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Maternal tolerance to semi- or fully allograft conceptus is a prerequisite for the maintenance of pregnancy. Once this homeostasis is disrupted, it may result in pregnancy loss. As a potential approach to prevent pregnancy loss, targeting decidual immune cells (DICs) at the maternal-fetal interface has been suggested. Although the phenotypic features and functions of DIC have been extensively profiled, the regulatory pathways for this unique immunological adaption have yet to be elucidated. In recent years, a pivotal mechanism has been highlighted in the area of immunometabolism, by which the changes in intracellular metabolic pathways in DIC and interaction with the adjacent metabolites in the microenvironment can alter their phenotypes and function. More inspiringly, the manipulation of metabolic profiling in DIC provides a novel avenue for the prevention and treatment of pregnancy loss. Herein, this review highlights the major metabolic programs (specifically, glycolysis, ATP-adenosine metabolism, lysophosphatidic acid metabolism, and amino acid metabolism) in multiple immune cells (including decidual NK cells, macrophages, and T cells) and their integrations with the metabolic microenvironment in normal pregnancy. Importantly, this perspective may help to provide a potential therapeutic strategy for reducing pregnancy loss via targeting this interplay.

Interleukin-17 (IL-17) is known as a Th17-cell-derived proinflammatory cytokine, which plays a pivotal role in several inflammatory and autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and psoriasis. Emerging evidence has shown that IL-17 is linked to endometriosis, although the etiology of endometriosis is still unknown. The IL-17 expression is up-regulated in serum, peritoneal fluid (PF) and endometriotic lesions from patients with endometriosis but the related regulation mechanisms are complex and obscure. Meanwhile, the specific roles of IL-17 in endometriosis are also worthy of further exploration. Through the integration and summary of literature, we conclude that the secretion of IL-17 increases under the regulation of ectopic microenvironment and other factors, and then IL-17 is deeply involved in endometriosis in the regulation of immune microenvironment, the invasion and growth of ectopic lesions, and so on, which implies its therapeutic value in this disorder.

In some cases of spontaneous miscarriage (SM), the exact etiology cannot be determined. Autophagy, which is responsible for cellular survival under stress conditions, has also been implicated in many diseases. Recently, it is also surmised to be correlated with SM. However, the detailed mechanism remains elusive. In fact, there are several essential steps during pregnancy establishment and maintenance: trophoblasts invasion, placentation, decidualization, enrichment and infiltration of decidua immune cells (e.g., natural killer, macrophage and T cells). Accordingly, upstream molecules and downstream effects of autophagy are discussed in these processes, respectively. Of note, autophagy regulates the crosstalk between these cells at the maternal-fetal interface as well. Aberrant autophagy is found in villi, decidual stromal cells, peripheral blood mononuclear cells in SM patients, although the findings are inconsistent among different studies. Furthermore, potential treatments targeting autophagy are included, during which rapamycin and vitamin D are hot-spots in recent literatures. To conclude, a moderately activated autophagy is deeply involved in pregnancy, suggesting that autophagy should be a regulator and promising target for treating SM.

A successful pregnancy requires sufficient decidualization of endometrial stromal cells (ESCs). CD82, a metastasis suppressor, is a critical regulator for trophoblast invasion but the effect in decidualization was largely unknown. Here we reported that there was a high level of CD82 in DSC by the immunohistochemistry staining and flow cytometer analysis. Stimulation with prostaglandin E2 (PGE2) elevated the expression of CD82 in ESCs. In contrast, celecoxib, a selective COX-2 inhibitor, significantly downregulated the expression of CD82 in decidual stromal cells (DSCs). Bioinformatics analysis and further research showed that recombinant human interleukin (IL)-1β protein (rhIL-1β) upregulated CD82 in ESCs. Of note, blocking IL-1β signaling with anti-human IL-1β neutralizing antibody could reverse the stimulatory effect of PGE2 on CD82 in ESCs. Silencing CD82 resulted in the decease of the decidualization markers PRL and IGFBP1 mRNA levels in DSCs. More importantly, we observed rhIL-1β also upregulated the expression of COX-2, and the upregulation of PRL and IGFBP1 induced by rhIL-1β could be abolished by celecoxib in ESCs or CD82 deficiency in DSCs. This study suggests that CD82 should be a novel promotor for decidualization under a positive regulation of the COX-2/PGE2/IL-1β positive feedback loop.

Background: Patients with endometriosis (EMs) have high risks of infertility and spontaneous abortion. How to remodel the fertility of patients with EMs has always been the hot spot and difficulty in the field of reproductive medicine. As an aglycone of ginsenosides, protopanaxadiol (PPD) possesses pleiotropic biological functions and has high medicinal values. We aimed to investigate the effect and potential mechanism of PPD in the treatment of EMs-associated infertility and spontaneous abortion. Methods: The EMs mice models were constructed by allotransplantation. The pregnancy rates, embryo implantation numbers and embryo resorption rates of control and EMs were counted. RNA sequencing, qRT-PCR, enzyme linked immunosorbent assay (ELISA) and FCM analysis were performed to screen and confirm the expression of endometrial receptivity/decidualization-related molecules, inflammation cytokines and NK cell function-related molecules in vitro and/or in vivo. The SWISS Target Prediction, STRING and Cytoscape were carried out to predict the potential cellular sensory proteins, the protein-protein interaction (PPI) network between sensory proteins and fertility-related molecules, respectively. Micro-CT detection, liver and kidney function tests were used to evaluate the safety. Results: Here, we observe that PPD significantly up-regulates endometrial receptivity-related molecules (e.g., Lif, Igfbp1, Mmps, collagens) and restricts pelvic inflammatory response (low levels of IL-12 and IFN-γ) of macrophage, and further remodel and improve the fertility of EMs mice. Additionally, PPD increases the expression of decidualization-related genes and Collagens, and promotes the proliferation, residence, immune tolerance and anagogic functions of decidual NK cells (low levels of CD16 and NKp30, high levels of Ki67, VEGF, TGF-β) in pregnant EMs mice, and further triggers decidualization, decidual NK cell-mediated maternal-fetal immune tolerance and angiogenesis, preventing pregnant EMs mice from miscarriage. Mechanically, these effects should be dependent on ESRs, PGR and other sensory proteins (e.g., AR). Compared with GnRHa (the clinic first-line drug for EMs), PPD does not lead to the decline of serum estrogen and bone loss. Conclusion: These data suggest that PPD prevents EMs-associated infertility and miscarriage in sex hormones receptors-dependent and independent manners possibly, and provides a potential therapeutic strategy with high efficiency and low side effects to remodels the fertility of patients with EMs.

Menstruation occurs in few species and involves a cyclic process of proliferation, breakdown and regeneration under the control of ovarian hormones. Knowledge of normal endometrial physiology, as it pertains to the regulation of menstruation, is essential to understand disorders of menstruation. Accumulating evidence indicates that autophagy in the endometrium, under the regulation of ovarian hormones, can result in the infiltration of immune cells, which plays an indispensable role in the endometrium shedding, tissue repair and prevention of infections during menstruation. In addition, abnormal autophagy levels, together with resulting dysregulated immune system function, are associated with the pathogenesis and progression of endometriosis. Considering its potential value of autophagy as a target for the treatment of menstrual-related and endometrium-related disorders, we review the activity and function of autophagy during menstrual cycles. The role of the estrogen/progesterone-autophagy-immunity axis in endometriosis are also discussed.

Aspirin, one of the most widely applied medicines, not only possesses the effects on reducing fever, anti-vascular hyperplasia, and anti-inflammation, but also has the capacity of preventing platelet aggregation. So far, it is acceptable to adopt aspirin, especially low-dose aspirin (LDA), to prevent pregnancy-related complications, such as pregnancy complicated by antiphospholipid syndrome, systemic lupus erythematosus, or preeclampsia; unexplained recurrent spontaneous abortion; fetal growth restriction; and preterm birth. In this article, we reviewed the possible mechanism of action and applications of aspirin in these pregnancy-related complications.

The survival and development of a semi-allogenic fetus during pregnancy require special immune tolerance microenvironment at the maternal fetal interface. During the establishment of a successful pregnancy, the endometrium undergoes a series of changes, and the extracellular matrix (ECM) breaks down and remodels. Collagen is one of the most abundant ECM. Emerging evidence has shown that collagen and its fragment are expressed at the maternal fetal interface. The regulation of expression of collagen is quite complex, and this process involves a multitude of factors. Collagen exerts a critical role during the successful pregnancy. In addition, the abnormal expressions of collagen and its fragments are associated with certain pathological states associated with pregnancy, including recurrent miscarriage, diabetes mellitus with pregnancy, preeclampsia and so on. In this review, the expression and potential roles of collagen under conditions of physiological and pathological pregnancy are systematically discussed.

To explore the effect ofA total of 120 cases of cesarean section women were randomly divided into an observation group and a control group, 60 cases in each group. The control group was treated with routine nursing. On the basis of the control group, the observation group was treated with oral administration ofThe onset time of lactation in the observation group was earlier than that in the control group (

During the implantation of embryo, apoptosis is inevitable. These apoptotic cells (AC) are removed by efferocytosis, which fills the macrophage with a metabolite load nearly equal to the phagocyte itself. A timely question pertains to the interrelationship between efferocytosis metabolism and the immune behavior of decidual macrophages (dMΦs) and its effect on pregnancy outcome. Here we report a positive feedback of IL-33/ST2-AXL-efferocytosis leading to pregnancy failure through metabolic reprogramming of dMΦs. We compared the serum level of IL-33, sST2, along with IL-33, ST2, efferocytosis and metabolism of dMΦs from both normal gravidas and unexplained recurrent pregnancy loss (RPL) patients. And we revealed the disturbance of IL-33/ST2 axis, increased apoptotic cells and elevated efferocytosis of dMΦs from the patients with RPL. Afterwards the dMΦs swallowing so many apoptotic cells secreted more sST2 and less TGF-β, which polarized dMΦs towards M1 phenotype. Moreover, the elevated sST2 biased the efferocytosis metabolism of RPL dMΦs towards oxidative phosphorylation and exacerbated the disruption of IL-33/ST2 signaling pathway. The metabolic disorders also led to the dysfunction of efferocytosis, resulting in more uncleared apoptotic cells and the secondary necrosis occurred. We also screened efferocytotic molecule AXL regulated by IL-33/ST2. This positive feedback of IL-33/ST2-AXL-efferocytosis led to pregnancy failure. And the IL-33 knockout mice demonstrated poor pregnancy outcomes, and exogenous supplementation of mouse IL-33 could partially alleviate the fate of embryo losses. These findings highlight a new etiological mechanism whereby dMΦs leverage immunometabolism for the homeostasis of microenvironment at the maternal-fetal interface.

During embryo implantation, apoptosis is inevitable. These apoptotic cells (ACs) are removed by efferocytosis, in which macrophages are filled with a metabolite load nearly equal to the phagocyte itself. A timely question pertains to the relationship between efferocytosis-related metabolism and the immune behavior of decidual macrophages (dMΦs) and its effect on pregnancy outcome. Here, we report positive feedback of IL-33/ST2-AXL-efferocytosis leading to pregnancy failure through metabolic reprogramming of dMΦs. We compared the serum levels of IL-33 and sST2, along with IL-33 and ST2, efferocytosis and metabolism of dMΦs, from patients with normal pregnancies and unexplained recurrent pregnancy loss (RPL). We revealed disruption of the IL-33/ST2 axis, increased apoptotic cells and elevated efferocytosis of dMΦs from patients with RPL. The dMΦs that engulfed many apoptotic cells secreted more sST2 and less TGF-β, which polarized dMΦs toward the M1 phenotype. Moreover, the elevated sST2 biased the efferocytosis-related metabolism of RPL dMΦs toward oxidative phosphorylation and exacerbated the disruption of the IL-33/ST2 signaling pathway. Metabolic disorders also lead to dysfunction of efferocytosis, resulting in more uncleared apoptotic cells and secondary necrosis. We also screened the efferocytotic molecule AXL regulated by IL-33/ST2. This positive feedback axis of IL-33/ST2-AXL-efferocytosis led to pregnancy failure. IL-33 knockout mice demonstrated poor pregnancy outcomes, and exogenous supplementation with mouse IL-33 reduced the embryo losses. These findings highlight a new etiological mechanism whereby dMΦs leverage immunometabolism for homeostasis of the microenvironment at the maternal-fetal interface.

Previous studies concerning the circulating interleukin-17 (IL-17) in systemic lupus erythematosus (SLE) were contradictory.To further precisely investigate circulating IL-17 in SLE and evaluate its influential factors by meta-analysis.EMBASE, PubMed and Cochrane Library were comprehensively searched to obtain studies on circulating IL-17 in SLE patients by November 22, 2018. The results were illustrated by pooled standard mean difference (SMD) with corresponding 95% confidence interval (CI) using random-effects model as there was significant heterogeneity, which was estimated using CochranOverall, 1872 articles were reviewed and 20 studies involving 1067 subjects with SLE and 721 healthy controls (HCs) were enrolled in the final analysis according to inclusion criteria. Compared with HCs, circulating IL-17 levels in SLE patients were elevated (SMD: 1.183, 95% CI: 0.763-1.603;SLE patients have higher circulating IL-17 levels, which is influenced by ethnic, age and disease duration, literature quality and measurements.

Introduction: Autoimmune diseases (ADs) are idiopathic and heterogeneous disorders with contentious pathophysiology. Great strides have been made in epigenetics and its involvement in ADs. Zeste homolog 2 (EZH2) has sparked extensive interest because of its pleiotropic roles in distinct pathologic contexts.Areas covered: This review summarizes the epigenetic functions and the biological significance of EZH2 in the etiology of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), inflammatory bowel disease (IBD), multiple sclerosis (MS), and systemic sclerosis (SSc). A brief recapitulation of the therapeutic potential of EZH2 targeting is provided.Expert opinion: There are questions marks and controversies surrounding the feasibility and safety of EZH2 targeting; it is recommended in RA and SLE, but queried in T1D, IBD, MS, and SSc. Future work should focus on contrast studies, systematic analyses and preclinical studies with optimizing methodologies. Selective research studies conducted in a stage-dependent manner are necessary because of the relapsing-remitting clinical paradigms.

BACKGROUND To assess the non-adherence rate among pulmonary tuberculosis (TB) patients in Anhui Province, eastern China and to explore the influential factors, so as to identify targets for intervention. MATERIAL AND METHODS A total of 339 TB patients were recruited from TB dispensaries in 8 counties of Anhui Province, eastern China using a stratified sampling method. All study subjects were surveyed using a structured questionnaire. Differences between groups involving categorical data were analyzed using the chi-square test. RESULTS Overall, of the 339 patients, 33.63% missed medication. Divorced and widowed patients were more likely to miss medication compared with those who were married or unmarried (P0.01). Regarding the knowledge related to topics such as transmission route, preventive measures, and suspicious symptoms, the awareness rate in the group with good medication compliance was higher than in the group with poor compliance (P0.05). We found that compliance was not significantly associated with seeking medical treatment in professional institutions, the national free TB treatment policy, or discrimination (P0.05). The rate of non-compliance under supervision (26.10%) was lower than that without supervision (64.18%) (P0.001). CONCLUSIONS The anti-TB treatment non-adherence rate in TB patients is relatively high in Anhui Province, eastern China, and is associated with marital status, annual income, TB knowledge, and medical staff visits.

Appropriate decidualization is of great importance for embryo implantation, placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activation of progesterone-mediated signaling pathway, the exact mechanisms have not been elucidated. Here, we demonstrated that both IL-27 and IL27RA were highly expressed in decidua than those in endometrium during secretory phase. Estrogen plus progesterone significantly upregulated the expression of IL-27 and IL-27RA in endometrium stromal cells (ESCs). In addition, inhibiting IL-27 signaling with IL-27 neutralization antibody (anti-IL-27) suppressed the expression of decidualization-related molecules, receptors of estrogen (gene coded by ESR) and progesterone (PGR) induced by cAMP or estrogen plus progesterone. Similar results were obtained from Il27ra

The survival and development of a semi-allogeneic fetus during pregnancy require the involvement of decidual stromal cells (DSCs), a series of cytokines and immune cells. Insulin-like growth factor 1 (IGF1) is a low molecular weight peptide hormone with similar metabolic activity and structural characteristics of proinsulin, which exerts its biological effects by binding with its receptor. Emerging evidence has shown that IGF1 is expressed at the maternal–fetal interface, but its special role in establishment and maintenance of pregnancy is largely unknown. Here, we found that the expression of IGF1 in the decidua was significantly higher than that in the endometrium. Additionally, decidua from women with normal pregnancy had high levels of IGF1 compared with that from women with unexplained recurrent spontaneous miscarriage. Estrogen and progesterone led to the increase of IGF1 in DSCs through upregulating the expression of WISP2. Recombinant IGF1 or DSCs-derived IGF1 increased the survival, reduced the apoptosis of DSCs, and downregulated the cytotoxicity of decidual NK cells (dNK) through interaction with IGF1R. These data suggest that estrogen and progesterone stimulate the growth of DSCs and impair the cytotoxicity of dNK possibly by the WISP2/IGF1 signaling pathway.

Problem Endometrial hyperplasia (EH) is characterized by an endometrial gland-to-stroma ratio >1 and is one of the most common gynecological diseases in the world. The role of immunocyte subsets in the development of EH remains unknown. Methods Patients who underwent dilatation and curettage due to abnormal uterine bleeding were recruited in the present study. Alterations in the numbers of different types of immune cell subsets in the endometrium of patients were analyzed by flow cytometry. Results The present study included 48 patients who were divided into three groups, based on the pathological results: (a) proliferative period (PP, n = 12); (b) simple EH (SEH, n = 30); and (c) complex EH (CEH, n = 6). The results showed that immune cell subpopulations were significantly different between these three groups. Compared with the PP group, the proportion of CD45+ cells and neutrophils and the subtypes of T cells and macrophages were significantly increased in the SEH patients. Compared with the PP and SEH groups, subsets of immunocytes in the CEH group were significantly decreased, including the population of CD45+ cells and the subtypes of T cells and natural killer cells; in contrast, the proportion of macrophages was significantly increased. There were no significant differences between the other cell subsets in each group. Conclusion The changes in immune cell subsets may be closely associated with the progression of EH. Although the specific role of different immune cell subsets in the development of the diseases requires further study, the changes in the proportions of immune cell subsets should not be ignored.

The survival and development of a semi-allogeneic fetus during pregnancy require the involvement of a series of cytokines and immune cells. Chemokines are a type of special cytokine those were originally described as having a role in leukocyte trafficking. CXC chemokine ligand (CXCL) 16 is a member of the chemokine family, and CXC chemokine receptor (CXCR) 6 is its sole receptor. Emerging evidence has shown that CXCL16/CXCR6 is expressed at the maternal-fetal interface, by cell types that include trophoblast cells, decidual stroma cells, and decidual immune cells (eg, monocytes, γδT cells, and natural killer T (NKT) cells). The regulation of expression of CXCL16 is quite complex, and this process involves a multitude of factors. CXCL16 exerts a critical role in the establishment of a successful pregnancy through a series of molecular interactions at the maternal-fetal interface. However, an abnormal expression of CXCL16 is associated with certain pathological states associated with pregnancy, including recurrent miscarriage, pre-eclampsia, and gestational diabetes mellitus (GDM). In the present review, the expression and pleiotropic roles of CXCL16 under conditions of physiological and pathological pregnancy are systematically discussed.

NLRP3, a member of nucleotide-binding domain-(NOD) like receptor family, can be found in large varieties of immune and non-immune cells. Upon activation, the NLRP3, apoptosis-associated speck-like protein (ASC) and pro-caspase-1 would assemble into a multimeric protein, called the NLRP3 inflammasome. Then the inflammasome promotes inflammation (through specific cleavage and production of bioactive IL-1β and IL-18) and pyroptotic cell death. Previous studies have indicated the importance of NLRP3 in regulating innate immunity. Recently, numerous studies have revealed their significance in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc) and inflammatory bowel disease (IBD). In this review, we will briefly discuss the biological features of NLRP3 and summarize the recent progression of the involvement of NLRP3 in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential.

At present, edible marine shellfishes are often contaminated by a combination of different kinds of marine lipophilic toxins. In this study, several common lipophilic shellfish toxins (LSTs) in marine shellfishes were simultaneously detected by liquid chromatography-tandem mass spectrometry, and the safety risk of commercial marine shellfishes was evaluated based on the materiome of LSTs. Under the optimal conditions, the developed method displayed satisfactory recovery values (63.2%–88.8%), precision (relative standard deviations ≤ 14.5%), and sensitivity (limit of detection in the range of 0.54–2.69 ng g−1) for all analytes. Among the 105 commercially available shellfish samples, 42.86% of the samples had at least one kind of toxins. The highest average content was 47.60 μg kg−1 of DTX1, which was the most serious contaminant in marine shellfish samples. Total Exposure Risk Index (∑ERI) was calculated based on Total Daily Intake (TDI) and Acute Reference Dose (ARfD) of each toxin to evaluate the safety risk of commercial marine shellfishes. The results indicated that the risk of toxin poisoning was 19.05% in the commercial available marine shellfishes, and the scallops (Chlamys farreri) have the highest poisoning risk among different shellfishes used in this study. In summary, a new method based on the combined contamination of LSTs was successfully developed for the risk assessment of commercial marine shellfishes. The proposed method is stricter than that in the relevant rules of European Food Safety Authority (EFSA) and can benefit to protect shellfish consumers from poisoning risk.

Objective This study aims at investigating the global public interest in seeking information about systemic lupus erythematosus (SLE) using Google Trends (GT). Methods An electronic search was performed using GT with the search term lupus as well as the option of disease from January 2004 to December 2018. Cosinor analysis was applied to detect the seasonality of SLE-related relative search volume (RSV). In addition, analysis on SLE-related topics including “hot topics” and “top rising topics” was also conducted. Results Overall, SLE-related RSV showed a decreasing trend from January 2004 to December 2013 and then demonstrated a slowly increasing trend from January 2014 to December 2018. Cosinor test showed no significant seasonal variation in SLE-related RSV ( p > .025). RSV peaked in May and reached the trough in November. The top seven rising topics were Selena Gomez, Sjögren syndrome, autoimmunity, rheumatoid arthritis, rheumatology, antinuclear antibody and autoimmune disease. Conclusion The results from GT analysis showed slowly increasing internet searches for SLE in recent years. This trend was followed by a peak of RSV in May and reached its lowest level in November. However, globally, the results did not reveal a significant seasonal variation in GT for SLE. Additionally, the top fast-growing topics regarding SLE may be valuable for doctors and nurses to provide timely education of the disease to patients, as well as promote the development of public health.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by self-perpetuating inflammation and tissue/organ damage, resulting from the failure of lymphocyte auto-tolerance, cause morbidity and mortality worldwide. The current drugs or therapies including conventional non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), as well as several biologic therapies such as B cell-targeted, T cell-targeted, cytokines-targeted and cytokines receptors-targeted therapy, cannot completely cure SLE and RA, and are always accompanied by unexpected side effects. Therefore, more studies have explored new methods for therapy and found that the herbal medicine as well as its natural products (NPs) exhibited promising therapeutic value through exerting effects of immunomodulation, anti-inflammation, anti-oxidation, and anti-apoptosis, etc. via regulating abnormal responses in kidney, innate and adaptive immune systems, intestine, synoviocytes, as well as bone system including chondrocytes, osteoclasts, joints and paw tissues. In the present review, we will elucidate the current mainstream drugs and therapies for SLE and RA, and summarize the efficacy and mechanisms of NPs in the treatment of SLE and RA based on available findings including in vitro and in vivo animal models, as well as clinical studies, and further analyze the existing challenges, in order to provide comprehensive evidence for improvement of SLE and RA therapy by NPs and to promote management of these two autoimmune diseases.

The role of microorganism in human diseases cannot be ignored. These microorganisms have evolved together with humans and worked together with body's mechanism to maintain immune and metabolic function. Emerging evidence shows that gut microbe and their metabolites open up new doors for the study of human response mechanism. The complexity and interdependence of these microbe-metabolite-host interactions are rapidly being elucidated. There are various changes of microbial levels in models or in patients of various autoimmune diseases (AIDs). In addition, the relevant metabolites involved in mechanism mainly include short-chain fatty acids (SCFAs), bile acids (BAs), and polysaccharide A (PSA). Meanwhile, the interaction between microbes and host genes is also a factor that must be considered. It has been demonstrated that human microbes are involved in the development of a variety of AIDs, including organ-specific AIDs and systemic AIDs. At the same time, microbes or related products can be used to remodel body's response to alleviate or cure diseases. This review summarizes the latest research of microbes and their related metabolites in AIDs. More importantly, it highlights novel and potential therapeutics, including fecal microbial transplantation, probiotics, prebiotics, and synbiotics. Nonetheless, exact mechanisms still remain elusive, and future research will focus on finding a specific strain that can act as a biomarker of an autoimmune disease.

Extracellular toxins released by marine toxigenic algae into the marine environment have attracted increasing attention in recent years. In this study, profiling, characterization and quantification of extracellular toxin compounds associated with diarrhetic shellfish poison (DSP) in the culture medium of toxin-producing dinoflagellates were performed using high-performance liquid chromatography–high-resolution mass spectrometry/tandem mass spectrometry for the first time. Results showed that solid-phase extraction can effectively enrich and clean the DSP compounds in the culture medium of Prorocentrum lima (P. lima), and the proposed method achieved satisfactory recoveries (94.80%–100.58%) and repeatability (relative standard deviation ≤9.27%). Commercial software associated with the accurate mass information of known DSP toxins and their derivatives was used to screen and identify DSP compounds. Nine extracellular DSP compounds were identified, of which seven toxins (including OA-D7b, OA-D9b, OA-D10a/b, and so on) were found in the culture medium of P. lima for the first time. The results of quantitative analysis showed that the contents of extracellular DSP compounds in P. lima culture medium were relatively high, and the types and contents of intracellular and extracellular toxins apparently varied in the different growth stages of P. lima. The concentrations of extracellular okadaic acid and dinophysistoxin-1 were within 19.9–34.0 and 15.2–27.9 μg/L, respectively. The total concentration of the DSP compounds was within the range of 57.70–79.63 μg/L. The results showed that the proposed method is an effective tool for profiling the extracellular DSP compounds in the culture medium of marine toxigenic algae.

With the change of business environment for Chinese private companies, performance evaluation system based on EVA and BSC has been introduced into performance evaluation for these companies. This paper describes the status quo of performance evaluation system in Chinese private companies firstly, then discusses the design of performance evaluation system based on EVA and BSC, and finally analyzes the process of applying the system and applying requirements.