Study on the relationship between intestinal flora analysis and CD4 +T lymphocyte subsets in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To explore the characteristics of intestinal microbiota in patients with systemic lupus erythematosus (SLE), and further explore the relationship between microbiota and CD4 +T lymphocyte subsets and disease activity. Methods:Fecal samples were collected from 96 patients with SLE, and 96 sex- and age-matched healthy controls (HCs). The gut microbiota were investigated via 16s rRNA sequencing. Flow cytometry was used to detect peripheral CD4 +T lymphocyte subsets of Th1, Th2, Th17 and Treg cells. Indicators of disease activity such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3 and C4, Systemic lupus erythematosus disease activity index(SLEDAI) for each patient were recorded. Differential abundance analysis was carried out using the edgeR algorithm. The Wilcoxon rank-sum test was used to compare alpha diversity indices, bacterial abundances, and the F/B ratio between groups. R (version 4.0.1) was used for comparative statistics, and Pearson′s correlation analysis was used to assess the correlations between the relative abundances of bacterial genera and serum levels of ESR, CRP, C3 and C4 in the samples. Results:The alpha estimators of richness (ACE and Chao 1) were significantly reduced in SLE feces samples compared with those of HCs ( P<0.01). Bacterial diversity estimators, including the Shannon ( P<0.01) and Simpson′s ( P<0.01) indices, were also significantly lower in SLE. Significant differences in gut microbiota composition between SLE and HCs were found using the edgeR algorithm. Compared with HC, 24 species of bacteria were significantly different in SLE patients at the genus level ( P<0.05). Moreover, there was a significant positive correlation between CRP and Coprococcus ( r=0.30, P=0.014), C4 and Corynebacterium ( r=0.31, P=0.013) and Faecalibacterium( r=0.25, P=0.048), Hemoglobin and Morganella( r=0.41, P=0.001), as well as SLIDA and Corynebacterium( r=0.25, P=0.047). In terms of lymphocyte subsets, there was significant positive correlation between B cells, Treg cells and Eubacterium eligens group, as well as CD8 +T, CD4 +T, NK cells and Corynebacterium. In additional, Th1 was positively correlated with Shigella Escherichia coli ( r=0.52, P=0.008), and Th2 was positively correlated with Dielma ( r=0.51, P<0.001). Conclusion:The abundance and diversity of intestinal flora in SLE patients were significantly reduced, and the differentially expressed bacteria were closely related to the CD4 +T lymphocyte subsets and disease activity indicators of patients.

The proportion of Th17 cells in patients with systemic sclerosis: a Meta-analysis / 中华风湿病学杂志

Objective:To clarify peripheral Th17 level in SSc patients and its correlation with disease.Methods:Chinese databases CNKI, CBM, Wanfang and VIP, and English databases PubMed, EMBASE, Web of Science, Cochrane Library and Science Direct were searched to collect a case-control study on the content of Th17 cells in peripheral blood of patients with SSc. The papers published when the database was first developed in 25 February 2021. Meta-analysis was conducted using Stata 12.0 software, and I2 and Egger tests were used to evaluate the heterogeneity and publication bias between studies. Results:A total of 26 case-controls were included in the study, including 1 160 patients with SSc and 778 healthy controls. Overall, the percentage of Th17 cells in SSc patients was higher than in healthy controls [SMD(95% CI)=1.85 (1.33, 2.38), P<0.001], which was most significant in IL-17 +Th17 concentration [SMD(95% CI)=1.88 (1.28, 2.48), P<0.001]. As for disease activity, the proportion of Th17 cells in active SSc patients was much higher than those of patients in remission [SMD(95% CI)=1.92 (1.12, 2.71), P<0.001]. SSc patients had a reduced Th17 level after receiving DMARDs treatment [SMD(95% CI)=-0.74 (-1.05, -0.42), P=0.029]. Conclusion:The number of Th17 cells increase significantly in the peripheral blood of patients with SSc, and is related to disease activity. DMARDs can be used to treat this disease by downregulating Th17 levels.

Research progress in the role of endoplasmic reticu-lum stress in cerebral ischemia-reperfusion injury / 中国药理学与毒理学杂志

During cerebral ischemia-reperfusion injury(CIRI),endoplasmic reticulum stress(ERS)leads to the development and progression of a series of deleterious physiological responses such as oxidative stress,dis-turbed calcium ion homeostasis,inflammation,apoptosis and autophagy.The unfolded protein response(UPR)is the main pathway activated by ERS,which regulates the expression of related factors within the endoplasmic reticu-lum(ER)and reduces protein translation levels.Prolonged and intense ERS may lead to cell death.Excessive ERS induces apoptosis mediated by C/EBP homologous pro-tein(CHOP),caspase-12 and c-Jun N-terminal kinase(JNK),thereby exacerbating brain damage.The thresh-old for the transition from adaptive mechanisms to apop-totic mechanisms during ERS depends on multiple fac-tors,including the cell status and environment,signaling pathway activity status,cumulative cascade,and the dose and time of ERS inducers.Further research is needed to completely elucidate the mechanism of ERS.Although the factors associated with the PERK and ATF6 path-ways are less extensively studied,their regulators still exist.Deficiency of protein tyrosine phosphatase 1B(PTP1B)leads to increased phosphorylation of PERK-eIF2α,while regulation of the proteasome and regulation of the XBP1 target gene WFS1 may also affect ATF6 sta-bility.In addition,differences in the structure,gene expres-sion,and metabolism of different types of neurons,as well as in their internal environment,may lead to differ-ences in their response to and impact on ERS.Differenc-es in UPR signaling pathways occur in hippocampal neurons and medial thalamic cells,and Purkinje cells and pyramidal cells may be more sensitive to ERS than other types of neurons.Our group's previous study found that ERS induced apoptosis in neurons after the onset of CIRI by regulating proteins such as GRP78,CHOP and caspase-12,but the effects of UPR activation on different cells need to be further investigated.

Investigation on endoplasmic reticulum stress mech-anism of ischemic stroke based on network pharma-cology / 中国药理学与毒理学杂志

OBJECTIVE To investigate the mecha-nism of endoplasmic reticulum stress in cerebral isch-emic stroke from a theoretical perspective based on net-work pharmacology.METHODS GeneCards and OMIM databases were used to screen out the related targets of cerebral ischemic stroke and endoplasmic reticulum stress.And Venny2.1.0 was used to draw Venn's diagram to get the intersecting genes between cerebral ischemic stroke and endoplasmic reticulum stress.String data-base was used to get the protein-protein interaction(PPI)diagram and cytoscape was used for visualization analy-sis.The key genes were screened out by cytohubba plug-in,and enrichment analysis was performed.RESULTS Network pharmacology showed that there were 3744 cerebral ischemic stroke-related targets and 8675 endo-plasmic reticulum stress-related targets.After screening,41 common targets were got.There were 37 nodes,390 edges in the PPI network,namely,there were 37 interact-ing proteins and 390 interacting relationships.The key genes identified by cytohubba plug-in were IL-6,ALB,INS,TNF,AKT1,CASP3,MAPK3,TP53,SIRT1 and VEGF.The biological process involves reaction to oxida-tive stress,the regulation of neuron death,and negative regulation of cell differentiation,etc.;cellular components were related to the membrane raft,smooth endoplasmic reticulum,endoplasmic reticulum lumen and other com-ponents;molecular function aspects were related to sig-naling receptor activator activity,chaperone binding and protease binding.Enrichment analysis of pathway revealed that the intersecting targets were involved in PI3K/Akt pathway and protein processing in endoplasmic reticulum,etc.CONCLUSION The endoplasmic reticu-lum stress in cerebral ischemic stroke is related to the bi-ological processes of reaction to oxidative stress,the reg-ulation of neuron death,and negative regulation of cell differentiation,the mechanism may be related to neuroin-flammation and apoptosis.

Research progress on the mechanism of action of endoplasmic reticulum stress inhibitors / 中国药理学与毒理学杂志

Endoplasmic reticulum stress(ERS)is closely related to the mechanisms of multiple diseases,and regulation of ERS has become a therapeutic target for several diseases.Previous studies by our group have demonstrated that ERS can be alleviated and neuronal cells can be protected by downregulating ERS-related proteins such as GRP78,caspase12 and caspase3.The research on ERS inhibitors has progressed rapidly in recent years,and they can be classified into various types such as molecular chaperones,small molecule compounds and natural products,such as 4-phenylbutyric acid(4-PBA),tauroursodeoxycholic acid(TUDCA)and tumor necrosis factor α-stimulating factor 6(TSG-6),etc.These inhibitors can regulate the ERS signaling pathway through different pathways,such as:silent information regulator 1(SIRT1)promotes the expression of anti-apop-totic proteins by inhibiting the PERK-eIF2α-ATF4-CHOP pathway,thus reducing apoptosis.In addition,SIRT1 deacetylates XBP-1,regulates the IRE1α-XBP1 signaling pathway,and inhibits the expressions of GRP78 and CHOP,thereby reducing the protein load of endoplasmic reticulum(ER)and alleviating ERS;PDE4 inhibitor regu-lates c-Jun-mediated apoptotic pathway,reduces the interaction between IRE1 and TRAF2,and attenuates the level of c-Jun phosphorylation,thereby restoring ER homeostasis.In addition,PDE4 inhibitor activates the antioxidant-acting Nrf-2 pathway,decreases the concen-tration of intracellular calcium ion and reduces the pro-duction of ROS;TSG-6 exerts anti-inflammatory effects by regulating the secretion of inflammatory factors through PERK-eIF-2α-NF-κB p65 and IRE1α-TRAF2-NF-κB p65 signaling pathways.In-depth exploration of the potential mechanism of action of ERS inhibitors is of great signifi-cance for finding ways to treat related diseases by regu-lating ERS.

Progress in adverse effects of sleep deprivation on body fertility / 中国药理学与毒理学杂志

Sleep is essential for the maintenance of human normal functions.Nowadays,the occurrence of active sleep deprivation(ASD)or passive sleep depriva-tion(PSD)is becoming more and more common due to the inability of the body adapting to the rapid changes in the internal and external environment.SD is not only an action,a brief process or a result,but also a directly or indirectly sustained state,which is associated to sleep time,circadian rhythm or sleep quality.SD can lead to numerous adverse effects on the body,such as sleep-related acute and chronic diseases.Long-term SD increases the risk of neurological and cardiovascular dis-eases as well as immune system dysfunction.In addi-tion,SD may affect the reproductive health of the body,giving rise to a series of potential fertility problems.In recent years,the correlation research and mechanism between SD and the related diseases have become a focus of scholars' attention.Numerous lines of evidence suggest that pathological sleep,such as insomnia and sleep apnea syndrome,is associated with impaired repro-ductive function.Disruptions in the circadian rhythm can also lead to impaired hypothalamic-pituitary-gonadal(HPG)axis function and thereby interfere with the repro-ductive process.Our research team has demonstrated that SD significantly affects the fertility of male and female rats and has adverse effects on reproduction.By new generation sequencing(NGS)and RT-PCR verifica-tion,we have identified differently expressed genes that are involved in mediating the effect of SD on fertility.However,the mechanisms and biological macromolecules regulated by SD are worthy of being further explored.This paper provides a brief review of SD research and then focuses on the adverse impact of SD on fertility,conducting a literature review to sort out the ideas and pro-vide references for research in this field.

The expression changes of lncRNA in patients with systemic lupus erythematosus and its correlation with regulatory T cells / 中华风湿病学杂志

Objective:To explore the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T cells (Tregs) by detecting the lncRNAs expression profiles in patients with systemic lupus erythematosus (SLE), then analyze the correlation between Tregs and lncRNAs and the clinical features of SLE patients. We also predict the mechanism by which lncRNAs regulate the differentiation and development of Tregs, and provid new approach for the treatment of SLE.Methods:Peripheral blood of 9 active SLE patients was collected and mononuclear cells (PBMCs) were extracted. The lncRNAs expression profiles of PBMCs was analyzed by whole transcriptome sequencing. Nine healthy people served as controls to screen the differentially expressed lncRNAs, and to analyze the correlation between lncRNAs and Tregs number. Pearson test was used to analyze the correlation between lncRNA and the number of Tregs, and the correlation between Treg-associated lncRNAs and systemic lupus erythematosus disease activity index(SLEDAI) score, erythrocyte sedimentation rate (ESR), C3, C4 in SLE patients. The targeted genes of Treg asso-ciated lncRNAs were predicted with miRcode and Targetscan databases and co-expression network.Results:There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs ( P<0.05) and 106 low expressed lncRNAs ( P<0.05). The expression of ANKRD44-AS1 ( r=0.74, P=0.022), LINC00200 ( r=0.70, P=0.037), AP001363.2 ( r=0.78, P=0.014) and LINC02824 (r=0.79, P=0.011) were positively correlated with the number of Tregs, and the expression of AP000640.1 ( r=-0.72, P=0.028), AC124248.1 ( r=-0.77, P=0.016), LINC00482 ( r=-0.83, P=0.005) and MIR503HG ( r=-0.96, P<0.001) were negatively correlated with the number of Tregs. Among these eight Tregs associated lncRNAs, the expression of LINC00482 ( r=-0.73, P<0.001) and MIR503HG ( r=-0.76, P<0.001) were negatively correlated with C3. LINC00200, ANKRD44-AS1 and AP000640.1 related to Tregs regulated the expression of STAT5, PLD1, HOPX and RUNX3 through competitively binding of miRNA or transregulatory mechanism, thereby regulating the differentiation and development of Tregs. Conclusion:The lncRNAs expression profiles are changed in SLE patients, the differentially expressed lncRNAs are associated with abnormal number and function of Tregs in SLE patients, and Treg associated lncRNAs are associated with SLE disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Tregs function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism.

The status of peripheral CD4 + T subsets in patients with rheumatism and their changes after immuno-modulatory combination therapies / 中华风湿病学杂志

Objective:To examinethe absolute numbers of cluster of differentiation (CD4) + T cell subsets in peripheral blood of patients with rheumatism and further to develop a new immunomodulatory therapies which aimed to restore their imbalanced CD4 + T lymphocyte subpopulation. Methods:A total of 6 395 rheumatic patients [4 430 females, 1 965 males, mean age (49±15) years] and 206 healthy controls (HCs) were enrolled in this retrospective cross-sectional study, which included rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), Psoriatic arthritis (PsA), systemic sclerosis (SSc), primary Sj?gren′s syndrome (pSS), Be?het's disease (BD), dermatomyositis/polymyositis (DM/PM), gout and vasculitis. Some patients received treatment combined with immunoregulatory drugs (IMiDs) such as low-dose interleukin (IL)-2, rapamycin, metformin, retinoic acid and coenzyme Q10. The absolute numbers of T helper cell (Th)1, Th2, Th17 and regulatory T cell (Treg) in peripheral blood (PB) of these individuals were measured by Flow Cytometery (FCM). Independent sample t test and paired sample t test were used to compare the levels of CD4 + T cell subsets in PB of patients and HCs, before and after treatment respectively, and P<0.05 was considered statistically significant. Results:Compared with HCs, the mean absolute number of Treg was significantly decreased [(31±15) cell/μl vs (27±17) cell/μl, t=3.407, P<0.01] and the ratio of Th17/Treg was increased in all patients [(0.3±0.2) vs ( 0.4±0.7), t=-9.508, P<0.01]. There was a significant increase in the number of Th17 in patients with AS [(10±8) cell/μl, t=-5.403, P<0.01], PsA[ (11±11) cell/μl, t=-3.829, P<0.01], SSc [(7±6) cell/μl, t=3.114, P<0.01], BD [(11±9) cell/μl), t=-4.774, P<0.01] and gout [(11±9) cell/μl, t= -4.604, P<0.01) , and we observed lower level of Treg in patients with RA[(28±15) cell/μl, t=3.032, P<0.01], SLE [(21±21) cell/μl, t=6.836, P<0.01], AS [(28±15) cell/μl, t=2.216, P<0.05], SSc [(27±16) cell/μl, t=3.698, P<0.05], BD [(27±17) cell/μl, t=2.502, P<0.05], DM/PM [(27±22) cell/μl, t=2.974, P<0.01) and gout [(28±15) cell/μl, t=2.079, P<0.05). After IMiDs combination treatment, the levels of CD4 + T subsets were increased. Interestingly, the expansion of Treg was much more dramatical than those of other effector T cells, resulting in a decrease in ratios of Th17/Treg, especially in SLE [(0.6±1.0) vs (0.5±0.4), t=3.157 , P<0.01]. Conclusion:Impaired balance of pro- and anti-inflammatory immune cells, especially insufficiency of Treg, might be a cornerstone of the pathogenesis of rheumatism. The new immunomodulatory therapies could relatively specifically promote Treg proliferation and restored patients' autoimmune tolerance, which isexpected to provide a new strategy for the treatment of rheumatism.

Study on the relationship between intestinal flora and peripheral blood cytokines in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective:To detect the characteristics of bacteria in the feces of patients with rheumatoid arthritis (RA) and to further discover the relationship between intestinal flora and the status of peripheral cytokine, which might be able to provide new ideas for clinical treatment.Methods:The bacterial diversity and abundance of 111 RA patients and 100 age-and gender-matched healthy controls (HC) were detected by 16S high-throughput sequencing platform and compared. Based on the 16S rDNA high-throughput sequencing platform, the 16S rDNA V3 region in the participants' fecal specimens were analyzed and compared to screen for different bacterial groups. Alpha diversity was analyzed by the mothur software and the screening for different flora was tested by using Mann-Whitney, and the relationship between intestinal flora and peripheral cytokines were analyzed, too.Results:There was no significant difference in gender ( χ2=0.005, P=0.947) and age ( t=0.728, P=0.467) between the two groups. Patients with RA had a lower chao1 index ( Z=-2.188, P=0.029) and ACE index ( Z=-2.078, P=0.038) of species richness, and the Shannon index ( Z=-2.064, P=0.039) and Simpion index ( Z=-2.064, P=0.039) of diversity index in the feces compared with those of HC. At the genus level, the relative abundance of Bifidobacterium ( Z=-2.388, P=0.017), Lactobacillus ( Z=-2.543, P=0.011), Clostridium sensu stricto ( Z=-3.842, P<0.01), Blautia ( Z=-2.064, P=0.039) , Clostridium Ⅺ ( Z=-2.682, P<0.01), Turicibacter ( Z=-2.437, P=0.015), Phascolarctobacterium ( Z=-3.524, P<0.01), Megasphaera ( Z=-2.87, P<0.01), Veillonella ( Z=-2.472, P=0.013), Citrobacter ( Z=-3.263, P<0.01) and Escherichia/Shigella ( Z=-4.265, P<0.01) in RA were significantly higher than those of HC ( P<0.05), Butyricimonas ( Z=-3.071, P=0.002), Odorbacter ( Z=-2.257, P=0.024), Blautia ( Z=-2.064, P=0.039), Clostridium_ⅩⅣb ( Z=-2.901, P<0.01), Lachnospiracea_incertae sedis ( Z=-2.159, P=0.031), Acetivibrio ( Z=-2.995, P<0.01), Butyricicoccus ( Z=-2.162, P=0.031) and Gemmiger ( Z=-2.949, P<0.01) relative abundance were significantly decreased in RA patients ( P<0.05). LEfSe analysis showed γ-proteobacteria and Lachnospiraceaehad the most significant difference between the two groups. Further, patients with high inflammatory cytokines such as IL-17 and TNF-α hada higher relative abundance of Prevotella. Conclusion:The diversity and abundance of intestinal flora in RA patients are significantly different from those of healthy population, which is closely related to the levels of inflammatory cytokines, suggesting imbalance of intestinal flora might be involved in the occurrence and development of RA.

Effects of sulforaphane on anxiety and fear memory in AD mice and its oxidative stress mechanism / 中华行为医学与脑科学杂志

Objective:To explore the effects of sulforaphane (SFN), an activator of Nrf2, on anxiety and fear memory in Alzheimer's disease(AD) model mice and mechanism.Methods:The AD mice and wild type (WT) mice with the same background were randomly divided into four groups ( n=12 for each group): wild type + normal saline group (WT+ NS), wild type + sulforaphane (WT+ SFN), AD model + normal saline group (AD+ NS) and AD model + sulforaphane group (AD+ SFN). SFN was dissolved in normal saline (0.9% NaCl) and prepared solution with concentration of 1 g/L.According to body weight, mice in WT+ SFN group and AD+ SFN group were intraperitoneally injected with SFN (10 mg/kg), and mice in WT+ NS group and AD+ NS group were intraperitoneally injected with the same volume of normal saline once a day for 30 days.The open field test was used to detect the autonomous exploration ability and anxious behavior of mice.The elevated cross maze was used to detect the anxiety of mice.Conditional fear test was used to test the fear memory behavior of mice.Finally, the expression of superoxide dismutase(SOD) and malondialdehyde(MDA) in the hippocampus and cerebral cortex were detected by ELISA.Two-way ANOVA analysis was performed using GraphPad Prism 8.0.2 software. Results:In the open field test, the percentage of time in central region in AD+ SFN group ((9.99+ 0.37)%) was higher than that of AD+ NS group ((8.47+ 0.42)%) ( q=3.842, P<0.05). In the elevated cross maze, the percentage of time in open arm of AD+ SFN group ((26.2±1.6)%) was higher than that in AD+ NS group ((15.8±1.0)%) ( q=7.452, P<0.01). In the conditional fear test, all the mice of the four groups developed the fear memory, but AD+ SFN group showed higher freezing time ratio ((64.5±3.8)%) than AD+ NS group ((51.0±4.3)%)( q=5.266, P<0.01) in the testing stage.After SFN intervention, the important indicator of oxidative stress, the expression levels of SOD in hippocampus ( q=6.370, P<0.01) and cortex ( q=7.858, P<0.01) of AD mice increased, while the level of MDA in hippocampus ( q=5.146, P<0.05) and cortex ( q=5.833, P<0.01) decreased. Conclusion:SFN may inhibit oxidative stress through Nrf2 pathway, thereby improving anxiety and fear memory in AD mice.

Correlation between the changes of regulatory T cells in peripheral blood and disease activity measures in rheumatoid arthritis / 中华风湿病学杂志

Objective:To investigate the level of regulatory T (Treg) cells of peripheral blood and evaluate the correlation between Treg cells and disease activity in rheumatoid arthritis (RA) to further clarify the role of Treg cells in the pathogenesis of RA.Methods:The participants included 300 patients with RA, from the Second Hospital of Shanxi Medical University between January 2016 and September 2018 and 100 gender and age matched healthy individuals. The absolute numbers and proportion of Treg cells and helper T (Th) 17 cells and the ratio of Th17/Treg in peripheral blood of these individuals were detected by flow cytometry combined with standard absolute counting beads. Main statistical analysis methods were t test, spearman correlation and rank sum test. Results:Patients with RA had lower absolute numbers [(35±13) cells/μl vs (26±17) cells/μl, t=4.815, P<0.01] and percentage [(5.1±1.5)% vs (4.4±2.0)%, t=4.111, P<0.01] of Treg cells compared with those in healthy controls, while the number ( t=1.114, P=0.266) and proportion ( t=1.577, P=0.116) of Th17 cells were not significantly changed. RA patients, regardless of new onset (no prior treatment) or treatment with immunosuppressants, had significantly lower absolute numbers of Treg cells [healthy controls (35±13) cells/μl; the Treg cells in new onset patients was (31±17) cells/μl, t=1.974, P=0.049; Treg cells in treated patients was (24±16) cells/μl, t=5.978, P<0.01] but not Th17 cells than healthy controls. With the increase of disease activity score uses 28 joint counts (DAS28), the absolute counts of peripheral Treg cells trended to decrease [remission group (33±15) cells/μl, low activity group (31±17) cells/μl, moderate activity group (28±17) cells/μl, high activity group (24±16) cells/μl], and were negatively correlated with DAS28( r=-0.139, P=0.016) and erythrocyte sedimentation rate (ESR) ( r=-0.116, P=0.046). Conclusion:The absolute counts of peripheral Treg cells decreased significantly, which are associated directly with the pathogenesis of RA rather than high-dose glucocorticoids or immunosuppressive agents. Changes in circulating Treg cells number may play a prominent role in the disease process of RA, which provides clinical basis for evaluation of disease activity and exploration of new effective therapies.

Effects of low-dose interleukin-2 on peripheral regulatory T cells counts of patients with psoriatic arthritis and its short-term clinical efficacy / 中华风湿病学杂志

Objective To study the expression of peripheral blood lymphocyte subsets in psoriatic arthritis (PsA) patients and the short-term efficacy of low doses of interleukin-2 (IL-2). Methods Ninety-five patients with PsA were enrolled as study subjects and 106 healthy people as control group. On the basis of conventional treatment, a total of 22 PsA patients were randomly selected and treated with low dose IL-2 (5 ×105 U/d, continuously used for 5 days, IH), and the disease condition and lymphocyte changes were observed. Flow cytometry was used to detect the absolute count of T subsets dominated by regulatory T cell(Treg) and T helper cell 17(Th17). Wilcoxon rank sum test, χ2 test and Spearman correlation analysis were used for statistical analysis. Results The absolute number of Th17 cells of PsA patients [7.2 (4.0, 12.8) cells/μl] was higher than that of the control group [5.9(4.0, 8.6) cells/μl] (Z=-1.997, P=0.046), the number of Treg cells [25 (17, 36) cells/μl] decreased compared with the control group [30 (23, 40) cells/μl] (Z=-2.957, Z=0.003), T/Treg [50 (36), 76)], B/Treg [7.6 (5.4, 11.5)], CD4+T/Treg [27 (21, 42)], CD8+T/Treg [20 (12, 30)], Th17/Treg [0.34(0.13, 0.51)], Th1/Treg [4.4(2.3, 7.2)], Th2/Treg [0.34(0.20, 0.53)], compared with control group T/Treg [40 (32, 54)], B/Treg [6.5 (4.2, 8.1)], CD4+T/Treg [20 (17, 25)], CD8+T/Treg [16 (11, 24)], Th17/Treg [0.19 (0.13, 0.31)], Th1/Treg [3.5 (1.8, 5.8)], Th2/Treg [0.24 (0.15, 0.39)] were significantly increased (Z=-3.365, -3.217,-5.285, -2.097, -1.69, -1.482, -2.304, P<0.05). Treg cells were negatively correlated with disease activity indexes TJC (r=-0.213, P=0.038), VAS (r=-0.299, P=0.003), PHGA (r=-0.287, P=0.005), DLQI (r=-0.208, P=0.043). Th17 cells increased from [6.3 (2.3, 11.5) cells/μl] to [11 (7, 20) cells/μl, Z=-2.808, P=0.005] after low-dose IL-2 treatment, Treg cells increased from [27 (15, 30) cells/μl] to [71 (37, 98) cells/μl, Z=-3.945, P<0.01]. Because the growth rate of Treg was much higher than Th17, Th17/Treg [before IL-2 treatment: 0.26 (0.11, 0.44), after IL-2 treatment: 0.14 (0.1, 0.35)] returned back to the normal range. After the treatment with IL-2, the patient's activity indicators were significantly improved, and there were no reversible adverse reactions. Conclusion The reduction of Treg cells may be involved in the occurrence and devel-opment of PsA. Low-dose IL-2 treatment can effectively promote the proliferation of Treg cells and the recovery of Th17/Treg balance, which is conducive to the improvement of the condition and good safety.

Reduction and significance of CD4+CD25+Foxp3+T regulatory cells in the peripheral blood of patients with common autoimmune diseases / 中华风湿病学杂志

Objective To determine the CD4+CD25+Foxp3+T regulatory (Treg) cell levels in peripheral blood (PB) of patients with autoimmune diseases (AID) and age-and sex-matched healthy controls. Methods Clinical data and laboratory examinations of AID cases (n=1561) and healthy controls (n=196) were enrolled. The levels of PB Treg cells, other T lymphocyte subsets [total T, CD4+T, CD8+T, T helper1 (Th1), T helper 2 (Th2), and T helper17(Th17) cells] and clinical indicators, laboratory test results were analyzed retro-spectively. Data were analyzed by t test, Mann-Whitney U test,χ2 test and Spearman correlation analysis. Results ①The absolute counts of Treg [22.9(18.31, 36.47) vs 30.24(21.85, 41.34), Z=-3.974, P<0.01], total T (Z=-4.234, P<0.01), CD8+T (Z=-3.801, P<0.01), Th17 (Z=-3.740, P<0.01) cells in PB of patients with AID were significantly lower than those of healthy controls, the levels of CD4+T/Treg (Z=-3.366, P=0.001), Th1/Treg (Z=-3.213, P=0.001) and Th2/Treg (Z=-2.490, P=0.013) in PB of AID patients were higher than those of healthy controls.② The levels of inflammatory indicators were associated with numbers of T lymphocyte subsets. ③ The levels of Treg (Z=-3.624, P<0.01), total T (Z=-2.954, P=0.009), CD4+T (Z=-3.005, P=0.003), Th2 (Z=-1.896, P=0.049) cells in PB of the patients who had been treated with hormones and/or biological or non-biological disease-modifying anti-rheumatic drugs (DMARDs) were significantly lower while the levels of total T/Treg (Z=-2.460, P=0.014), CD8+T/Treg (Z=-3.197, P=0.001) in PB were higher than those of the primary treatment patients. ④ The levels of Treg (Z=-7.105, P<0.01), total T (Z=-2.954, P<0.01), CD4+T (Z=-6.909, P<0.01), Th1 (Z=-4.875, P<0.01), Th2 (Z=-5.751, P<0.01), Th17 (Z=-5.121, P<0.01) cells in PB of the patients with important organs involvement were lower while the ratios of total T/Treg (Z=-4.500, P<0.01), CD8+T/Treg (Z=-5.925, P<0.01) were higher than those non-organ involvement patients. ⑤ The absolute counts levels of T lymphocyte subsets in the AID patients were not significantly correlated with whether there was a single AID and/or multiple AID overlaps. Conclusion The absolute number of peripheral Treg cells decreases significantly in AID, and is correlated with inflammatory indicators. Patients with retreated and organ involve-ment have fewer Treg cells. Our results suggest that Treg cells may play an important role in the pathogenesis of AID.

Changes and significance of CD5+B lymphocyte in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To measure the number of lymphocytes, B lymphocytes, CD5+B lymphocytes and level of IL-10 in peripheral blood of patients with systemic lupus erythematosus (SLE), and analyze their effects in the disease. Methods In this study, 84 cases of patients with SLE were randomly selected and evaluated according to the activity index (SLEDAI). These cases were divided into low activity group (SLEDAI0.05). In addition, the level of serum IL-10 in whether the low activity group (t=1.935, P=0.031) or the high activity group (t=3.048, P=0.012) was all higher than the normal control group. The level of serum IL-10 in patients with systemic lupus erythematosus was positively associated with SLEDAI score (r=0.425, P=0.024) and ESR (r=0.479, P=0.008), but was negatively correlated with complement 4 (r=-0.359, P=0.031). Conclusion The total number of lymphocytes in patients with SLE decreases significantly, while B lymphocytes increases significantly. The number of CD5+ B lymphocytes and the serum IL-10 level are also changed. It maybe related to the patient's inflammatory environment, and the number of CD5+B lymphocytes and the serum IL-10 level may be associated with disease activity.

Auxiliary reference significance of Blumensaat line for knee joint disease / 中国组织工程研究

BACKGROUND:With the development of sports medicine and research of radiologic imaging techniques, Blumensaat line (the radio-opaque line at the roof of the intercondylar notch) has been paid increasing attention. Blumensaat line is considered as measurement indexes of knee diseases. Taking advantage of the Blumensaat line, many surgeons and radiography physicians are trying to diagnose some knee diseases. OBJECTIVE:According to the knowledge about Blumensaat line in auxiliary diagnosis of knee disease, we hoped that it wil have a wide application in clinic. METHODS:A computer-based online search of CBM, CNKI, Wangfang Database and PubMed between 2000 and 2015 was performed for articles addressing Blumensaat line. We summarized its application as different diagnostic indicators. The key words were patel a alta, Blumensaat line, anterior cruciate ligament (ACL) injuries and ACL reconstruction. Thirty-nine studies were accorded with the inclusion criteria. RESULTS AND CONCLUSION:Blumensaat line represents the tangential y hit part of the roof in the intercondylar fossa. The line can be used for diagnosing ACL injuries and directing ACL restruction. (1) Blumensaat line and patel a alta:Patel a heights can be measured with the use of Blumensaat method, modified Blumensaat method and modified Blumensaat ratio. Modified Blumensaat ratio was found by Japanese researchers in 2014 and it is efficient. (2) Blumensaat line and ACL injuries:Blumensaat angle is formed by Blumensaat line and ACL. If this angle is negative or it is greater than 15°, we can draw a conclusion that the ACL was hurt. (3) Harner’s method can be used for choosing an accurate isometric point and a perfect bone tunnel’s angel in ACL reconstruction.