Chinese and Western medicine treatment of blocking antibody in recurrent spontaneous abortion

The causes of recurrent spontaneous abortion are complex traditional Chinese medicine holds that its etiology is losses of spleen and kidney qi, qi and xue deficiency, in addition to secretion, genetic, anatomical, infection, systemic diseases, environmental factors and other related immune factors, the deficiency of blocking antibody is also one of the reasons for the lack of immune factors. In treating it, Chinese medicine treatment combines the patients personal constitution and treatment based on syndrome differentiation; Western medicine treatment mainly applies Aspirin, active immune lymphocyte treatment, low molecular heparin, gamma globulin protein passive immune treatment and psychological intervention therapy. In this paper, a review of the treatment methods for closed antibodies in the past 5 years is made.

Effect of CD86 blockage on the expressions of TGF-β1,MMP-9,TIMP-3 and PAI-1 proteins and outcome of pregnancy in murine abortion-prone model

In the present study, the effect of blockage of the costimulatory signal CD86 at time of implantation on the expressions of TGF-β1, MMP-9, TIMP-3 and PAI-1 proteins at the maternal-fetal interface and the outcome of pregnancy in mufine abortion-prone model was investigated, in which the CBA/J × DBA/2 matings were used as the abortion-prone model and the CBA/J × BALB/c matings used as the normal pregnant model. The study was performed in following three groups： 2 groups of the abortion-prone model, which were experimental group and control experimental group, and 1 group of normal pregnant model, and each group had 10 pregnant CBA/J mice exclusively. Female pregnant CBA/J mice in the experimental group received an intraperitoneal （i. p. ） injection of 100μg of antimouse CD86 mAb in 200 μl of PBS at day 4.5 of gestation, and the irrelevant-isotope matched rat IgG2b was administrated in the control experimental group with the same dosage and at same time. For the normal pregnant group, no treatment was given. The pregnant CBA/J mice were killed on day 13.5 of gestation. Then, the embryo resorption rate was calculated and the expressions of TGF-β1, MMP-9, TIMP3 and PAI-1 were detected by using immunohistochemical methods. It was demonstrated that the embryo resorption rate in the experimental group was significantly reduced in comparison with that in the control experimental group （X^2 = 7.441, P = 0.006）, but there was no significant difference with that in normal pregnant group （X^2 = 0.016, P = 0.898）. The expressions of TGF-β1 and PAI-1 in the experimental group were significantly increased in comparison with that in the control experimental group （P =0.010, P = 0.003, respectively）, with no significant difference from that in the nonnal pregnant group （P = 0.500）. However, the expression of MMP-9 in the experimental group was significantly reduced in comparison with that in the control experimental group （P = 0.012） with no significant difference from that in the normal pregnant group （P = 0.500）. The expression of TIMP-3 in the experimental group showed no significant difference both with the control experimental group （ P = 0. 328） and the normal pregnant group （ P = 0. 500）. It is concluded that the blockage of the costimulatory molecule CD86 at early stage of gestation can render TGF-β1, MMP-9, TIMP-3 and PAI-1 proteins to express their immuno-tolerant effects through their characteristic pathways and induce the reduction of the embryo resorption rate in the natural abortion-prone model of mice to the level of normal pregnancy.

Animal study on CD4^(+) CD25^(+) regulatory T cells for treating female mouse with recurrent spontaneous abortion

Objective:To explore immunotherapy effectiveness of the CD4^(+)CD25^(+) regulatory T cells for treating female mouse with recurrent spontaneous abortion(RSA)by animal experiments.Methods:Mononuclear lymphocytes were isolated from the blood(instead of cord blood)of new-born baby of KunMing Bai mouse or BALB/c male mouse with normal birth ability(as unrelated third party blood source)by density gradient centrifuga-tion method.The CD4^(+)CD25^(+) regulatory T cells were selected by magnetic-activated cell sorting from mononuclear cells of cord blood cells.CBA/J female mouse copulated with DBA/2J male mouse was utilized as RSA animal model.Pregnant RSA mice were injected different types of lymphocytes through tail vein.Independent sample t-test was used to analyze the data from each group.Results:The proportion of CD4^(+)CD25^(+)T cells in CD4^(+)T cells was(17.49±0.60)%in CD4^(+)CD25^(+) regulatory T cells injection group,which was statistical significant higher than that of mononuclear lymphocyte injection group(14.68±0.83)%,sterile PBS group(9.54±0.85)%or no injection group(9.28±0.68)%(p<.05,t-value was 4.754,13.242 and 15.621,respec-tively).The Foxp3 relative protein expression level of CD4^(+)CD25^(+) regulatory T cells injected group was 5.85±0.45,which was also significant higher than that of mononuclear lymphocyte injection(2.86±0.54),sterile PBS group(1.08±0.16)or no injection group(1.00±0.00)(p<.05,t-value was 7.276,17.227 and 18.635,respectively).Finally,two times of CD4^(+)CD25^(+)T cell injected group at the 4 th and 8 th day had well effect for RSA mouse,and embryo sorption rate was(4.92±0.08)%,which significant lower than that of two times of mononuclear lymphocyte injected group(13.07±0.06)%,sterile PBS group(23.11±0.12)%,or no injection group(25.47±0.11)%(p<.05,t-value was-2.603,-4.012 and-4.700,respectively).Conclusions:Pregnant mouse with RSA injected CD4^(+)CD25^(+)T cells several times for immunotherapy can get better effec-tiveness than that of pregnant mouse injected traditional mononuclear cells.

Treatment of Integrated Traditional and Western Medicine in Recurrent Spontaneous Abortion of Immune Abnormality Type

Objective: Immune abnormality type of recurrent spontaneous abortion (RSA) is an important etiological type, major findings of that are the abnormal increases in auto and/or allo-antibodies of anti-zona pellucida, anti-phospholipid and anti-ABO blood group. The purpose of the present study is to assess the clinical values of integrated traditional and western medicine in treating the immune abnormality type of RSA.Methods: The aborters were treated by Zhibai Dihuang Pills for anti-zona pellucida antibodies, and clearing evil Heat, removing Dampness, replenishing blood and activating circulation by Chinese medicinal herbs recipe for anti-phospholipid and anti-ABO group antibodies.Results: After they had been treated by these recipes, 92.3% became pregnant with normal delivery. It was found in dynamic investigation that level of the antibodies turned to decrease gradually during the treatment, and that of anti-phospholipid and anti-ABO group antibodies increased again at beginning of pregnancy and then decreased gradually with continuing the treatment.Conclusion: Chinese herbs recipe could be used to treat RSA of immune abnormality-type by way of decreasing the elevated levels of auto and/or allo-antibodies.

Efficacy and safety of Tripterygium wilfordii glycosides tablets combined with Western medicine for patients with rheumatic immune diseases

BACKGROUND Rheumatic immune diseases are a group of chronic inflammatory diseases charac-terized by joint and systemic multi-organ involvement,including rheumatoid arthritis,systemic lupus erythematosus,and Sjogren’s syndrome,among others.The pathogenesis of these diseases is related to the abnormal activation and regulatory imbalance of the immune system.The prevalence and morbidity of rheumatic immune diseases are high,imposing a significant burden on patients'quality of life and socio-economic costs.Currently,the treatment of rheumatic immune diseases mainly relies on Western medicine,such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,and biologics.However,the therapeutic effects of Western medicine are not ideal,some patients poorly respond or are resistant to Western medicine,and long-term use often causes various adverse reactions.AIM To systematically evaluate the efficacy and safety of Tripterygium wilfordii gly-cosides tablets combined with Western medicine in the treatment of patients with rheumatic immune diseases.METHODS This study conducted a meta-analysis to systematically evaluate the efficacy and safety of Tripterygium wilfordii glycosides tablets combined with Western medicine for patients with rheumatic immune diseases.Chinese and English databases were searched for randomized controlled trials(RCTs)on the treatment of rheumatic immune diseases with Tripterygium wilfordii glycosides tablets combined with Western medicine.The quality of the included studies was assessed using the Cochrane risk of bias assessment tool.Meta-analysis was performed using RevMan 5.4 software.RESULTS The meta-analysis included 11 RCTs involving 1026 patients with rheumatic immune diseases.The combined treatment significantly reduced the risk of disease recurrence(relative risk=1.07,95%confidence interval:1.01-1.15,P<0.05)and showed no significant heterogeneity(I2=0%,P=0.53),indicating that Tripterygium wilfordii glycosides tablets combined with Western medicine is an effective method to reduce the possibility of postoperative recurrence in patients with rheumatic immune diseases.However,due to the limited number and quality of the studies included,these results should be interpreted with caution.CONCLUSION Tripterygium wilfordii glycosides tablets combined with Western medicine is an effective and safe treatment option for patients with rheumatic immune diseases and can be considered a clinical choice.However,more high-quality research is needed to validate this conclusion and provide more solid evidence for clinical practice.

Effect of Yangxue Antai Granule (养血安胎冲剂) in Prevention and Treatment of Abortion and Short Life T-Suppressor Cell

Objective: To study the influence of T suppressor cell activity on habitual abortion (HA) and to observe the regulatory effect of Yangxue Antai Granule (YXATG) on T suppressor cell and its effect on fetus preservation. Methods: T suppressor cell activities of 56 pregnant women with HA history were tested with method of short life T suppressor cell activity (MTT method) during early pregnancy, and were followed up in middle and late pregnancy in 20 cases of them. All the 56 patients received YXATG treatment. Groups of normal early pregnant, normal non pregnant women and those non pregnant but with history of habitual abortion were involved in this study as control. Results: T suppressor cell activity in early pregnancy was lower than that of middle and late pregnancy ( P <0.01, P <0.001) and also lower than that of the control groups ( P <0.01, P <0.001). The successful rate of fetus preservation of YXATG was 98.2%, and 98.0% of the cases got normal delivery. Conclusion: Low T suppressor cell activity might be the immunologic etiology of HA. The fetus preservative effect of YXATG might be due to its regulatory effect on T suppressor cell activity.

Effect of Traditional Chinese Medicine Treatment on Levels of Blocking Antibody, β-hCG, Progesterone and Estradiol in Spontaneous Abortion

Objective: To explore the effect of traditional Chinese medicine (TCM) on abnormalmaternal-fetal immune and endocrine in 24cases of threatened abortion (TA) and 68 cases of recurrent spontaneous abortion (RSA).Methods: The levels of blocking effect (BE),antiidiotype antibody (AIA), cytotoxin antibody (CTA), β-human chorionic gonadotropin(β-hCG), progesterone (P), estradiol (E2)were measured in all 92 patients. Results: Incidence rates of the lack of BE, AIA and CTAin 92 cases were 60. 87%, 57. 61 % and 72.83% respectively. The lower levels of BE,AIA and CTA were elevated significantly (P< 0. 05 ～0. 01 ), and the serial levels β- hCG, P and E2 were markedly increasing (P< 0. 01 ) in all successful pregnant patients.The rate of the successful pregnancy of 92 cases was 89. 13 % (to TA 91. 67%, to RSA 88.24 % respectively). Conclusions: It suggeststhat the lack of blocking antibody (BA) andendocrine hormone deficiency may result inspontaneous abortion during early pregnancy.The therapeutic mechanism of those herbs intreating spontaneous abortion was associatedwith the growing levels of BA and hormone byregulating the maternal-fetal immunity and endocrine.

New Progress regarding the Use of Lactic Acid Bacteria as Live Delivery Vectors, Treatment of Diseases and Induction of Immune Responses in Different Host Species Focusing on <i>Lactobacillus</i>Species

Lactobacillus species are non-spore-forming, gram-positive bacteria and lactic acid producing bacteria (LAPB) that naturally inhabit the human and animal gastrointestinal and mouth organs. The aim of this review was to evaluate the new progress regarding the use of Lactobacillus species as live delivery vectors, prevention, and treatment of pathogenic and metabolic diseases. Lactobacillus strains of probiotics have been extensively studied and have confirmed that they can absolutely improve performance as live delivery vectors, a treatment option of various diseases such as: Hemorrhagic cecal coccidiosis in young poultry, hypertension, avian flu, obesity, diabetes, Derzsy’s disease or parvovirus infection, human immunodeficiency virus infections, irritable bowel syndrome, gastrointestinal disorders, Fungal infections, vaginal eubiosis, fish and shellfish species diseases. We give you an idea about that Lactobacillus species have been proficient in preventing and treating both disorders in animal models and some are used for clinical trials. We present the most current studies on the use of Lactobacillus strains that had an impact on an effective immune response to a specific antigen because a variety of antigens have been expressed. Therefore Lactobacillus strains can be considered as good candidates because of its potential for diseases treatment and vaccine development as heterologous protein secretion to date.

Atopic eczema treatment now and in the future:Targeting the skin barrier and key immune mechanisms in human skin

The skin facilitates a number of key roles but its functioning can be impaired by disease. Atopic eczema is a chronic inflammatory disease where the skin barrier has become leaky, and inflammation occurs. It affects up to 20% of children and 3% of adults worldwide, manifesting as red itchy patches of skin with varying severity. This review aims to investigate the leaky skin barrier and immune mechanisms from the perspective of potential novel treatments. The complexity of atopic eczema as a disease is what makes it difficult to treat. Genome-wide association studies have highlighted possible genetic variations associated with atopic eczema, however in some cases, individuals develop the disease without these genetic risk factors. Loss of function mutations in the filaggrin gene are one of these associations and this is plausible due to its key role in barrier function. The Th2 immune response is the link with regards to the immune mechanisms as atopic inflammation often occurs through increased levels of interleukin(IL)-4 and IL-13. Eczematous inflammation also creates susceptibility to colonisation and damage by bacteria such as Staphylococcus aureus. Potential novel treatments are becoming ever more specific, offering the hope of fewer side effects and better disease control. The best new treatments highlighted in this review target the immune response with human beta defensin 2, phosphodiesterase-4 inhibitors and monoclonal antibodies all showing promise.

Gut microbiota and immune system in liver cancer:Promising therapeutic implication from development to treatment

Liver cancer is a leading cause of death worldwide,and hepatocellular carcinoma(HCC)is the most frequent primary liver tumour,followed by cholangiocarcinoma.Notably,secondary tumours represent up to 90% of liver tumours.Chronic liver disease is a recognised risk factor for liver cancer development.Up to 90% of the patients with HCC and about 20% of those with cholangiocarcinoma have an underlying liver alteration.The gut microbiota-liver axis represents the bidirectional relationship between gut microbiota,its metabolites and the liver through the portal flow.The interplay between the immune system and gut microbiota is also well-known.Although primarily resulting from experiments in animal models and on HCC,growing evidence suggests a causal role for the gut microbiota in the development and progression of chronic liver pathologies and liver tumours.Despite the curative intent of“traditional”treatments,tumour recurrence remains high.Therefore,microbiota modulation is an appealing therapeutic target for liver cancer prevention and treatment.Furthermore,microbiota could represent a non-invasive biomarker for early liver cancer diagnosis.This review summarises the potential role of the microbiota and immune system in primary and secondary liver cancer development,focusing on the potential therapeutic implications.

Redox, immune and genetic biomarker system for personalized treatments in colorectal cancer

BACKGROUND Identifying biomarkers for the risk of developing degenerative processes linked to aging and colorectal cancer(CRC) onset that could improve clinical strategies.AIM To determine valid targets and a predictive biomarker's system of chronicization of inflammation for cancer treatment.METHODS A group of 147 CRC patients was studied. Clinical diagnosis was confirmed histopathologically, and patients were sub-typed using the pathological tumornode-metastasis classification. Thirteen colon adenoma patients and 219 healthy subjects were also studied. A system biology study on Thioredoxin1/CD30 redox-immune systems(Trx1/CD30), T helper cytokines and polymorphisms of killer immunoglobulin-like receptors, FcγRIIa-131 H/R and FcγRIIIa-158 V/F was carried out. Enzyme-linked immunosorbent assay was performed to analyze sera.Genetic study was executed by polymerase chain reaction sequence-specific primers and sequence-based typing method. Statistical analysis was performed by using the "Statgraphics software systems".RESULTS We found a positive increase between Trx1/RTrx1 levels and sCD30 level and increased age. With respect to the gender relationships, there were distinct differences. Females showed a primary relationship between transforming growth factor beta(TGFβ) with Trx1, whereas males had one with TGFβ and RTrx1. Trx1/CD30 controls the redox immune homeostasis, and an imbalance in the relationship between the Trx1/RTrx1 and sCD30 levels is linked to the onset and progression of tumor. This event happens through different gender-specific cytokine pathways. Our study demonstrated that the serum levels ofTrx1/RTrx1, TGFβ/interleukin(IL)6 and TGFβ/IL4 combinations and the sCD30,IFNγ and IL2 combination constitute a predictive gender specific biomarker system. This is relevant for clinical screening to detect the risk of the potential development or progression of a tumor.CONCLUSION Oxidative stress on Trx1/CD30 is a trigger of cancer disease, and the selected oxidation and immune products are a biomarker system for aging and cancer.

IN VITRO ANTI-HEPATOMA EFFECTS OF MONOCYTES AND KUPFFER CELLS ISOLATED FROM HEPATOMA PATIENTS AFTER TREATMENT WITH BIOLOGICAL IMMUNE STIMULANTS

Monocytes (MC), lymphocytes (LC) and Kupffer cells (KC) were isolated respectively from blood and surgical liver samples of patients suffering from he-patocellular carcinoma (HCC). 13 patients were given BCG, mixed bacterium vaccine (MBV) and human white blood cell interferon (IFN), the other 3 patients were not treated with any biological immune stimulants (BIS) and served as controls. The cytosta-tic and cytotoxic effects of MC and KC on human hepatoma SMMC-7721 (TC) were assayed in vitro and the numbers of T total (Tt), T helper (Th) and T suppressor (Ts) cells were counted using CD monoclonal antibody immunofluorescence. The results were as follows: (1) On the 7th day after the first administration of BIS, the cytostatic and cytotoxic effects of MC on TC showed obvious increase over pre-administration. The activity of BIS was 1 ?5 times as high as that in the controls. (2) After 3 administrations, the cytostatic effect of MC on TC increased to the normal level (84%), while the controls remained as before (45%). (3) On the 7th day after first administration, cytostatic and cytotoxic effects of KC on TC were 0.5 and 1 times higher respectively than those of the controls. (4) The numbers of Tt and Th of patients given BIS increased continuously; on the contrary Ts decreased in number. These results indicate that combined use of BCG, MBV and IFN can actively enhance the immune anti-hepatoma function of patients suffering from HCC.

Application of Clinical Nursing Pathway Combined with Cluster Nursing Mode in Biologic Treatment of Rheumatoid Immune Disease Patients

Objective: To investigate the effect of clinical nursing pathway (CNP) combined with cluster nursing mode in intravenous biologic treatment of rheumatoid immune disease patients. Methods: Convenience sampling method was used to select inpatients receiving biologics treatment in Rheumatology and Immunology Department of a grade A hospital in Jingzhou city from May 2020 to April 2022. 75 patients from May 2020 to April 2021 were selected as the control group, and 75 patients from May 2021 to April 2022 were selected as the observation group. The control group was given routine care. The observation group was treated with CNP combined with cluster nursing mode on the basis of the control group, and the incidences of adverse infusion reactions, total treatment time, patient satisfaction and nurse satisfaction were compared between the two groups. Results: There were statistically significant differences between the two groups after intervention (P Conclusion: Using CNP combined with cluster nursing mode is beneficial to reduce the incidence of adverse infusion reactions in patients, shorten the total treatment time, and improve the satisfaction of patients and nurses.

Correlation Between Granulomatous Mastitis and Autoimmune Function and the Immuneregulating Role of Traditional Chinese Medicine

Granulomatous mastitis(GM)is a benign granulomatous condition,and its pathogenesis may be related to autoimmune disorders.Cellular immunity,humoral immunity,immunoglobulins,and complement could all play a role in the disease process,showing certain clinical patterns.Corticosteroids can quickly control disease progression,and immunosuppressants can be used for complex and refractory GM cases.In traditional Chinese medicine(TCM),“healthy qi”is similar to immune system function.For GM with deficient healthy qi,TCM treatments such as internal and external herbal applications can help regulate immune function and shorten disease duration by staged and TCM treatment,regulating viscera,reinforcing healthy qi,and eliminating pathogenic factors.

Tumor-infiltrating T-Lymphocyte immunity-related immune tolerance and anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy for advanced hepatocellular carcinoma

Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.

Application of Clinical Nursing Pathway in the Peri-Treatment Period of Immunoadsorption Therapy for Rheumatic Immune Diseases

Objective: The paper aims to investigate the clinical nursing pathway (CNP) in the application of immunosorption therapy in patients with rheumatic immune disease. Methods: Convenience sampling method was used to select inpatients who received immunoadsorption therapy from January 2020 to December 2022 in the rheumatology and Immunology department of a 3A hospital in Jingzhou City. 30 patients from January 2020 to June 2021 were selected as control group, and 30 patients from July 2021 to December 2022 were selected as observation group. The control group was given routine nursing. On the basis of the control group, the observation group used a clinical nursing pathway for intervention during the perioperative period of immunosorbent therapy. The incidence of adverse reactions, patient satisfaction, and nurse satisfaction during immunosorbent therapy between the control group and the observation group were compared. Results: After intervention, the incidence of adverse reactions in the observation group was significantly lower than that in the control group, while patient satisfaction and nurse satisfaction in the observation group were significantly higher than those in the control group. The results are all statistically significant (P Conclusion: Clinical nursing pathway is beneficial to reduce the incidence of adverse reactions in patients with immunoadsorption during peri-treatment and improve the satisfaction of patients and nurses.

不同细胞来源外泌体miRNAs在胃癌进展及诊断和预后中的作用

背景:肿瘤微环境可通过多种途径参与胃癌的发生发展并促进胃癌化疗耐药,其中外泌体miRNAs介导的肿瘤微环境串话可诱导基质重编程,参与肿瘤异质性,并形成有利于肿瘤增殖、迁移、侵袭、免疫逃逸和化疗耐药的微环境。目的:对近年来外泌体miRNAs在胃癌微环境中的作用机制及其在胃癌诊断及预后评估中的应用进展作一综述。方法:以“Exosomal miRNAs,gastric cancer,angiogenesis,apoptosis,proliferation,migration,autophagy,invasion,immune response,chemotherapy resistance,biomarker”为英文检索词和“外泌体miRNAs,胃癌”为中文检索词分别检索PubMed及中国知网数据库。检索时限为2017-2024年。通过阅读文题及摘要进行初步筛选,排除研究内容相关性差及内容重复的文献,最终纳入77篇文献进行归纳探讨。结果与结论:①外泌体作为细胞间信息交流的重要载体,可携带miRNA等多种信息物质,通过激活靶细胞上的细胞表面受体、与受体细胞质膜融合及内吞作用3种途径实现细胞间信号传递。②外泌体miRNAs通过调节胃癌细胞增殖、凋亡、自噬、血管形成、侵袭转移、免疫应答以及耐药性的形成等多种途径,进而在胃癌进展中发挥着重要作用。③miRNA与靶mRNA相互作用及其调控网络广泛存在于肿瘤发生和人类癌症发展中,不同类型外泌体miRNAs对调控胃癌细胞凋亡具有不同的作用,鉴别不同外泌体miRNAs对胃癌细胞凋亡相关蛋白及通路的影响,合理运用其诱导剂或抑制剂可对胃癌细胞凋亡水平进行调控。④不同细胞来源的外泌体miRNAs通过将M1极化型巨噬细胞诱导为M2型,在肿瘤微环境的建立、血管生成、免疫应答及化疗耐药中扮演重要角色。⑤外泌体miRNAs广泛稳定存在于血液及其他体液中,其在胃癌患者中的差异性表达可作为胃癌患者诊断、预后及治疗依据。目前作为生物标志物研究较多的外泌体miRNAs包括miR-379-5p,miR-590-5p,miR-29s和miR-21等,其中miR-590-5p灵敏度与特异性分别为63.7%和86%,其表达水平与胃癌患者总体生存率、浸润深度密切相关。⑥设计外泌体miRNAs模拟物或抑制物,并利用纳米递送载体(如外泌体、脂质体)将其靶向递送至肿瘤部位以恢复miRNAs正常水平,可能是治疗胃癌的一种新策略。⑦虽然外泌体miRNAs在胃癌患者诊疗中具有很大的应用前景,但仍存在一些问题亟待解决,例如外泌体miRNAs的潜在靶点及作用机制尚未完全探讨,其有效性及安全性有待进一步确认;而且外泌体的提取及纯化缺乏标准化规模化制备流程等。

Effect of blockage of costimulatory signal on murine abortion-prone model

Background Inhibition of the key costimulatory signals results in T cell anergy, indicating the alloantigen-specific immunologic unresponsiveness. In this study, the effect of blockage of costimulatory signal CD86 on murine abortion-prone model was studied. Methods Thirty CBA/J female mice cohabitated with DBA/2 male or BALB/c male mice were investigated. CBNJ xDBN2 matings were used as the abortion-prone model, and CBA/J × BALB/c matings were used as the normal pregnant model. The abortion-prone models were divided into experimental and control groups, and the normal pregnant models were set as a normal group （10 mice in each group）. The mice in the experimental group were treated with anti-mouse CD86 monoclonal antibody （mAb） （100 μg） on day 4.5 of gestation, while the controls received irrelevant-isotype matched rat IgG2b. As for the normal group, nothing was given to the mice. The mice were killed on day 13.5 of gestation, embryo resorption rate and the expression of transforming growth factor β1 （TGF-β1）, plasminogen activator inhibitor 1 （PAI-1）, and matrix metalloproteinase 9 （MMP-9） were detected. Then the data were analyzed by Chi-square test and Fisher＇s exact test. Results The embryo resorption rate in the experimental （8.2%） and normal groups （7.7%） was significantly lower than that of the control （23.5%, P〈0.05）. No significant difference was detected between the experimental and normal groups （P〉0.05）. The positive expression rates of TGF-β1 and PAl-1 proteins in the experimental and normal groups were significantly higher than those in the control group （P〈0.05）. The positive expression rate of MMP-9 protein in the experimental and normal groups was significantly lower than that in the control group （P〈0.05）. No significant difference in the positive expression rates of the three proteins was detected between the experimental and normal groups （P〉0.05）. Conclusions Blockage of costimulatory signal CD86 at early pregnancy can treat uncertain recurrent spontaneous abortion by stimulating the expression of TGF-β1, MMP-9 and PAl-1 and reducing the embryo resorption rate.

Multiple immune disorders in unrecognized celiac disease:a case report

We reported a female patient with unrecognized celiac disease and multiple extra intestinal manifestations, mainly related to a deranged immune function, including macroamilasemia, macrolipasemia, IgA nephropathy,thyroiditis, and anti-b2-glicoprotein-1 antibodies, that disappeared or improved after the implementation of a gluten-free diet.