expressions of NF-κB, NLRP3, and IL-1β in the Nandina domestica Thunb extract treated groups were all significantly decreased（all with P＜0.05）. In conclusion, Nandina domestica Thunb extract can reduce the production and release of inflammatory factors through regulating the TLR2/NF-κB signaling pathway and inhibiting the activation of NLRP3 inflammasome, making it a treatment for GA.

Single-cell RNA sequencing (scRNA-seq) is a novel technigue for high-throughput sequencing analysis of the whole transcriptome to elucidate the gene status of monocells. It is an important research method to investigate the heterogeneity of cells and the underlying mechanisms as well as help to identify novel cell subpopulations. In addition, it provides insight into the molecular underpinnings of disease pathogenesis, evolution, and drug resistance. This technology has quickly developed in recent years and has accumulated a significant amount of research data. This review summarizes the advances of scRNA-seq  and its usage on autoimmune diseases in order to provide a theoretical framework for the application of this technology in immunology and  related fields as well as diagnosis and management of diseases.

The objective of this study was to verify the performance of time-resolved fluorescence immunoassay for human serum anti-phospholipase A2 receptor antibody IgG4 (PLA2R-IgG4) including the linear range, accuracy, precision, specificity, and performance of PLA2R-IgG4 reagent with magnetic particle time-resolved fluorescence immunoassay. The results showed that the blank limitation was 7.02 ng/mL, linear range was 50.00 ng/mL-10 000.0 ng/mL, accuracy was 86.28%-104.58%, intra-batch precision was 2.62%-5.33%, inter-batch precision was 7.37%-8.26%, and the specificity was in acceptable range. The detection rate of PLA2R-IgG4 in 77 idiopathic membranous nephropathy patients was 75.32%, and the test results of 15 patients with secondary membranous nephropathy were all negative. All the indexes of this method meet the requirements of clinical test quality, and this method shows a better detection rate for idiopathic membranous nephropathy, making it promising in clinical translation. 

To investigate the role of HS1-associated protein X-1 (HAX-1) in lupus nephritis (LN) patients, 50 patients with SLE were selected as the study objects, and 29 healthy patients were selected as the control group. qRT-PCR was used to detect the mRNA expression of HAX-1  in PBMC. The expression of HAX-1 in kidney tissue was detected by immunohistochemistry (IHC). The proportions of CD4⁺ CD25⁺ Foxp3⁺ Treg and CD4⁺ IL-17A⁺ Th17 in peripheral blood were measured by flow cytometry. Human renal mesangial cells (HRMC) were cultured in vitro, and HAX-1 silencing plasmid and HAX-1 overexpression plasmid were transfected. Flow cytometry and MTT were used to measure the apoptosis and proliferation of HRMC after transfection, respectively. Western blotting was used to detect the expressions of proliferation-related signal PI3K/Akt and apoptosis-related signal Bax/Casepase-9. The results showed that the mRNA expression level of HAX-1  in PBMC of the active LN group was significantly higher than that of the NRA-SLE group (P<0.001). Meanwhile, HAX-1  mRNA  expression level was positively correlated with SLE disease activity index (SLEDAI-2K) and 24 h urinary protein quantity in peripheral blood (R2= 0.876, P<0.001; R2=0.409, P<0.001). The IHC results showed that the expression level of renal HAX-1 in the active LN group was significantly higher than that of the normal control group (P<0.001). The expression level of HAX-1 in renal tissue was positively correlated with LN activity score and chronicity score (r=0.975, P<0.001; r=0.667, P=0.002). Overexpression of HAX-1 reduced apoptosis (P<0.001) and increased the proliferation activity of HRMC (P<0.001). Meanwhile, the levels of PI3K and p-Akt significantly increased (P<0.001) while the levels of Bax/Casepase-9 significantly decreased (P<0.001). In contrast, upon transfection of HAX-1 silencing plasmid, the apoptosis of HRMC was significantly increased (P<0.001), and the proliferation activity was significantly reduced (P<0.001), along with significantly reduced PI3K and p-Akt expression (P<0.001), increased Bax/Casepase-9 expression(P<0.001). These results suggest that HAX-1 expression in peripheral blood and kidney tissues of patients with active LN group is closely related to kidney involvement and disease activity, as well as the imbalance of the CD4⁺ IL-17A⁺ Th17 and CD4⁺ CD25⁺ Foxp3⁺ Treg. Using a system of HRMC cultured in vitro, this study demonstrates that HAX-1 can promote the pathogenesis  of glomerular nephritis in LN by affecting the signaling pathways related to mesangial cell proliferation and apoptosis. HAX-1 may have a dual effect on Th17/Treg balance and HRMC proliferation, contributing to the pathogenesis of LN. 

Alzheimer's disease (AD) is a slowly progressing and hard to diagnose degenerative disease of the central nervous system. Its pathological characteristics and pathogenesis are very complex, mainly involving amyloid-β peptide (Aβ) deposition,Tau protein hyperphosphorylation, neuroinflammation and many other aspects. In recent years, it has been found that lipocalin-2  (Lcn2), an inflammatory protein involved in immune regulation and iron ion transportation, directly or indirectly promotes brain neuroinflammation, iron accumulation and blood-brain barrier function damage in the development of AD. From the above aspects, this review summarizes the relationship between Lcn2 and AD.

The aim of this study is to explore the regulatory features, co-regulatory roles and effects on the epigenome of the STAT family proteins and the master transcription factors of the Th1, Th2, and Th17 subtypes, including the T-box expressed in T cell (T-bet), GATA binding protein 3 (GATA3), and retinoic acid receptor-related orphan receptor γt (RORγt) in Th differentiation. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) data of different T cell differentiation stages and chromatin immunoprecipitation sequencing (ChIP-seq) data of transcription factors were obtained and integrated from the GEO database. The co-localization, the genomic distribution of the transcription factors, and the chromatin accessibility changes during differentiation and functions of regulated genes were analyzed. The results showed that the transcription factor STAT2 was the main STAT family transcription factor involved in the maintenance of Th0 chromatin characteristics. STAT4 was widely co-localized with T-bet and regulated Th1 activation. The master regulator GATA3 and the co-factor STAT6 preferentially bound to non-promoter cis-elements thereby directing Th2 differentiation. RORγt, the master transcription factor, enhanced the binding strength of STAT3 and STAT5 in a distinctive manner independent of altered chromatin accessibility, co-regulating Th17-specific differentiation. This study suggests that STAT family transcription factors selectively participate in and differentially regulate Th differentiation.

This study aimed to evaluate the performance and property of a fully automated ultra-high speed immunoassay system based on high-throughput flow fluorescence technology for detecting autoimmune antibodies in clinical laboratories. According to the laboratory accreditation guidelines issued and implemented by the China National Accreditation Commission for Conformity Assessment (CNAS), flow fluorescence technology was used to detect the autoantibodies and evaluations  were made on parameters including the precision, linear range, accuracy, and limit of blank (LOB). When conducting repeatability validation on quality control products at both low and high concentrations, the average standard deviation and coefficient of variation (CV)  were calculated of each antibody level in the 16 antibody profiles. The CV of all antibodies were lower than 7% and 5%, respectively, which were within the less than 10% range as declared by the manufacturer. The first-order polynomial linear regression coefficients for resistance to anti-C1q-Ab and resistance to anti-dsDNA-Ab were 0.999 and 0.996, respectively, with correlation coefficient  above 0.999. The deviation distributions were all within 3% and the results of the 2 recovery experiments were 91.56% and 105.60%, respectively. When Oumeng company imprinting method was used as a reference, the compliance rates of the validation projects were all above 92%. Values of LoB for anti-C1q-Ab and anti-dsDNA-Ab were both within 0.5 U/ml and 3 IU/ml, respectively. In conclusion, all performance parameters of the flow cytometry fluorescence technology for autoantibody detection are consistent with the manufacturer's specifications and pass the standard of clinical requirements. It can replace similar imported instruments.

Inflammatory bowel disease (IBD) is a chronic relapsing intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn's disease (CD). Although the etiology of IBD remains unknown, it is well accepted that factors including heredity, intestinal environment, bacterial infection and dysregulated immunity may contribute to the onset. A number of guidelines in China and abroad have pointed out that basal plasmacytosis is an important pathological indicator of IBD diagnosis, and the aggregation value of plasma cells in the middle and lower mucosa is much higher than that of other lymphocytes. It was also observed that plasma cell aggregation disappeared in the intestinal tissue of IBD patients in remission after treatment with biologics. Therefore, it is speculated that the B cell-plasma cell axis in humoral immunity is an important path in the pathophysiology of IBD. However, the underlying mechanism remains unclear. This review summarizes the progress on the roles of humoral immunity of the intestinal mucosa in the pathogenesis of IBD.

The purpose of this study is to explore the role and mechanism of peptidyl arginine deimidase type 4 (PAD4) in inflammatory adipose tissue. The subcutaneous and visceral adipose tissues of db/db (type 2 diabetes mellitus [T2DM] group), db/m (T2DM control group), ob/ob (obese group) and ob/c(obese control group) were extracted, and the expression of PAD4 in subcutaneous and visceral adipose tissue of T2DM and obese mice was detected by immunohistochemistry. Wild-type mouse primary peritoneal macrophages and mouse macrophage cell line RAW264.7 were stimulated with LPS, the expressions of PAD4, inflammatory factors TNF-α and IL-6, the activation of NF-κB signal pathway in the 2 types of cells were detected by qRT-PCR and Western blotting, respectively. The results showed that compared to those of the db/m and ob/c groups, the expression of PAD4 in subcutaneous and visceral adipose tissue, primary peritoneal macrophages and RAW264.7 cells stimulated by LPS in db/db and ob/ob groups were all decreased, while the expressions of inflammatory factors TNF-α and IL-6 increased significantly.Meanwhile, the TLR4/NF-κB signal pathway was activated. This study shows that the expression of PAD4 is decreased in subcutaneous and visceral adipose tissue in inflammatory state (T2DM and obesity) and is negatively correlated with the activation of the TLR4/NF-κB signal pathway.

Acute myeloid leukemia (AML) is a malignant hematological disease characterized by the clonal proliferation of myeloid progenitor cells and high heterogeneity. The development and progression of AML are closely associated with alterations in T cell phenotype and function. These changes can lead to aberrancies in the T cell population, ultimately resulting in immune dysfunction ofthe body. In recent years, researchers have utilized the anti-tumor activity of T cells in the treatment of AML, and it has been observed that the functional recovery of T cells in patients exerts a pronounced inhibitory effect on leukemia cells. At present, T cell immunotherapy for AML includes tumor infiltrating lymphocyte (TIL) therapy, bispecific antibody-recruited T cell therapy, immune checkpoint inhibitor (ICI) therapy, chimeric antigen receptor T-cell (CAR-T) therapy, and tumor-specific receptor gene-transduced T cell (TCR-T) therapy. This review comprehensively summarizes recent domestic and international advancements in T cell immunotherapy research, offering anoverview of the therapeutic efficacy and mechanisms of T cell immunotherapy on AML. The objective is to elucidate new potential strategies for the clinical treatment of AML.

To explore the protective effect of miR-34b-5p on sepsis induced acute lung injury (ALI) in rats and its impact on the phosphatase and tensin homolog (PTEN)/Akt/mTOR pathway, 80 specific pathogen free grade male SD rats were randomly divided into the sham group, the model group, the empty vector group, and the miR-34b-5p group, with 20 rats in each group. The rats in the sham group only underwent laparotomy, while the remaining rats were subjected to cecal ligation and perforation to establish a sepsis model. After the establishment of the model, rats in the empty vector group and the miR-34b-5p group were injected with empty vectors and miR-34b-5p overexpression plasmids through the tail vein, respectively. Rats in the model group and the sham group were injected with equal amount of physiological saline. Three days after injection, ELISA was used to determine the IL-1β and IL-6 levels in rat peripheral blood. The wet weight/dry weight  (W/D）ratio of rat lung tissue was calculated and the pathological changes of rat lung tissue was observed by H-E staining. The apoptosis of lung histiocyte cells was detected by TUNEL method. miR-34b-5p, IL-1β and IL-6 mRNA levels in lung tissue were detected by qRT-PCR. Western blotting was used to detect the protein levels of PTEN, p-Akt, p-mTOR, Akt, mTOR, B cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase-3. The results showed that the alveoli in the sham group appeared normal, while those of the model group and the empty vector group were collapsed, along with thickened alveolar walls, vascular congestion, pulmonary interstitial congestion, edema, and inflammatory cell infiltration. The infiltration of inflammatory cells in the lung tissue of rats in the miR-34b-5p group was reduced, and alveolar injury was significantly improved. Compared to those of the sham group, the expressions of IL-1β and IL-6 at both protein and mRNA levels, the number of apoptotic cells, levels of Bax, Caspase-3 and PTEN as well as W/D ratio were significantly increased in the model group (P<0.01), while the levels of miR-34b-5p, Bcl-2 protein, p-Akt/Akt ratio, and p-mTOR/mTOR ratio were significantly decreased (P<0.01). Compared to those of the empty vector group, the miR-34b-5p expression, Bcl-2 protein level, p-Akt/Akt and p-mTOR/mTOR ratio in the lung tissue of the miR-34b-5p group were significantly increased (P<0.01), while the IL-6, IL-1β protein and mRNA levels, the number of apoptotic cells, the Bax, PTEN, Caspase-3 protein levels, and W/D ratio were significantly decreased (P<0.01). This study suggests that miR-34b-5p alleviates pulmonary inflammation and cell apoptosis of ALI in sepsis rats through the PTEN/Akt/mTOR pathway.

A special defense mode of neutrophils has been found in recent years, i.e. the neutrophil extracellular trap (NET), which can resist the invasion of pathogens to a certain extent. However, excessive amount of NET will cause pathological inflammation and immune disorders. Studies have confirmed that NET is highly correlated with the imbalance of adaptive immune cells and plays an important role in adaptive immunity. This review briefly summarizes the composition, formation mechanisms, and functional detection of NET, and focuses on the research progress on the relationship between NET and adaptive immune cell imbalance. This review will promote a clear understanding of NET and provide a theoretical basis for revealing the pathogenesis of related diseases, developing disease monitoring and treatment protocols, as well as identifying therapeutic targets.

Chronic skin wound healing is one of the challenges in the field of repairing. Macrophages play an important modulatoryrole in wound healing and they may polarize to M1 or M2 phenotypes in different microenvironments and upon various stimuli. Dysregulation of the macrophage phenotypes is a vital factor in chronic skin wound healing, and correction of the macrophage phenotypes can promote wound healing. This review summarizesthe origin of skin macrophages, the polarization of macrophages, the mechanism and strategy to regulate macrophages polarization and promote skin chronic wound healing in order to provide evidence for skin chronic wound healing.

This study aimed to investigate the effect of Bupiqiangli compound on Th17/Treg differentiation of thymic lymphocytes in rats with myasthenia gravis. CCK-8 was used to determine an optimal 10% serum concentration for subsequent experiments. Cells were divided into 8 groups: the normal group (control), the normal+blank serum group (control+BS), the myasthenia gravis model group (model), the myasthenia gravis model+blank serum group (model+BS), the myasthenia gravis model+low-dose Bupiqiangli compound treatment serum group (model+LBPQL), the myasthenia gravis model+medium-dose Bupiqiangli compound treatment serum group (model+MBPQL), the myasthenia gravis model+high-dose Bupiqiangli compound treatment serum group (model+HBPQL), and the myasthenia gravis model+prednisone containing serum group (model+prednisone). After treated with serum for 24 hours, the proportions of Th17 and Treg cells in each group were detected by flow cytometry. ELISA was used to detect the content of IL-17 and TGF-β in the supernatant. Western blotting was used to measure the protein levels of Notch1, Hes1, Hes5 and Hey1. The results showed that, compared to that of the spleen deficiency model group, the proportion of Th17 cells in the model+HBPQL group and the model+Prednisone group decreased significantly (P<0.05), while the proportion of Treg cells increased significantly (P<0.05). The expression of IL-17 was significantly decreased (P<0.05), while the expression of TGF-β was significantly increased (P<0.05). The protein expressions of Notch1, Hes1, Hes5, and Hey1 were significantly decreased (P<0.05). The results indicate that Bupiqiangli compound can regulate the proportions of Th17 and Treg in thymic lymphocytes in rats with myasthenia gravis. The underlying mechanism may involve the regulation of the Notch signaling pathway. 

Obesity is the excessive accumulation of fat caused by the imbalance between energy intake and expenditure, which has become a global health issue. The metabolic homeostasis of adipose tissue plays a crucial role in the progression of obesity and has numerous impacts on systemic physiology. Studies have found that various immune cells and cytokines are involved in maintaining and regulating the metabolic homeostasis of adipose tissue, suggesting the significant potential of immune cells in alleviating obesity and insulin resistance (IR). From the perspectives of innate and adaptive immunity, this review discusses the progress on the role of immune cells in thermogenesis and metabolic functions of adipose tissue and further explores the therapeutic potential of the immune system in obesity and related metabolic disorders.

Hepatocellular carcinoma (HCC) is one of the most common malignancies, and the main risk factor for HCC is HBV infection. Hepatitis B virus X protein (HBx) is a key regulator of HBV-associated HCC and can promote tumorigenesis. It has been reported that many long non-coding RNA (lncRNA) contribute to the HCC development, mainly by promoting HBV replication, up-regulating oncogenes expression, or down-regulating the expression of tumor suppressors.Some lncRNA can also act directly as tumor suppressors, which have been extensively studied as disease-treating targets.In this review, we will discuss the role of HBx-regulated lncRNA in HBV-induced HCC and summarize the mechanisms of tumorigenesis and the development of cancer.