Effect of Icariin on Peripheral Blood Dendritic Cells and Th17/Treg Balance in Myocardial Remodeling Model of Dahl Salt-sensitive Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of icariin （ICA）-mediated vitamin D system on peripheral blood dendritic cells （DCs） and helper T cells 17 （Th17）/regulatory T cells （Treg） balance in myocardial remodeling model of Dahl salt-sensitive rats. MethodFifty SPF Dahl salt-sensitive rats were divided into model group， vitamin D group （3×10-5 mg·kg-1·d-1）， and high-， medium-， and low-dose ICA groups （120， 60， 30 mg·kg-1·d-1）， and 10 Dahl salt-resistant rats were used as normal group. The myocardial remodeling model was established by feeding rats with a high-salt diet containing 8% NaCl. After six weeks of modeling， the normal group and the model group were given an equal volume of ultrapure water by gavage， and other groups were continuously administrated for six weeks. Cardiac echocardiography， hematoxylin-eosin （HE） staining， and Masson staining were used to observe the pathological changes in cardiac structure and fibrosis. The levels of serum 25（OH）D3， B-type N-terminal pro-brain natriuretic peptide （NT-ProBNP）， interleukin （IL）-17， transforming growth factor （TGF）-β1， IL-12， and IL-10 were detected by enzyme-linked immunosorbent assay （ELISA）. The phenotype of peripheral blood DCs and the ratio of Th17/Treg cells of rats were detected by flow cytometry. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expressions of vitamin D receptor （VDR），1α-hydroxylase （CYP27B1）， and 24-hydroxylase （CYP24A1） in peripheral blood DCs of rats. ResultCompared with the control group， the rats in the model group had pathological changes such as disordered arrangement of myocardial cells and cytoplasmic hypertrophy and swelling. Myocardial collagen fibers proliferated significantly， and the arrangement of myocardial fibers was disordered. The levels of serum 25（OH）D3 and IL-10 were significantly decreased， and the levels of serum IL-17， TGF-β1， IL-6， IL-12， and NT-ProBNP were significantly increased （P<0.05）. The costimulatory molecules CD40， CD80， CD86， and MHC-Ⅱ were highly expressed in the peripheral blood DCs， and the expression of CD11 and CD11b was lower （P<0.05）. The proportion of Th17 cells in the peripheral blood was significantly increased， and the proportion of Treg cells was decreased. The ratio of Th17/Treg was increased （P<0.05）. The mRNA and protein expressions of CYP24A1 in peripheral blood DCs increased， and the mRNA and protein expressions of CYP27B1 and VDR decreased （P<0.05）. Compared with the model group， the arrangement of myocardial fibers in each drug administration group was relatively regular， and the swelling of myocardial cells was significantly reduced. The pathological morphology of myocardial tissue was improved to varying degrees. The pathological changes in myocardial tissue were improved and alleviated to varying degrees. The drug could reduce the serum levels of NT-ProBNP， IL-17， TGF-β1， IL-6， and IL-12 and increase the level of serum 25（OH）D3 and IL-10 （P<0.05）. The expression of costimulatory molecules CD40， CD80， CD86， and MHC-Ⅱ in the peripheral blood DCs of rats was decreased， and the expression of CD11 and CD11b molecules was increased （P<0.05）. The drug could reduce the proportion of Th17 cells in peripheral blood and the ratio of Th17/Treg cells and increase the proportion of Treg cells （P<0.05）. It could decrease the mRNA and protein expressions of CYP24A1 in peripheral blood DCs of rats and elevate the mRNA and protein expression of VDR and CYP27B1 （P<0.05）. ConclusionICA can regulate the phenotype of peripheral blood DCs and the ratio of Th17/Treg cells by regulating the vitamin D system and play a role in improving myocardial remodeling from the perspective of immune balance.

Exploring Mechanism of Different Processed Products of Baiyaojian and Its Formula in Treating Ulcerative Colitis Based on Serum Metabolomics and Flow Cytometry / 中国实验方剂学杂志

ObjectiveTo explore the potential mechanism of different processed products of Baiyaojian and its compound Xiangmei pills in rats with ulcerative colitis（UC） by comparing the pharmacodynamic and metabolomic differences. MethodEighty SD rats were acclimatized and kept for 3 d， and randomly divided into 8 groups［blank group， model group， mesalazine group（0.4 g·kg-1）， Baiyaojian group（1.89 g·kg-1）， stir-fried Baiyaojian group（1.89 g·kg-1）， carbonized Baiyaojian group（1.89 g·kg-1）， and Xiangmei pills low and high dose groups（1.89， 5.67 g·kg-1）］， with 10 rats in each group. Rats in the blank group were administered physiological saline by gavage， and rats in the remaining 7 groups were orally administered 5% dextran sodium sulfate（DSS） solution daily for 8 consecutive days to induce UC model. After successful modeling， each dosing group was given the corresponding dose of drug solution by gavage， and the blank and model groups were given equal amounts of saline by gavage， and the drug was administered continuously for 8 d. Then serum levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-6， IL-10 and IL-1β were measured by enzyme-linked immunosorbent assay（ELISA）， hematoxylin-eosin（HE） staining was used to observe the histopathological changes of colon tissue， the proportion of T helper 17 cells（Th17） and regulatory T cells（Treg） in the peripheral blood of rats in each group was detected by flow cytometry. The endogenous metabolites in serum of rats were detected by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites were characterized by combining principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， and were analyzed according to the variable importance in the projection（VIP） value>1.0 and P<0.05， and potential metabolic pathways were analyzed according to Human Metabolome Database（HMDB）. ResultCompared with the blank group， the colon tissue of the model group was congested and the mucosa was ulcerated， the colon length was significantly reduced（P<0.01） and the quality was significantly increased（P<0.05）， the proportion of Th17/Treg in the peripheral blood and the serum levels of TNF-α， IL-6 and IL-1β were significantly increased， while the IL-10 expression wassignificantly reduced（P<0.05， P<0.01）. Compared with the model group， the colon tissue of UC rats in each treatment group was improved with scattered ulcers， reduced inflammatory cell infiltration， significantly increased colon length， and significantly decreased mass（P<0.05）， the proportion of Th17/Treg in the peripheral blood decreased， the expression of TNF-α，IL-6 and IL-1β was significantly reduced（P<0.05， P<0.01）， while the IL-10 expression was significantly increased（P<0.01）. The therapeutic effect of different administration groups on UC was in the order of high dose group of Xiangmei pills>low dose group of Xiangmei pills>carbonized Baiyaojian group>stir-fried Baiyaojian group>Baiyaojian group. And a total of 26 differential metabolites were screened in the metabolomics results. Compared with the blank group， 14 differential metabolites were up-regulated and 5 metabolites were down-regulated in the model group， and 14， 9， 14， 12 and 17 metabolites could be recalled in the Baiyaojian group， stir-fried Baiyaojian group， carbonized Baiyaojian group， Xiangmei pills low and high dose groups. The main metabolic pathways involved were citrate cycle pathway， pantothenic acid and coenzyme A biosynthesis pathway， aromatic hydrocarbon receptor（AhR） signaling pathway， glycolysis/gluconeogenesis pathway. ConclusionThe therapeutic effect of Baiyaojian on UC is significantly improved after charcoal stir-frying， and the efficacy is more prominent when combined with Angelicae Dahuricae Radix and Mume Fructus Carbonisata， which can provide a basis for the development of Baiyaojian compound preparations.

Relationship between serum lncRNA XIST and SIRT1 levels with diabetic retinopathy and their diagnostic value / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To detect the expression levels of long non-coding RNA(lncRNA)X-inactive specific transcript(XIST)and silencing information regulatory factor 2 associated enzyme 1(SIRT1)in serum of patients with type 2 diabetes mellitus(T2DM), and to explore their correlation with diabetic retinopathy(DR)and their diagnostic value. METHODS: Prospective study. A total of 214 patients with T2DM admitted to our hospital from January 2022 to February 2023 were selected as the research subjects. Based on whether retinopathy occurred, they were divided into 126 cases(126 eyes)in the non-DR group and 88 cases(88 eyes)in the DR group. An additional 130 healthy individuals who underwent a physical examination during the same period were selected as the control group. The serum levels of lncRNA XIST and SIRT1 in the three groups were measured and compared. The relationship between lncRNA XIST and SIRT1 expression with DR was analyzed using Pearson's method. The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum lncRNA XIST, SIRT1, and their combination for DR. Multivariate Logistic regression analysis was performed to investigate the factors affecting the occurrence of DR in T2DM patients.RESULTS: Compared with the control group, the levels of serum lncRNA XIST and SIRT1 in the non-DR group and DR group were successively decreased(all P&#x003C;0.05). The levels of serum lncRNA XIST and SIRT1 were positively correlated in DR patients(r=0.639, P&#x003C;0.05). ROC analysis showed that the area under the curve(AUC)for predicting DR by combining serum lncRNA XIST and SIRT1 was 0.940, which was higher than the AUC by serum lncRNA XIST and SIRT1 alone(0.855, 0.875). Logistic regression analysis showed that lncRNA XIST(OR=0.752)and SIRT1(OR=0.694)were influencing factors for the occurrence of DR(both P&#x003C;0.01).CONCLUSION: The serum levels of lncRNA XIST and SIRT1 are both lower in DR patients, and the combination of lncRNA XIST and SIRT1 has a better assessment capacity for the occurrence of DR.

Development and application of regulatory T cells in corneal transplant rejection / 国际眼科杂志(Guoji Yanke Zazhi)

Corneal transplantation is an effective treatment for corneal blindness, and it is the only hope for patients with corneal blindness. Cornea has no blood vessels and no lymphatic vessels, which is called immune privilege organ, so the success rate of corneal transplantation is significantly higher than that of other organ transplantation, but the rejection reaction after corneal transplantation is still the main reason for the failure of corneal transplantation. The directional movement of immune cells to lymphoid tissue and inflammatory sites is the mainly immune response after organ transplantation. And the regulatory T cells(Treg)play a key role in immune regulation, which can induce immune tolerance by regulating and inhibiting the activation of effector T cells and reduce the rejection reaction after corneal transplantation. In addition, this review also discussed the effectiveness of applying cordyceps sinensis extract FTY720 to enhance the function of Treg. Based on this, we briefly reviewed the sources, mechanism of action and treatment of Treg after corneal transplantation, so as to provide some reference for the subsequent clinical application transformation and basic research.

Mechanism of action of sterol regulatory element-binding proteins in nonalcoholic fatty liver disease and related therapeutic targets / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） has become the most common liver disease in the world and is an important risk factor for the progression to hepatocellular carcinoma. However， the pathogenesis of NAFLD remains unclear， and there is still a lack of specific treatment measures. Sterol regulatory element-binding proteins （SREBP） are an important nuclear transcription factor， which mainly maintains the balance of lipid metabolism inside the body by activating the genes associated with the synthesis and uptake of cholesterol， fatty acids， and triglycerides， and therefore， SREBP are a target for the treatment of metabolic diseases. This article reviews the latest advances in SREBP in the pathogenesis of NAFLD and the latest evidence of SREBP-targeted therapy for NAFLD. It is worth noting that recent studies have shown that SREBP inhibition can cause liver injury together with autophagy damage. Therefore， excessive inhibition of lipogenesis may exert a counterproductive effect on the treatment of NAFLD. In conclusion， SREBP is a promising therapeutic target for NAFLD； the molecular mechanism of SREBP in lipid metabolism is regulated by many factors， and these factors are being deeply explored and analyzed， which has an important clinical significance for the treatment of NAFLD.

Mechanism of action of follicular helper T cells in autoimmune hepatitis / 临床肝胆病杂志

Autoimmune hepatitis （AIH） is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system， and with the prolongation of disease course， it may gradually progress to liver cirrhosis and even hepatocellular carcinoma. Although great achievements have been made in the understanding and treatment of AIH， its etiology and pathogenesis still remain unclear. T cells play a crucial role in the development and progression of AIH， and by focusing on follicular helper T cells， this article elaborates on the research advances in follicular helper T cells in AIH， in order to provide new ideas and strategies for the clinical treatment of AIH.

Vitamin D Plays a Crucial Role in Regulating Dopamine Nervous System in Brain / 生物化学与生物物理进展

Vitamin D is a unique fat-soluble vitamin that plays an indispensable role in human health. It exists in various forms, the most significant being vitamin D2 (derived from plant sources) and vitamin D3 (synthesized naturally in human skin upon exposure to sunlight). Vitamin D’s primary function is to facilitate the absorption of calcium and phosphorus, which are crucial for maintaining healthy bones. Beyond its role in bone health, vitamin D significantly influences the immune system, muscle function, cardiovascular health, and the regulation of brain functions. A deficiency in vitamin D can lead to various chronic diseases such as rickets, osteoporosis, decreased immunity, increased risk of mental disorders, and cancers. The synthesis of vitamin D in the human body, both peripherally and centrally, relies on sunlight exposure, dietary sources, and various supplements. As a neuroactive steroid, vitamin D impacts both the physiological and pathological processes of the nervous system and plays a key role in brain health. It profoundly affects the brain by regulating neurotransmitter synthesis and maintaining intracellular calcium balance. As an essential chemical molecule, vitamin D participates in complex signal transduction pathways, impacting neurotransmitter functions and synaptic plasticity. Vitamin D’s role in regulating dopamine (DA)—a neurotransmitter critical for motivation, reward perception, and other higher cognitive functions—is particularly noteworthy. Recent studies have revealed that vitamin D not only promotes the synthesis of DA but also plays a role in regulating DA levels within the brain. It exerts neuroprotective effects on DA neurons through anti-inflammatory, antioxidant actions, and neurotrophic support, thereby creating an optimal environment for DA neurons, influencing neuronal structure, and affecting the movement of calcium ions within nerve cells, positively impacting the overall health and functionality of the DA system. Furthermore, vitamin D can regulate the synthesis and release of DA, thus affecting the signal transmission of various DA neural projection pathways in the brain. This function is vital for understanding the complex interactions between neural mechanisms and their effects on key behaviors and cognitive functions. This review aims to delve deeply into the synthesis, metabolism, and pathways of vitamin D’s action, especially its regulatory mechanisms on DA neurons. Through this exploration, this article seeks to provide a solid theoretical foundation and research framework for a deeper understanding of vitamin D’s role in motivation and reward behaviors. This understanding is crucial for appreciating the broader significance of vitamin D in the fields of neuroscience and neurology. In summary, research and discoveries regarding vitamin D’s impact on the nervous system highlight its importance in neural health and function. These insights not only enhance our understanding of the complex workings of the nervous system but also open new avenues for the prevention and treatment of neurological diseases. The exploration of vitamin D’s multifaceted roles offers promising prospects for developing new therapeutic strategies, underscoring the compound’s potential in addressing a range of neural dysfunctions and diseases. As research continues to evolve, the profound implications of vitamin D in the field of neurology and beyond become increasingly apparent, marking it as a key target for ongoing and future scientific inquiry.

Correlation analysis of serum Chemerin with disease activity and Th17/Treg in patients with rheumatoid arthritis / 天津医药

Objective To explore the correlation of serum Chemerin level with disease activity and the ratio of T helper 17/regulatory T cells(Th17/Treg)in patients with rheumatoid arthritis(RA).Methods A total of 180 patients with RA who were admitted to our hospital were regarded as the observation group.According to the DAS28 score,the observation group was divided into the high activity group(60 cases),the moderate activity group(60 cases)and the low activity group(60 cases).Another 180 healthy people who underwent physical examination in our hospital during the same period were regarded as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of Chemerin,interleukin-9(IL-9),interleukin-10(IL-10)and interleukin-17(IL-17).Flow cytometry was used to detect the Th17/Treg ratio.Spearman correlation analysis was applied to analyze the correlation between serum Chemerin level and DAS28 score.Pearson correlation analysis was used to analyze the correlation between serum Chemerin level and Th17,Treg cell percentage and Th17/Treg ratio.Results The results of this study showed that the serum level of Chemerin was higher in the observation group than that in the control group(P＜0.05).The serum Chemerin level was positively correlated with DAS28 score(P＜0.05).Serum Chemerin levels and DAS28 scores decreased in turn in the high,moderate and low activity groups(P＜0.05).The percentage of Th17 cells and the ratio of Th17/Treg were higher in the observation group than those in the control group,and the percentage of Treg cells was lower in the observation group than that in the control group(P＜0.05).The level of IL-10 was lower in the observation group than that in the control group,while levels of IL-17 and IL-9 were higher in the observation group than those in the control group(P＜0.05).The results of Pearson correlation analysis showed that serum Chemerin level was positively correlated with the percentage of Th17 cells and the ratio of Th17/Treg,and negatively correlated with the percentage of Treg cells(P＜0.05).Conclusion Serum Chemerin level is elevated in patients with RA,which is closely related to disease activity and Th17/Treg ratio.

Therapeuti ceffect and potential mechanism of cholesterol sulfate on a mouse model of Hashimoto's thyroiditis / 西安交通大学学报(医学版)

Objective To investigate the therapeutic effect of cholesterol sulfate(CS)on the Hashimoto's thyroiditis mouse model.Methods Female NOD.H-2h4 mice were fed with 0.05％NaI in different periods and treated with CS by intraperitoneal injection for two consecutive weeks.HE staining was used to visualize and score the degree of lymphocyte infiltration in the thyroid;serum levels of thyroglobulin antibody(TgAb),thyroid peroxidase antibody(TPOAb),thyroxine(T4),and thyroid stimulating hormone(TSH)were detected by ELISA.The proportions of B cells and Treg,Th17,Th1,and Th2 cells were analyzed by immunofluorescence staining flow cytometry.Results HE staining showed that the inflammatory score of thyroid tissue in mice after intraperitoneal injection of CS in the 8-week group and the 16-week group decreased significantly(P＜0.05).In the 64-week group,there was no significant difference between the treatment group and the induction group(P=0.31).Serological analysis showed that after CS intervention,the levels of TgAb and TPOAb in mice induced by 0.05％NaI significantly lowered(P＜0.05)in the 8-week group and the 16-week group,while thyroid function(TSH and T4 levels)of the mice changed significantly only in the 16-week group.Flow cytometry analysis showed that in the 8-week group,after CS intervention the proportions of B lymphocytes and Th1,Th2,Th17 and Treg cells in mice were significantly changed(P＜0.05).Conclusion CS has significant therapeutic and remission effects on the early and middle stages of Hashimoto's thyroiditis.

The role of BMAL1 and MyoD in exercise-induced skeletal muscle damage / 中国组织工程研究

BACKGROUND:A high-load exercise can trigger the degradation of titin,leading to skeletal muscle damage.MyoD participates in skeletal muscle generation and plays an important role in the repair of skeletal muscle damage. OBJECTIVE:To observe the expression changes of MyoD,BMAL1 and titin in skeletal muscles at different times during a high-load exercise,as to clarify the role of MyoD and BMAL1 in exercise-induced skeletal muscle damage. METHODS:Twenty-four 8-week-old Sprague-Dawley rats were randomly divided into a control group(n=4)and an exercise group(n=20).Rats in the exercise group were subjected to downhill running(90 minutes).Soleus muscle samples were collected at 0,12,24,48,and 72 hours after exercise.The mRNA expressions of BMAL1 and MyoD were measured by real-time fluorescence quantitative PCR.The ultrastructure of skeletal muscle fibers was observed by transmission electron microscope.Immunofluorescence was used to observe the co-localization of MyoD and BMAL1 as well as BMAL1 and titin. RESULTS AND CONCLUSION:After the single high-load centrifugal exercise,the sarcomere of the soleus muscle was widened and the Z-line was blurred and water wave-like,both of which were most serious at 12 hours after exercise and basically recovered at 72 hours.The results of real-time fluorescent quantitative PCR showed that BMAL1 mRNA expression in the exercise group increased first and then tended to normal,while the mRNA expression of MyoD decreased first and then increased.Immunofluorescence co-localization observation indicated that the co-localization of BMAL1 and MyoD was obviously observed at 12 and 24 hours after exercise,and the co-localization of BMAL1 and titin was observed at 0,12,and 24 hours.All the findings indicate that MyoD and BMAL1 are jointly involved in the repair of exercise-induced skeletal muscle damage probably via titin.

Mechanisms of exercise-regulated telomere length and health promotion / 中国组织工程研究

BACKGROUND:As we age,the function of various systems in the human body gradually decreases and the telomeres,located at the ends of chromosomes,consequently shorten,leading to the development and progression of various chronic age-related diseases.As a cost-effective intervention,scientific exercise has been shown to reduce the rate of telomere wear,maintain telomere length,delay the aging process and reduce the probability of disease.At the same time,better health level is important for healthy aging. OBJECTIVE:To sort out the role of telomeres in health promotion by analyzing telomere and physical fitness,the common adverse factors of telomere length shortening and chronic disease occurrence,and the influence of telomere length on the regulation of the occurrence and development of common chronic diseases such as cardiovascular disease,cancer,diabetes,obesity and mental disease,as well as to summarize the possible regulatory mechanism of exercise regulating telomere length,and to explore the role of telomere in the regulation of exercise on the above-mentioned chronic diseases for the purpose of health promotion. METHODS:The search terms of"exercise,telomere,aerobic capacity,muscle strength,aging"in Chinese and English were used to search the relevant literatures in CNKI and PubMed,respectively.A total of 108 articles were included for final review. RESULTS AND CONCLUSION:In terms of physical fitness and health promotion,there is a strong correlation between the maximum aerobic exercise capacity and muscle strength of the human body and telomere length.Long-term physical exercise can enhance the level of physical fitness to maintain telomere length and promote the heath of the human body.In terms of chronic diseases and health promotion,abnormal telomere length can promote the occurrence of some chronic diseases such as cardiovascular diseases,cancer,diabetes,obesity,and mental diseases,and the factors that accelerate the shortening of telomere length,such as oxidative stress,inflammation,and telomerase activity,also have adverse effects on the development of these diseases.The regulation of telomere length by exercise can reduce the levels of oxidative stress and inflammation,improve the activity of telomerase and enhance the stability of telomere protein complex.Through these regulatory mechanisms,exercise slows the rate of telomere wear and maintains consistent telomere length,thereby reducing the risk of chronic diseases associated with abnormal telomere length,such as cardiovascular disease,cancer,diabetes,obesity,and mental diseases.Therefore,telomeres play a positive role when exercise is used to regulate related diseases and promote human health.

Bioinformatics analysis of m6A-associated genes in steroid-induced osteonecrosis of the femoral head / 中国组织工程研究

BACKGROUND:m6A modification has been confirmed to play an important role in the occurrence and development of osteonecrosis of the femoral head;however,the role of m6A modification patterns in steroid-induced osteonecrosis of the femoral head remains unknown. OBJECTIVE:Bioinformatics analysis was performed based on the Gene Expression Omnibus(GEO)database to analyze the differential expression of the m6A gene in steroid-induced osteonecrosis of the femoral head,predict the downstream targeted miRNAs,and investigate the potential pathogenesis. METHODS:Expressing profiles of mRNA data of steroid-induced osteonecrosis of the femoral head were downloaded from GEO database(GSE123568).Differentially expressed genes(DEGs),Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using the R software.After obtaining these differentially methylated m6A genes(m6A-DEGs),we analyzed GO function and KEGG pathway enrichment and compared the correlation among the m6A-DEGs typing according to gene expression.The protein-protein interaction network and core gene subnetwork of m6A-DEGs were constructed using Cytoscape software.The m6A-DEGs-associated potential miRNAs were predicted using the TargetScan,miRTarBase,and miRBD databases.Simultaneously,ChIPBase and hTFtarget databases were used to predict potential transcription factors of seven core genes,then m6A-miRNA and transcription factor-m6A regulatory networks were constructed separately.Finally,the expression levels of the seven core m6A-DEGs were verified by using the GSE74089 dataset. RESULTS AND CONCLUSION:(1)A total of 2 460 common DEGs were screened out from datasets,among which 1 455 genes were upregulated and 1 005 genes were downregulated.(2)A total of 14 m6A-DEGs were identified in the datasets.Among them,11 m6A-DEGs were up-regulated and 3 m6A-DEGs were down-regulated.Differential gene expression was considered significant for m6A-DEGs in steroid-induced osteonecrosis of the femoral head(P<0.05).Spearman correlation analysis showed a significant correlation between m6A-DEGs.(3)GO and KEGG enrichment analysis showed that m6A-DEGs were mainly enriched in myeloid cell differentiation and development,immune and cytokine receptor activity,osteoclast differentiation,AMPK signaling pathway and interleukin-17 signaling pathway.(4)The seven core genes of m6A-DEGs contained YTHDF3,YTHDF1,YTHDF2,ALKBH5,METTL3,HNRNPA2B1,and HNRNPC.A total of 44 miRNAs overlapping were detected in the miRTarBase,miRDB,and TargetScan databases.Totally 79 transcription factors overlapping were found in the ChIPBase and hTFtarget databases.(5)The expression levels of six core m6A-DEGs in the GSE74089 dataset were consistent with those in the GSE123568 dataset.(6)These findings confirm that the seven m6A-DEGs identified through bioinformatics techniques play a regulatory role in the expression of various miRNAs,transcription factors,AMPK,and interleukin-17 signaling pathways,and these genes have a significant impact on the differentiation and development of bone marrow cells as well as osteoclast differentiation in steroid-induced osteonecrosis of the femoral head.Consequently,these findings offer data support and establish a research direction for future investigations into the pathogenesis and targeted therapeutic strategies for steroid-induced osteonecrosis of the femoral head.

Regulation effect of dopamine on sepsis-associated macrophage functions and the mechanisms involved / 中国小儿急救医学

Sepsis is a life-threatening organ dysfunction caused by the host disordered response to infections.As one of the most important innate immune cells in the body，macrophages can maintain the immune homeostasis by recruiting other immune cells，clearing pathogens，presenting antigens，and play important regulatory roles in infectious diseases such as sepsis by releasing inflammatory factors.As a critical neurotransmitter，dopamine not only participates in the neurological processes such as learning and cognition，but also regulates the immune processes，including regulating the activation，proliferation and functional changes of immune cells such as neutrophils，lymphocytes，monocytes and macrophages.Current studies demonstrate that during the infection and inflammation process of sepsis，the phagocytosis，polarization，and release of inflammatory factors of macrophages are regulated by dopamine.This review summarized the recent research progress on the regulatory functions and the underlying mechanisms of dopamine on macrophages in sepsis.

Advances in the effect of inflammatory factors on immune mechanism of aplastic anemia / 新乡医学院学报

The pathogenesis of aplastic anemia(AA)is complex and associated with hematopoietic stem cell defect,abnormal bone marrow microenvironment,immune dysfunction,and somatic mutation,in which the immune mechanism plays an important role.This article reviews the pathogenesis of AA from the following aspects:regulatory T cell reduction,hematopoietic stem cell reduction caused by factor-related apoptosis/factor-related apoptosis ligand signaling pathway,aberrant target gene expression induced by inflammatory factor-stimulated microRNAs,and regulatory T cell dysfunction,so as to provide ideas and methods for clinical practice.

Research progress of microglia activation in the regulatory mechanism of ret-initis pigmentosa / 眼科新进展

Retinitis pigmentosa(RP)is a hereditary retinal degenerative ocular disease.Accumulating studies have demonstrated that microglia(MG)activation occurs at the early stage of retinal degeneration.MG,as immune cells in the central nervous system and retina,are involved in the formation of the front line of the innate immune system,exhibiting neuroprotective or neurotoxic effects in various neurodegenerative processes.The neurotoxic or neuroprotective effects re-sulting from microglia activation may influence the pathological progression of RP.Consequently,therapeutic strategies tar-geting MG,aiming to modulate disease progression and outcome by balancing neuroprotective or neurotoxic effects,repre-sent a promising avenue for future treatment.

Research progress in the endogenous regulatory factors of corneal lym-phangiogenesis and its related ocular surface diseases / 眼科新进展

Blood and lymphatic vessels are absent from the normal cornea.Pathological stimulation such as corneal in-fection,chemical burns and transplantation rejection can disrupt the balance between pro-and anti-lymphangiogenesis fac-tors,causing lymphatic vessels to extend from the corneal limbus to the central cornea.Corneal lymphangiogenesis is closely related to various regulatory factors and cellular signaling pathways.Further study and elucidation of the mechanism of corneal lymphangiogenesis will open up new directions for treating corneal transplantation rejection,inflammatory disea-ses,dry eyes and tumor metastasis.This review concludes the endogenous regulatory factors of corneal lymphangiogenesis and therapeutic strategies for its related ocular surface diseases.

Clinical analysis of contrast-enhanced ultrasound combined with serum SMURF1 detection in the diagnosis of thyroid cancer / 局解手术学杂志

Objective To investigate the diagnostic value of contrast-enhanced ultrasound(CEUS)combined with serum Smad ubiquitin regulatory factor 1(SMURF1)detection for thyroid cancer.Methods A total of 144 suspected thyroid cancer patients admitted to Lishui branch of Zhongda Hospital Affiliated to Southeast University from February 2019 to February 2020 were selected as the study subjects.Based on the histopathological results,they were divided into the thyroid cancer group(76 cases)and the benign group(68 cases).All patients underwent contrast-enhanced ultrasound examination and serum SMURF1 level detection;the diagnostic value of contrast-enhanced ultrasound parameters,serum SMURF1 detection alone,and the combination of the two methods for thyroid cancer were analyzed.Results Contrast-enhanced ultrasound parameters peak intensity(PI),mean perfusion intensity(SImean)and maximum perfusion intensity(SImax)in the thyroid cancer group were lower than those in the benign group,and the level of SMURF1 mRNA was higher than that in the benign group(P<0.05).The sensitivity of contrast-enhanced ultrasound parameter SImax in the diagnosis of thyroid cancer was 82.89%,the specificity was 72.06%,the accuracy was 77.78%,and the Kappa value was 0.552.The sensitivity of serum SMURF1 in the diagnosis of thyroid cancer was 65.79%,the specificity was 94.12%,the accuracy was 79.17%,and the Kappa value was 0.589.The sensitivity,specificity,accuracy and Kappa value of SImax combined with serum SMURF1 in the diagnosis of thyroid cancer were 97.37%,85.29%,91.67%and 0.832,respectively,which were higher than those of SImax and SMURF1 alone(P<0.05),the AUC of the combination of the two methods was 0.927,which was significantly higher than that of the two methods alone(Zcombined vs.SImax=3.999,P<0.001;Zcombined vs.SMURF1=3.270,P=0.001).Conclusion Contrast-enhanced ultrasound combined with serum SMURF1 detection can improve the diagnostic efficiency of thyroid cancer,which may avoid the over-diagnosis on the premise of ensuring the effective diagnosis of thyroid cancer patients.

lncRNA-mediated ceRNA network molecular mechanisms on ischemic stroke / 中国康复医学杂志

Objective:To construct the regulatory network of competitive endogenous RNA(ceRNA)and explore the mo-lecular mechanism of ischemic stroke(IS)by using bioinformatic analysis to screen the differentially-expressed genes. Method:The expression profiles of miRNA,mRNA and lncRNA in IS were downloaded from the NCBI GEO database.Differentially-expressed miRNAs,lncRNAs,and mRNAs were identified by the limma package in R software.The prediction of the relationship of lncRNA-miRNA and miRNA-mRNA were performed by starBase,miRDB and miRwalk databases.The results of prediction and differential analysis were taken to inter-sect and screened out differentially-expressed target mRNA(DETmRNAs),Kyoto Encyclopedia of Genes and Genomes(KEGG)and gene ontology(GO)enrichment analysis was performed by using the DAVID database.The protein-protein interaction(PPI)network was constructed by using the STRING database and the core tar-get genes in the network were identified by Cytoscape software. Result:A total of 20 differentially-expressed miRNAs,1512 lncRNAs,and 278 mRNAs were identified,and a ceRNA network was successfully constructed with the interactions of 5 lncRNAs-6 miRNAs-102 mRNAs in IS.The 285 DETmRNAs functions are mostly involved in the biological process such as chromatin organization,negative regulation of phosphoprotein phosphatase activity,or cell cycle.KEGG mainly enriched the signaling pathway including leukocyte trans-endothelial migration and platelet activation.The top 10 core genes were CREB1,MAPK1,GSK3B,SP1,PIK3R1,NR3C1,NCOR1,NFATC1,SETD2,and NSD1. Conclusion:The construction of the ceRNA network can help to further understand the molecular mechanism of IS and screen potential biomarkers,providing clues to further define rehabilitation targets and develop reha-bilitation strategies.

Endoplasmic reticulum stress induced immunosuppressive effects / 中国免疫学杂志

Endoplasmic reticulum stress(ERS)is a subcellular pathological state formed by imbalance of environment in endoplasmic reticulum,and is regarded as an important pathway that mediates apoptosis.Recent studies have found that after ERS occurs in various immune tissues and cells,immunosuppressive effect that produced is involved in regulating body's immune homeo-stasis,affecting occurrence,outcome and prognosis of many diseases.This article reviews production of ERS,signal regulation and pathophysiological changes in immune organs and immune cells,and its role in development of inflammatory diseases and tumors.

Analysis of influencing factors and pathway of self-regulatory fatigue in maintenance hemodialysis patients / 中华护理杂志

Objective Based on the process theory of stress effect,the structural equation model of the influencing factors of self-regulatory fatigue in maintenance hemodialysis patients is constructed,which provides theoretical bases and references for the formulation of intervention programs to relieve self-regulatory fatigue in patients.Method A total of 420 maintenance hemodialysis patients were surveyed using General Information Questionnaire,Self-Regulatory Fatigue Scale,Dialysis Symptom Index,Life Orientation Test-Revised,Perceived Social Support Scale,Brief Illness Perception Questionnaire and Medical Coping Styles Questionnaire.Results Total score of self-regulatory fatigue in maintenance hemodialysis patients was(49.52±10.93),and self-regulatory fatigue showed significant positive correlation with symptom distress,the illness perception,avoidance coping style,yieldly coping(r=0.476,0.428,0.303,0.611,all P＜0.01);self-regulatory fatigue showed significant negative correlation with perceived social support and dispositional optimism(r=-0.410,-0.652,all P＜0.01);it showed no significant correlation with facing coping(r=-0.032,P＞0.05).The Bootstrap analysis revealed that the mediation effect of yielding coping,dispositional optimism,perceived social support,and illness perception between symptom distress and self-regulatory fatigue was significant(95％CI:0.027～0.203).The overall effect of symptom distress on self-regulatory fatigue was(P＜0.001,95％CI:0.576～0.751);the direct effect was(P＜0.001,95％CI:0.170～0.357);the indirect effect was(P＜0.001,95％CI:0.332～0.485);the mediation effect accounted for 61.1％of the total effect value.Conclusion Maintenance hemodialysis patients have a high degree of self-regulatory fatigue,which needs to be further improved.Medical staff should timely identify and evaluate the symptom distress of patients,focus on guiding patients to adjust optimistic disease,provide patients with psychological guidance and stress coping strategies,reduce the negative coping behavior tendency,guide the patients correctly perceive support and care in social relations,help patients set up the correct disease cognition,thus reducing the patient's self-regulatory fatigue.