Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

Immune remodulation in pediatric inherited metabolic liver diseases

Inherited metabolic liver diseases arise from genetic mutations that lead to dis-ruptions in liver metabolic pathways and are predominantly observed in pedia-tric populations.The spectrum of genetic metabolic liver disorders is diverse,encompassing a range of conditions associated with aberrations in iron,copper,carbohydrate,lipid,protein,and amino acid metabolism.Historically,research in the domain of genetic metabolic liver diseases has predominantly concentrated on hepatic parenchymal cell alterations.Nevertheless,emerging studies suggest that inherited metabolic liver diseases exert significant influences on the immune microenvironment,both within the liver and systemically.This review endeavors to encapsulate the immunological features of genetic metabolic liver diseases,aiming to expand the horizons of researchers in this discipline,and to elucidate the underlying pathophysiological mechanisms pertinent to hereditary metabolic liver diseases and to propose innovative therapeutic approaches.

Microglia lactylation in relation to central nervous system diseases

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

Correlative factors of poor prognosis and abnormal cellular immune function in patients with Alzheimer’s disease

BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important.AIM To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in patients.METHODS A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020.Collect cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other data.Multivariate logistic regression analysis was used to determine independent prog-nostic factors.the modified Rankin scale(mRS)was used to determine whether the prognosis was good.The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.RESULTS Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD patients.Multivariate logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of AD.The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD.It is recommended that the proportion of T lymphocytes<55%is used as the cut-off threshold for predicting the poor prog-nosis of AD.The early and continuous drug treatment is associated with a good prognosis.

Predictors of prognosis in Alzheimer’s disease: The role of cognitive dysfunction, immune abnormalities, and advanced neuroimaging

Alzheimer’s disease(AD)is a grave illness that results in cognitive and social issues.A recent study examined the association between neuroimaging results,cognitive dysfunction,atypical cellular immune function,and poor prognostic factors in AD patients who demonstrated poor prognosis.Poor prognosis was associated with abnormal cellular immune function,extrapyramidal symptoms,altered consciousness,abnormal electroencephalogram,modified Rankin scale,increased neutrophil lymphocyte ratio,and severe pneumonia.The impaired cellular immune function characterized by a reduction in the blood T lym-phocytes’proportion predicted poor prognosis as an independent risk factor in AD.Early initiation and maintenance of AD medications is associated with better outcomes.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Exploring the relationship between gut microbial ecology and inflammatory disease:An insight into health and immune function

The immune system,host brain development,and general metabolism are all influenced by the gut bacteria.Bacteria make up the majority of the gut microbiota in mammals.The mouse has been the most often used animal model in preclinical biological research.In mice,Firmicutes and Clostridiales are prominent.On the other hand,Bacteroidaceae,Prevotellaceae,and Firmicutes are commonly found in humans.In this review,we performed a detailed study by focusing on a comparison between human and murine gut microbiomes,role of the microbiome and their secreted metabolites in regulating gut immunity to maintain homeostasis,and changes in the microbial composition in the dysbiotic state.

Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases

AIM To investigate whether immune mediated diseases(IMD) are more frequent in patients with inflammatory bowel disease(IBD).METHODS In this population based registry study,a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16,2013. Controls were randomly selected from the Danish Civil Registration System(CRS) and matched for sex,age,and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis(UC),Crohn's disease(CD) and Both the latter referring to those registered with both diagnoses. Subsequently,odds-ratios(OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P-values were estimated using Fisher's exact test.RESULTS There were significantly more women than men in the registry,and a greater percentage of comorbidity in the IBD groups(P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased(P < 0.00125) for primary sclerosing cholangitis(PSC),celiac disease,type 1 diabetes(T1D),sarcoidosis,asthma,iridocyclitis,psoriasis,pyoderma gangrenosum,rheumatoid arthritis,and ankylosing spondylitis. Restricted to UC(P < 0.00125) were autoimmune hepatitis,primary biliary cholangitis,Grave's disease,polymyalgia rheumatica,temporal arteritis,and atrophic gastritis. Restricted to CD(P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC(P < 0.00125) were atrophic gastritis,rheumatoid arthritis,temporal arteritis,and polymyalgia rheumatica. Restricted to women with CD were episcleritis,rheumatoid arthritis,and psoriatic arthritis. The only disease restricted to men(P < 0.00125) was sarcoidosis. CONCLUSION Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways.

Neurodegenerative diseases as proteinopathies-driven immune disorders

In the pathophysiology of neurodegenerative disorders,the role of misfolded protein deposition leading to neurodegeneration has been primarily discussed.In the last decade,however,it has been proposed a parallel involvement of innate immune activation,chronic inflammation and adaptive immunity in the neurodegeneration mechanisms triggered by proteinopathies.New insights in the neurodegenerative field strongly suggest a role for the immune system in the pathophysiology of neurodegenerative disorders.Therefore,the hypothesis underlining the modulation of the innate and the adaptive immune system in the events linked to brain deposition of misfolded proteins could open new perspectives in the setting of specific immunotherapeutic strategies for the treatment of neurodegenerative diseases.Therefore,we have reviewed the pathogenic hypothesis in neurodegenerative pathologies,underling the links between the deposition of misfolded protein mechanisms and the immune activation.

STAT3 in immune responses and inflammatory bowel diseases

STAT3 has been known as a mediator for gene expression induced by many important cytokines. Recent studies have suggested that STAT3 has important functions in regulation of both innate and adaptive immunity. Loss of STAT3 in immune cells caused severe inflammation in response to pathogens. This review discusses the recent progress and suggests directions for the future research on this interesting molecule.

B Cells with Regulatory Function in Animal Models of Autoimmune and Non-Autoimmune Diseases

Although the identification of B cell subsets with negative regulatory functions and the definition of their mechanisms of action are recent events, the important negative regulatory roles of B cells in immune responses are now broadly recognized. There is an emerging appreciation for the pivotal role played by B cells in several areas of human diseases including autoimmune diseases and non-autoimmune diseases such as parasite infections and cancer. The recent research advancement of regulatory B cells in human disease coincides with the vastly accelerated pace of research on the bridging of innate and adaptive immune system. Current study and our continued research may provide better understanding of the mechanisms that promote regulatory B10 cell function to counteract exaggerated immune activation in autoimmune as well as non-autoimmune conditions. This review is focused on the current knowledge of BREG functions studied in animal models of autoimmune and non-autoimmune diseases.

Research Progress on the Immunomodulatory Effect of Trace Element Selenium and Its Effect on Immune-Related Diseases

Selenium,one of the essential trace elements in the body,has a variety of biological functions including antioxidant activity,immunity enhancement and anti-tumor effect,and has the potential to be further developed into new drugs.In this paper,the research progress on the immunomodulatory effect of selenium and its mechanism and the effects of immune-related diseases in recent years were reviewed,and its future research and application were prospected.It is hoped to provide reference for further exploring the immune regulation effect and application of selenium.

Fixed-point Monitoring of Vaccine Immune Effects on Severe Animal Diseases in Livestock and Poultry Breeding Fields

In order to reveal the immune antibody levels and immune effect of livestock and poultry in the locality,we performed antibody surveillance on severe animal diseases in 17 livestock and poultry fields in six administrative districts of Wuhan City. The results showed that the vaccines had a good protective efficacy on highly pathogenic avian influenza( HPAI) and Newcastle disease( ND) in Wuhan City. The whole antibody levels kept above the ministerial standard( 】 70%).However,the vaccine immunity of porcine reproductive and respiratory syndrome( PRRS),swine fever( SF) and foot and mouth disease( FMD) was still poorly protective. The data indicated that the vaccines are protecting the severe animal diseases well,but there are still some potential security holes in some administrative districts.

Scientific connotation of “treating different diseases with the same method” from the perspective of metabolic-immune dysregulation in inflammation-mediated carcinogenesis of digestive organs

Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.

Pernicious Anemia Associated Autoimmune Diseases in a Sub Saharian African Internal Medicine Service

Introduction: Pernicious anemia is an autoimmune disease. It is characterized by the presence of an autoimmune atrophic gastritis and various autoantibodies that lead to a vitamin B12 deficiency responsible for a macrocytic anemia. It is frequently associated with other specific or non-organ- specific autoimmune diseases. We report six patients with pernicious anemia associated with other autoimmune diseases. Patients and Results: There were six patients (4 females/2 males), mean age of 39.67 years. In all cases it was found macrocytic anemia. The average Hb was 6.08 g/dl and the average MGV: 110.67 fl. Bone marrow aspiration was performed in all patients. Megaloblastosis compatible with a lack of vitamin B12 or folic acid was constant. Determination of serum vitamin B12 was low in all cases while folic acid levels were within standards. Immuno- logically it was found in all patients, a positivity of anti-intrinsic factor antibody and/or anti- parietal cells antibody at rates up to 67 times over normal ranges. Pernicious anemia was associated with autoimmune thyroid dysfunction in 4 patients. It was two cases of Hashimoto thyroiditis at hypothyroidic phase (high TSHus, thyréoperoxydase anti-antibody positive (over 10 N) in both cases and Graves’ disease in the two other cases. Pernicious anemia was associated with a syndrome of primary antiphospholipid antibody in a case. Furthermore pernicious anemia was found in a patient autoimmune type 1 diabetes with strongly positive anti -GAD antibodies and rheumatoid arthritis by retaining it in the diagnosis of multiple autoimmune syndrome. Conclusion: These cases illustrate the existence of the association of pernicious anemia with other autoimmune diseases in our context. This should encourage practitioners to seek hided autoimmune diseases when they consider the diagnosis of pernicious anemia.

Research Progress of Vitamin D and Autoimmune Diseases

As a fat-soluble vitamin,Vitamin D is a necessary hormone to maintain normal physiological activities of the body.In recent years,vitamin D has been considered as a new neuroendocrine-immunomodulatory hormone,and researchers have paid more attention to the study of immune regulatory mechanism.It is not only related to calcium and phosphorus metabolism,bone metabolism and other important metabolic mechanisms of the body,but also closely related to the immune regulation mechanism of the body.Vitamin D deficiency caused by many factors can play a certain role in the development of autoimmune diseases.In this paper,the related mechanisms of vitamin D affecting autoimmune diseases were reviewed,with a view to expound the close correlation between vitamin D and autoimmune diseases,so as to find new diagnosis and treatment approaches for clinical autoimmune diseases and improve the quality of life of patients with autoimmune diseases.

Studies on the Inactivated Oil Emulsion Binary Vaccine against Newcastle Disease and Fowl Cholera(Ⅲ)——Safety and Immune Efficacy Test of Vaccine on Duck and Goose

[Objective] The aim of this study is to provide theoretical basis for immunizing waterfowls(duck and goose)with the inactivated oil emulsion binary vaccine against Newcastle Disease(ND)and Fowl Cholera(FC).[Method]Bacterial liquid from solid culture media inoculated avian Pasteurella multocida(APM)type A and allantoic fluid from embryonic eggs infected with Newcastle Disease Virus(NDV)attenuated strain La Sota were mixed and inactivated by formalin to prepare 5 batches of inactivated oil emulsion binary vaccine,which were then used for the safety and immune efficacy test on duck and goose.[Result]Immunized ducks and geese didn't performed any adverse reactions in the safety test of the 5 batches of vaccine;the immune efficacy test showed that ND-HI antibody titers of ducks and geese were no less than 4 log2 three weeks after inoculation,and the protection rates against NDV and APM were 100% and 66.7%-83.3%,respectively.[Conclusion]The binary vaccine against ND and FC is safe and reliable for duck and goose,and can provide them with sufficient immunity protection against ND and FC.

Cause of Autoimmune Diseases： Anomalous Magnetic Fielads

The aim of this work is to prove the AMF （anomalous magnetic fields） from the environment cause of AID （autoimmune diseases）. The therapeutic possibilities of natural EMF （Earth＇s magnetic field） is pointed out and how to act to prevent AID is determined. Authors indicate in which magnetic fields the IS （immune system） defends the body. They also explain why, in medical literature, risk factors are mistakenly declared pathogens of AID. The magnetic fields intensity in 20 peoples＇ beds, suffering from Type 1 diabetes, was measured with proton magnetometer （accuracy of 100 nT）. The measurement results are presented on sketches, patients were transferred to the natural EMF, medical condition was monitored, and AID function IS ethiopathology was studied. The correlation between AMF and organ location where AID occurred was determined by measuring. The cells of an organism, formed in natural EMF, are in magnetic balance. When an intruder enters the body, magnetic balance disappears and leukocytes with its MF （magnetic forces） destroy intruders. In the AMF, cells get enlarged MF without magnetic balance, causing IS with its MF to attack own cells, resulting AID. When an intruder enters a tissue, tissue cells and cells of intruders gain enhanced MF. IS with its MF destroys intruders. In the literature （The China Study by T. Colin Campbell）, the food is presented as cause of number of diseases. It was found what led to such a misinterpretation. It has been proven that causes of mentioned diseases are only AMF, which can be located in any organ, and with Type 1 diabetes its spread to the whole body with strongest intensity on pancreas. AMF give tissue cells reinforced MF without magnetic balance causing IS to deplete own tissues, resulting AID. IS works perfectly without AMF and risk factors are only a consequence of AMF.

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.