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In recent years， the incidence of colorectal cancer has been rising in China， and with the promotion of early screening and early diagnosis， most colorectal cancers are able to achieve long-term survival through timely diagnosis and treatment. Nevertheless， 30%-70% of patients with early to mid-stage colorectal cancer after radical surgery still have psychological problems such as anxiety， depression， and fear of recurrence and metastasis， and they hope to seek help from traditional Chinese medicine（TCM） treatment. In order to further standardize the integrated traditional Chinese and western medicine psychological rehabilitation interventions of stage Ⅰ-Ⅲ colorectal cancer after radical surgery， and to improve the diagnosis and treatment level， under the support of the pilot project of clinical collaboration between Chinese and western medicine for major and difficult diseases of National Administration of TCM， experts in oncology， integrated Chinese and western medicine， psychology， surgery， nursing， evidence-based medicine and other disciplines from 10 units nationwide participated in the work， led by Xiyuan Hospital，China Academy of Chinese Medical Sciences and Beijing Cancer Hospital. Based on the methodology and process of guideline development of the World Health Organization Handbook for Guideline Development and the Regulations for Group Standards of China Association of Chinese Medicine， the Guidelines for Psychological Rehabilitation Intervention Combined Integrated Traditional Chinese and Western Medicine After Radical Surgery for Early and Middle Stage Colorectal Cancer have been developed according to the current best evidence， extensive consultation with clinical experts and following the situation of current clinical practice. The guideline provides the psychological characteristics， the needs and willingness to accept psychological rehabilitation， the interventions for psychological rehabilitation， evaluation of efficacy， follow-up review， educational guidance and others of patients with stage Ⅰ-Ⅲ colorectal cancer after radical surgery. It can provide guidance for TCM（integrated Chinese and western medicine） clinicians and psychologists engaged in the psychological rehabilitation of integrated Chinese and western medicine oncology， especially for doctors in primary medical institutions.
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Objective:To investigate the clinical significance of the transforming growth factor-β receptor I (TGF-βRⅠ) expression in na?ve CD4 + T cells from patients with systemic lupus erythematosus (SLE). Methods:Na?ve CD4 + T cells were purified using magnetic microbeads from peripheral blood mononuclear cells of SLE patients and healthy controls. Real-time quantitative PCR was used to detect TGF-βRⅠ mRNA level, and flow cytometry was used to detect the percentage of CD69 +CD4 + T cells. Data were analyzed by t test and Pearson correlation analysis. Results:The level of TGF-βR Ⅰ mRNA in na?ve CD4 + T cells from SLE patients was significantly lower than that in healthy controls [(0.674±0.873) vs (1.445±1.112), t=2.301, P<0.05]. The TGF-βR Ⅰ mRNA level was negatively correlated with systemic lupus erythematosus disease activity index (SLEDAI) ( r=-0.376, P<0.05), erythrocyte sedimentation rate (ESR) ( r=-0.376, P<0.05), serum creatinine ( r=-0.323, P<0.05) and 24 h urine protein ( r=-0.331, P<0.05), and positively correlated with serum com-plement C3 ( r=0.528, P<0.01). The level of TGF-βRⅠ mRNA level in na?ve CD4 + T cells in SLE patients with renal involvement was lower than that in SLE patients without renal involvement [(0.525±0.536) vs (1.071±1.007), t=2.198, P<0.05]. The TGF-βR Ⅰ mRNA level in the na?ve CD4 + T cells in anti-dsDNA antibody positive group was lower than that in the anti-dsDNA antibody negative group [(0.344±0.315) vs (0.958±1.076), t=2.277, P<0.05]. The expression of TGF-βRⅠ mRNA in na?ve CD4 + T cells from SLE patients was reduced after 24 h stimulation with anti-CD3/CD28 beads [(0.047±0.013) vs (1.008±0.129), t=14.38, P<0.01], which was partially reversed by dexamethasone treatment [(0.240±0.042) vs (0.047±0.013), t=7.845, P<0.01]. Meanwhile, dexamethasone significantly decreased the expression of CD69 in CD4 + T cells [(15.0±2.1)% vs(34.9±2.0)%, t=32.57, P<0.01]. Conclusion:The abnormally low expression of TGF-βRⅠ in na?ve CD4 + T cells may be involved in the pathogenesis of SLE. Glucocorticoid treatment can upregulate the expression of TGF-βRI and inhibit the activation of T cells, This suggests suggesting that TGF-βRⅠ may be a potential target for SLE treatment.
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Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.
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Objective@#To investigate the expression of transcription factor AT-rich interaction domain 3a (ARID3a) in peripheral blood B cells of patients with systemic lupus erythematosus (SLE) and its clinical significance.@*Methods@#Peripheral blood mononuclear cells were isolated from 17 SLE patients and 13 healthy controls. Then, the expression of ARID3a by B cells was determined by flow cytometry. Data was analyzed with independent sample t test. The correlations between the frequencies of ARID3a+ B cells and clinical indicators of SLE patients were assessed by Pearson cor relation analysis. The expression of ARID3a in kidney was detected by immunohistochemistry in 14 cases of lupus nephritis (LN).@*Results@#The percentages of ARID3a+ B cells in SLE patients [(51.6±3.2)%] were significantly higher than those in healthy controls [(32.6±3.4)%](t=4.0, P<0.01). There was a positive correlation between the percentages of ARID3a+ B cells in SLE patients and their 24-hour urinary protein (r=0.68, P<0.05). Furthermore, the percentages of ARID3a+ B cells in peripheral blood from patients with active LN[(62.3±4.3)%] were remarkably higher than that from patients without LN or with inactive LN [(43.3±2.8)%] (t=3.8, P<0.01). The expression of ARID3a in glomerula and tubules of LN patients markedly increased.@*Conclusion@#Elevated expression of transcription factor ARID3a in B cells may participate in the pathogenesis of LN.
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Objective@#To explore the plasma level change of soluble tumor necrosis factor related apoptosis inducing ligand (sTRAIL) in patients with systemic lupus erythematosus (SLE) and its clinical significance.@*Methods@#Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expressions of TRAIL and TRAIL receptors-1 (TRAIL-R1) and TRAIL-R2 in the peripheral blood mononuclear cells (PBMCs) derived from active SLE patients (n=26) and healthy controls. Enzyme linked immuno sorbent assay (ELISA) was used to detect the plasma level of sTRAIL in the active SLE patients (n=42), healthy controls (n=21). Pearson correlation analysis was used to analyze the correlation of sTRAIL with clinical and laboratory parameters.@*Results@#The plasma levels of sTRAIL [(82±5) pg/ml] in SLE were significantly higher than that in healthy controls [(49±3) pg/ml], the difference was statistically significant (t=4.10, P<0.01). The plasma levels of sTRAIL in SLE with inactive disease [(92±14) pg/ml], mild active disease [(80±9) pg/ml], moderate active disease [(74±12) pg/ml] and severe active disease [(83±8) pg/ml] were higher than healthy controls, the difference was statistically significant (H=18.07, P<0.01). The mRNA levels of TRAIL and TRAIL-R2 in PBMCs derived from SLE patients were significantly higher than those in healthy controls [(1.04±0.08) vs (1.80±0.25), t=2.10, P<0.05 and (1.07±0.12) vs (2.08±0.21), t=3.27, P<0.01]. In SLE with moderate and severe active disease, plasma sTRAIL levels were associated with the 24 hours urine protein.@*Conclusion@#Plasma sTRAIL may be predictors of SLE disease activity and TRAIL pathway may be a new potential target of SLE treatment.
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Objective To explore the clinical characteristics and prognostic indicators that classify patients with systemic lupus erythematosus (SLE) at risk of in-hospital mortality.Methods Medical records of 1611 SLE patients admitted between 1999-2009 were collected from 26 centers across Jiangsu province,and patients were divided into two groups based on the outcomes.The suspected risk factors of poor outcomes were selected and then analyzed by chi-square test,independent-samples t test,Wilcoxon rank sum test and Logistic regression.Results Among the 1 611 enrolled patients,91 patients were in the death group (5.6％) and 1 520 patients in the control group (94.4％).The duration of disease [28(4,60) m vs 12(2,47) m,Z=-3.290,P＜0.05),the rate of male/female (13.2％ vs 7.1％,x2=4.606,P＜0.05),as well as the occurrence rateof seizure (8.8％ vs 1.7％,x2=17.550,P＜0.05),psychosis (41.8％ vs 23.8％,x2=14.809,P＜0.05),lupus headache (19.8％ vs 6.0％,x22=-25.898,P＜0.05),alopecia (47.3％ vs 30.3％,x2=11.541,P＜0.05),pericarditis (35.2％ vs 22.0％,x2=8.408,P＜0.05),myocarditis (4.4％ vs 1.0％,x2=5.885,P＜0.05),fever (55.0％ vs 28.5％,x2=28.632,P＜0.05),decreased hemoglobin levels (60.9％ vs 44.8％,x2=8.603,P＜0.05),urinary casts (24.2％ vs 12.2％,x2=10.884,P＜0.05),hematuria (51.7％ vs 37.8％,x2=6.988,P＜0.05),decreased estimate glomerular filtration rate (eGFR)levels (27.6％ vs 11.0％,x2=18.12,P＜0.05),and elevated glutamic-oxaloacetic transaminase (AST) levels (30.2％ vs 17.9％,x2=8.176,P＜0.05) were higher in the death group.The frequency of arthritis (34.3％ vs 18.7％,x2=9.459,P＜0.05),proteinuria (31.6％ vs 14.3％,x2=12.169,P＜0.05),elevated erythrocyte sedimentation rate (ESR) levels (80.4％ vs 71.8％,x2=4.192,P＜0.05),decreased complement levels (44.2％ vs 17.6％,x2=24.881,P＜0.05) and anti-dsDNA antibodies positivity rate (39.7％ vs 23.1％,x2=9.963,P＜0.05) were higher in the control group.Logistic regression analysis showed seizure [OR =4.035,95％ CI(1.338,12.164),P＜0.05],lupus headache [OR=3.026,95％CI (1.406,6.511),P＜0.05],decreased hemoglobin (Hb) levels [OR =2.116,95％ CI(1.139,3.934),P＜0.05],decreased eGFR levels [OR =2.159,95％ CI(1.0 11,4.610),P＜0.05] and fever [OR=2.567,95％CI (1.422,4.634),P＜0.05] were positively correlated with in-hospital mortality,with elevated ESR levels [OR=0.418,95％CI (0.218,0.802),P＜0.05] and decreased complement levels [OR=0.328,95％CI (0.120,0.894),P＜0.05] negatively correlated (P＜0.05).Conclusion The results sugest that seizure,lupus headache,decreased Hb levels,decreased eGFR levels and fever are the most important predictors of in-hospital mortality.Clinicians should pay more attention to these symptoms in admission.
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Objective To evaluate the effect of cyclophosphamide (CTX) on the prognosis of different types of systemic lupus erythematosus (SLE).Methods A retrospective cohort study,in which 1 372 lupus patients were included,was conduted in 26 hospitals in Jiangsu province from 1999 to 2009.The data was analyzed by the chi-square test,Mann-Whitney U test,Kaplan-Meier survival analysis and Cox regression analysis.Results 1 372 SLE patients were followed up,in which 582 patients (42.4％) were treated with cycloph-osphamide and 790 patients (57.6％) were not.There were statistically significant differences in SLE disease activity index (SLEDAI) at admission and discharge between the two groups (t=3.398,P=0.001;t=5.044,P＜0.01).The survival rate was significantly higher in CTX treatment group compared to those without CTX administration (x2=4.667,P=0.031).Female (P=0.018,HR=0.68),disease duration ≤7 years (P=0.033,R=0.697),decreased levels of complement C3 (P=0.047,HR=0.7),and patients treated with cyclophosphamide and glucocorti-costeroid (P=0.047,HR=0.734) were predictors for good prognosis for CTX treatment.In patients with central nervous system (x2=6.611,P=0.010),heart and lung (x2=7.223,P=0.007) and renal system involvement (x2=5.217,P=0.022),there were statistically significant differences in survival rate and survival time between the CTX treated group and untreated group.Conclusion Cyclophosphamide treatment was beneficial for female SLE patients with low complement,short disease duration and important organ involvement such as heart,lung,kidney and central nervous system.
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Objective To explore the plasma level change of soluble tumor necrosis factor related apoptosis inducing ligand (sTRAIL) in patients with systemic lupus erythematosus (SLE) and its clinical significance.Methods Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expressions of TRAIL and TRAIL receptors-1 (TRAIL-R1) and TRAIL-R2 in the peripheral blood mononuclear cells (PBMCs) derived from active SLE patients (n =26) and healthy controls.Enzyme linked immuno sorbent assay (ELISA) was used to detect the plasma level of sTRAIL in the active SLE patients (n=42),healthy controls (n=21).Pearson correlation analysis was used to analyze the correlation of sTRAIL with clinical and laboratory parameters.Results The plasma levels of sTRAIL [(82±5) pg/ml] in SLE were significantly higher than that in healthy controls [(49 ±3) pg/ml],the difference was statistically significant (t=4.10,P＜0.01).The plasma levels of sTRAIL in SLE with inactive disease [(92±14) pg/ml],mild active disease [(80±9) pg/ml],moderate active disease [(74±12) pg/ml] and severe active disease [(83±8) pg/ml] were higher than healthy controls,the difference was statistically significant (H=18.07,P＜0.01).The mRNA levels of TRAIL and TRAIL-R2 in PBMCs derived from SLE patients were significantly higher than those in healthy controls [(1.04±0.08) vs (1.80±0.25),t=2.10,P＜0.05 and (1.07±0.12) vs (2.08±0.21),t=3.27,P＜0.01].In SLE with moderate and severe active disease,plasma sTRAIL levels were associated with the 24 hours urine protein.Conclusion Plasma sTRAIL may be predictors of SLE disease activity and TRAIL pathway may be a new potential target of SLE treatment.
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Objective To investigate the regulation of mesenchymal stem cells (MSCs) on the expression of tumor necrosis factor-α-induced protein 8-like 2 (TNFAIP8L2, TIPE2) in the peripheral blood-derived macrophages of systemic lupus erythematosus (SLE) patients. Methods The expression of TIPE2 mRNA in peripheral blood mononuclear cells (PBMCs) and macrophages from SLE patients were detected by Quantitative polymerase chain reaction (qPCR). The TIPE2 protein levels in SLE PBMCs and peripheral blood-derived macrophages were detected by western blot, flow cytometry and immunofluorescence staining, respec-tively. Data were analyzed by t test and Spearman correlation analysis. Results The TIPE2 mRNA expres-sion in PBMCs of SLE patients was significantly lower than that of healthy controls [(0.41 ±0.14) vs (1.06±0.39), t=5.376, P<0.01], as well as the TIPE2 protein level [(0.40 ±0.21) vs (1.09 ±0.26), t=2.963, P<0.05]. The expression of TIPE2 mRNA in peripheral blood-derived macrophages from SLE patients was significantly decreased [(0.56±0.24) vs (1.07±0.38), t=5.203, P<0.01). Moreover, TIPE2 mRNA level of peripheral blood-derived macrophages was negatively correlated with systemic lupus erythematosus disease activity index (SLEDAI) score (r=-0.60, P<0.01), 24-hour urinary protein (r=-0.46, P<0.05) and erythrocyte sedimentation rate (r=-0.46, P<0.05) in SLE patients. The percentage of TIPE2+cells in peripheral blood-derived macrophages (TIPE2+/CD14+)％ from SLE patients was significantly lower than that in healthy controls [(51.4 ±18.5)％ vs (82.4 ±7.5)％, t=2.679, P<0.05]. After 24 hours co-cultured with MSCs, the TIPE2 mRNA expression in SLE per-ipheral blood-derived macrophages was significantly increased [(2.2 ±0.7) vs (1.0 ±0.3), t=3.729, P<0.05). Immunofluorescence results showed the same increase of TIPE2 protein in SLE peripheral blood-derived macrophages [(0.112 ±0.020) vs (0.074 ±0.016), t=3.268, P<0.05]. Conclusion The TIPE2 level in peripheral blood-derived macrophages of SLE patients are decreased. MSCs upregulate the TIPE2 expression in vitro, suggesting that TIPE2 can be a new target for MSCs in the treatment of SLE.
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Objective To investigate the association of human leucocyte antigen (HLA-DRB1) with anti-melanoma differentiation-associated gene 5 (MDA5) expression in polymyositis/dermatomyositis (PM/DM).Methods Seventy patients with PM,104 patients with DM and 400 healthy controls were included.Genotyping of HLA-DRB1 was performed using the sequencing-based typing method.Levels of anti-MDA5 were measued by enzyme linked immunosorbent assay using recombinant MDA5 antigen.The frequencies of HLA-DRB1 alleles were compared between the patients and controls using a chi-square test or Fisher's exact test.Results Frequencies of DRB1 * 04∶01 [17.0％ vs 1.3％,corrected P-value (Pc)=3.8×10-8;odds ratio (OR)=16.2;95％ confidence interval (CI) (6.6,39.7)] and DRB1 * 12∶02 [(42.6％ vs 19.3％,Pc=0.008;OR=3.1;95％ CI(1.7,5.7)] were significantly higher in anti-MDA5 positive PM/DM patients compared with the controls.The frequencies of DRB1 * 04∶01 [P=5.2×10-6,OR=17.1,95％CI:(5.3,54.9)\ and * 12∶02 [P=3.8×10-4,OR=3.1,95％CI(1.7,5.7)] in anti-MDA5 positive DM-interstitial lung disease (ILD) patients were higher than those in the controls,whereas the frequencies of DRB1 * 04∶01 and * 12∶02 did not differ between the anti-MDA5 negative DM-ILD patients and the controls.No difference in the frequency of DRB1 alleles,other than * 04∶01,carrying the shared epitope (SE),i.e.* 01∶01,* 01∶02,* 04∶05 and * 10∶01,was observed between the controls and DM patients stratified by the presence of anti-MDA5 and ILD.Conclusion DRB1 * 04∶01 and * 12∶02 confer susceptibility to anti-MDA5 antibody production in DM,which cannot be explained by the SE hypothesis.
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Objective To explore the effects of leptin on the senescence of bone marrow-derived mesenchymal stem cells,frequencies of Treg and Th17 cells,and lupus disease in MRL/lpr mice,and to explore the pathogenesis of systemic lupus erythematosus (SLE).Methods Leptin (1 μg/g) or phosphate buffer saline (PBS) was injected into C57BL/6 (B6) mice,ob/ob mice and MRL/lpr mice intra-peritoneally.Urine protein was examined by Coomassie brilliant blue method.The levels of serum leptin,antinuclear antibody (ANA),anti-dsDNA antibody and immunoglobulin (Ig)G were detected by enzyme linked immunosorbent assay (ELISA).Bone marrow derived mesenchymal stem cells (MSCs) were isolated,and treated with or without leptin,then the senescence of MSCs were evaluated by SA-β-gal staining,the levels of p53 and p21 mRNA were measured by real time polymerase chain reaction (PCR),the protein levels of p53 and p21 were tested by Westem blotting method.Data were analyzed with t test and ANOVA.Results The level of serum leptin was higher in MRL/lpr mice than that of B6 mice [(4.5±0.8) ng/ml vs (2.3±0.5) ng/ml,t=2.38,P＜0.05].Leptin treatment in vivo accelerated the senescence of bone marrow-derived MSCs from all B6 mice,lupus mice and ob/ob mice,manifestedas increased frequencies of SA-β-gal positive cells [(20.6±0.6)％ vs (15.4±1.6)％,t=8.09,P＜0.05],higher levels of mRNA and p53 and p21 protein.Leptin treatment in vivo also down-regulated the frequency of Treg cells [(2.77±0.23)％ vs (5.01±0.18)％ t=3.91,P＜0.01],and up-regulated Th17 cells [(2.24± 0.11)％ vs (1.74±0.07)％,t=5.013,P＜0.01].The titer of ANA was further increased in leptin-treated MRL/lpr mice [(288±69) U/ml vs (190±90) U/ml,t=2.84,P＜0.05].The levels of serum anti-dsDNA antibody were also remarkably elevated [(12 399±1 237) U/ml vs (6 217±1 304) U/ml,t=3.44,P＜0.01].Leptin could increase the secretion of total IgG [MRL/Ipr (27.2±2.9) mg/ml vs (25.0±3.3) mg/ml,t=3.07,P＜0.05].The proteinuria concentration was increased in lupus mice [(1.00±0.10) mg/ml vs (0.81 ±0.06) mg/ml,t=3.31,P＜0.05],demonstrating that leptin accelerates lupus nephritis.Conclusion Leptin administr-ation in vivo enhances the senescence of bone marrow derived MSCs,dys-regulate of Treg/Th17 cells from MRL/Ipr mice,which impaires the role of immuno-modulation,and aggravates the progress of lupus disease.
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Objective To analyze the clinical profile of primary Sj(o)gren's syndrome (pSS) patientswith central nervous system (CNS) involvement.Methods Thirty-eight pSS-CNS patients at Nanjing Drum Tower Hospital between 2012 and 2016 were enrolled.These patients were divided into high activity group and moderate activity group,according to European League against Rheumatism Sj(o)gren's syndrome Disease Activity Index (ESSDAI).The imaging characteristics,clinical features,laboratory examinations and treatment of 38 cases were retrospectively analyzed.Quantitative differences were analyzed by the student's t-test and qualitative data were analyzed with chi-square or Fisher's exact test.Results The prevalence of central nervous system involvement in pSS patients was 2.93％(38/1 296),while 32％(12/38) as the initial symptom of pSS.Recurrence rate was 39％(15/38).Limb weakness,speech difficulty,sensory disorders,blurred visionwere the most frequent symptoms in pSS-CNS.Multiple lesions in Magnetic resonance imaging (MRI) examination and cerebrospinal fluid abnormality were seen in 94％ (15/16) pSS-CNS patients,among which intra-thecal IgG level increased in 50％ (8/16).In addition,the frequencies of lung involvement,immune associated thrombocytopenia,high-titer antinuclear antibody (ANA) were significantly higher in high activity group of pSS-CNS than those of moderate activity group.The value of above items was 4.7,5.0 and 5.3,respectively,and all the differences were significant (P＜0.05).After high-dose corticosteroids and immunosuppressive therapy,61％ (23/38) patient improved,37％(14/38) were unresponsive to treatment,and 3％(1/38) died because of acute massive cerebral infarction.For those unresponsive patients,mesenchymal stem cell transplantation or immune adsorption treatment might be effective.Conclusion The clinical manifestations of central nervous system are diverse,may be the initial presentations in some pSS patients,with low morbidity and high recurrence rate.Image and lumbar puncture are important for diagnosis.Pulmonary involvement,immune thrombocyto-penia,and high-titer ANA are frequently associated with the activity of pSS-CNS.Most patients have good response to the treatment regimens of high-dose corticosteroids and immunosuppressive therapy,mesenchymal stem cell transplantation or immuno-sorption therapy may be considered in those unresponsive cases.
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Objective To investigate the immune regulatory effects of umbilical cord mesenchymal stem cells (UC-MSCs) transplantation on CD4+LAP+Treg cells in the peripheral blood of patients with systemic lupus erythematosus (SLE).Methods CD4+LAP+ Treg cells were detected in the peripheral blood from 30 SLE patients and 30 normal controls by flow cytometry.Five SLE patients received UC-MSCs transplantation,and their peripheral blood was collected before and after 24 hours of cell infusion.The percentages of CD4+ LAP+ T cells were detected by flow cytometry.Data were analyzed with t test and Spearman correlation test.Results The percentage of CD4+LAP+ Treg cells in the peripheral blood of SLE patients [(2.49 ±0.23)％]decreased remarkably compared with healthy controls [(3.35±0.19)％] (r=3.079,P＜0.01),and it was negatively correlated with serum alanine aminotransferase (ALT) [(40±44) U/L,r=-0.51,P＜0.05],AST [(35±53) U/L,r=-0.52,P＜0.05) and ALP [(64±25) U/L,r=-0.53,P＜0.01) level res-pectively.24 hours after UC-MSCs transplantation,the percentages of CD4+LAP+ Treg cells increased signif-icantly in SLE patients[(3.6±0.9)％ vs (2.1±0.6)％,r=3.508,P＜0.05].Conclusion The significantly decreased percentage of CD4+LAP+ Treg cells in patients with SLE suggests thatthey may participate in the pathogenesis of SLE.UC-MSCs transplantation can upregulate the expression of CD4+LAP+Treg cells in SLE patients,and the modulatory effects of UC-MSCs on CD4+LAP+ Treg cells may be one of the mechanisms of UC-MSCs therapy in ameliorating the disease.
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Objective To investigate the abnormality of intrahepatic biliary epithelial cells autophagy in primary biliary cirrhosis (PBC) mice,and explore the mechanism of UC-Mesenchymal stem cell (MSCs) in treating PBC.Methods After establishing the PBC model,we divided them into the PBC model group;the UC-MSCs treatment group and the Stattic group [Signal transducer and activator of transcription 3 (STAT3) inhibitor group].Six mice were used as the control group.Liver pathology and the serum pyruvate dehydrogenase complex E2 subunit (PDC-E2) antibody titers were detected.Autophagosome of the intrahepatic biliary epithelial cell was observed by electronic microscope.Protein levels of STAT3/pSTAT3,Beclin-1 were detected by western blot.We cultured human intrahepatic biliary epithelial cells in vitro,and down regulated STAT3.After stimulated by GCDC,we co-cultured them with UC-MSCs,and collected the cells in order to detect LC3 Ⅱ.The measurement data were compared with t test or single factor analysis of variance.Results Compared with the control group,periportal inflammatory cell infiltration and granuloma formation were observed in the PBC group.MSCs treatment decreased the infiltration of inflammatory cells.The level of antiPDC-E2 of the PBC group (107±18) ng/ml was higher than that of the control group (42±6) ng/ml (q=6.326,P＜0.01),MSCs treatment down regulated anti-PDC-E2 level (43±4) ng/ml (q=5.801,P＜0.01).More autophagosomes in the PBC group (5.00±1.29) than the control group (1.75±0.25) were observed (q=4.061,P＞0.05).Western blot showed that the level of Beclin-1 was higher in PBC group (1.80±0.36) than the control group (0.40±0.20) (q =6.757,P＜0.01),MSCs reduced the expression of Beclin-1 (0.86±0.06)(q=4.536,P＜0.05) as well as Stattic (0.72±0.03) (q=5.226,P＜0.05).PBC group had a higher expression level of STAT3 (1.80±0.42) (q=5.730,P＜0.05) and pSTAT3 (2.04±0.29)(q=6.492,P＜0.01) than the control group (0.50±0.05)(0.91±0.14).MSCs treatment decreased the expression of STAT3 (0.51±0.13)(q =5.703,P＜0.01) and pSTAT3 (0.76±0.07) (q =7.388,P＜0.01) in intrahepatic biliary epithelial cells.After down regulated STAT3 of HiBECs,MSCs reduced the expression of LC3 Ⅱ of HiBECs.Conclusion The intrahepatic biliary epithelial cells autophage of PBC mice is abnormal,MSCs can alleviate PBC by down regulating the autophage of intrahepatic biliary epithelial cells via STAT3.
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Objective To explore the associations between interferon induced helicase C domain 1 (IFIH1) gene single nucleotide polymorphism (SNP) rs1990760 C >T and polymyositis/dermatomyositis (PM/DM) in Chinese Han patients from Jiangsu area. Methods A total of 183 PM/DM patients and 400 healthy controls were included. SNP typing was performed by Taqman MGB probe method. The distributions of genotypes and alleles and Hardy-Weinberg equilibrium (HWE) were examined by χ2 tests or Fisherˊs exact tests. Results The distribution of IFIH1 rs1990760 genotypes of all patients group and the control group were consistent with HWE. The frequencies of T and C alleles were not significantly different between the PM/DM group (20.8% and 79.2%, respectively), the DM group (20.9% and 79.1%, respectively), the PM group (20.5%and 79.5%, respectively) and control group (18.0%and 82.0%, respectively). In recessive model (TT vs CT+CC) and additive model (TT vs CC), the frequencies of TT genotype in PM/DM group (6.6% vs 2.8%; χ2=4.8 and 4.54, respectively; both P=0.03) and in DM with interstitial lung disease (ILD) group (8.3% vs 2.8%;χ2=4.84 and 4.41, respectively; P=0.03 and 0.04, respectively) were significantly higher than those in the control group.In recessive model (TT vs CT+CC), the frequency of TT genotype in PM without ILD group was significantly higher than that in the control group (9.8% vs 2.8%, χ2=5.56, P=0.04). The genotype and allele distributions of rs1990760 were not significantly different between the anti-MDA5 positive group and control group. Conclusion The rs1990760 TT genotype of IFIH1 gene may be associated with the susceptibility of PM/DM in Jiangsu Han Chinese population, and the associations may differ based on the ILD status.
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Objective The purpose of this study is to observe the changes of immune cell subsets in lupus mice after umbilical cord mesenchymal stem cells (UC-MSCs) transplantation. Methods B6.MRL-Faslpr lupus mice were randomly divided into the following three groups: the UC-MSCs treated group, the fibroblast like synoviocytes (FLS) treated group and the untreated group. MSC (1×106) or FLS (1×106) were injected into the tail vein of lupus mice respectively. Four weeks after treatment, the spleen index was calculated. The pathological changes of kidney were assessed by HE staining. The frequencies of immune cell subsets in spleen and macrophage in kidney as well as abdominal cavity were analyzed by flow cytometry. Data were analyzed with t test. Results The spleen index of UC-MSCs treated lupus mice [(79 ±9) mg/10 g] and IgG level [(7.5±1.5) mg/ml] were significantly decreased when compared with FLS treated group [(147±23) mg/10 g, t=2.78, P<0.01] [(17.0 ±2.8) mg/ml, t=3.00, P<0.01] and the untreated group [(156 ±16) mg/10 g, t=4.29, P<0.01] [(16.7 ±1.6) mg/ml,t=4.01, P<0.01]. HE staining also showed that the pathological changes of kidney were alleviated after MSCs transplantation. In addition, the frequency of plasma cells in the untreated group [(2.61 2± 0.318)% vs (0.306±0.017)%, t=7.22, P<0.01] and the FLS treated group [(2.412±0.297)% vs (0.306±0.017)%, t=7.07, P<0.01] were markedly higher than MSCs treatment [(0.306 ±0.017)%]. Moreover, the frequency of CD25+Foxp3+/CD4+Treg in the MSCs treated group [(15.08±0.81)%] was significantly increased compared with the untreated group [(8.02 ±0.47)%, t=7.45, P<0.01] and FLS treated group [(8.80 ±0.23)%, t=7.39, P<0.01]. MSCs treatment resulted in a decrease in CXCR5+PD1+/CD4+Tfh and IFNγ+/CD4+Th1 subset, compared with the untreated group [(14.3±1.5)%vs (31.5±3.3)%, t=5.25, P<0.01] [(1.78±0.27)% vs (5.93±1.56)%, t=2.60, P<0.05] and the FLS treated group [(14.3±1.5)%vs (28.8±2.2)%, t=5.49, P<0.01] [(1.78±0.27)%vs (4.88±0.81)%, t=3.61, P<0.01]. The frequency of macrophage in kidney of the MSCs treated group [(3.52 ±0.37)%] was markedly increased compared with the untreated group[(1.58±0.29)%, t=3.25, P<0.01], while neither the IL4+/CD4+Th2 subset nor the IL17+/CD4+Th17subset and the frequency of macrophage in abdominal cavity showed significant changes in the three groups. Conclusion These findings suggest that the therapeutic effects of MSCs on lupus mice may mediate through increasing the frequency of spleen Treg and renal macrophage and decreasing the frequency of Tfh, Th1 and plasma cells.
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Objective To investigate the effects of artesunate (ART) on interstitial pneumonia and sialadenitis in MRL/lpr mice.Methods A total of 18 MRL/lpr mice were randomly allocated to a hydroxychloroquine sulfate (HCQ) group,a ART group and a control group.At the age of 18 weeks,the mice in the HCQ group and ART group were given HCQ 150 mg/kg daily and ART 50 mg/kg daily for 12 weeks,respectively.The histopathological changes of pneumonitis and submaxillaritis were assessed by hematoxylin and eosin staining.The levels of monocyte chemoattractant protein-1 (MCP-1) in the serum and urine were measured by the enzyme-linked immunosorbent assay.Results At the age of 30 weeks,the index of peribronchiolar lesion (1.62 ± 0.19,1.52 ± 0.30 vs.1.95 ± 0.34;all P＜0.05),the index of perivascular lesion (1.23 ± 0.18,1.28 ± 0.12 vs.1.57 ± 0.33;all P＜0.05),the alveolar lesions index (1.35 ± 0.16,1.05 ± 0.15 vs.1.72 ± 0.34;all P＜0.05) and the submaxillaritis index (1.48 ± 0.22,1.43 ± 0.15 vs.1.84 ± 0.34;all P＜0.05) in the HCQ group and the ART group were significantly decreased than those in the control group.The MCP-1 levels in the serum (1 103.02 ± 185.56 pg/ml,1 072.37 ± 242.43 pg/ml vs.1 490.67 ± 329.43 pg/ml;all P＜0.05) and urine (189.16 ± 70.85 pg/ml,198.79 ± 113.47 pg/ml vs.446.79 ± 192.31 pg/ml;all P＜0.05) in the HCQ group and the ART group were significantly lower than those in the control group.Conclusion ART can decrease the MCP-1 level,and ameliorate interstitial pneumonitis and sialadenitis in MRL/lpr mice.
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ObjectiveTo systematically evaluate the association between smoking and the risk of primary biliary cirrhosis (PBC) from the perspective of evidence-based medicine. MethodsA literature search was performed in PubMed, EMBASE, CBM, CNKI, Wanfang Data, and VIP database to collect the case-control studies on the association between smoking and the risk of PBC published in the last two decades. Chinese search words were “吸烟”, “香烟”, “原发性胆汁性肝硬化”, “危险因素”, “队列研究”, and “病例对照研究”, and English search words were “smoking”, “cigarette”, “tobacco”, “risk factors”, “primary biliary cirrhosis”, “cohort studies”, and “case-control studies”. And then a meta-analysis was performed using Review Manager 5.2. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated, and the publication bias was analyzed by funnel plots. ResultsA total of 7 case-control studies involving 5459 subjects (2652 patients with PBC vs 2807 controls) were included in the meta-analysis. The analysis results showed that smokers had a significantly higher risk of PBC compared with non-smokers (OR=1.49, 95% CI: 1.11-2.00, P=0.009). The geographical subgroup analysis results showed that there was a significant difference in the risk of PBC between non-smokers and smokers in North America (OR=1.57, 95% CI: 1.20-2.04, P=0.0008). However, there was no significant difference in the risk of PBC between non-smokers and smokers in Europe (OR=1.41, 95% CI: 0.73-2.73, P=0.31). ConclusionSmoking can increase the risk of PBC. However, it needs to be confirmed in high-quality prospective studies with larger samples because of the heterogeneity of current included studies.
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ObjectiveTo systematically evaluate the association between smoking and the risk of primary biliary cirrhosis (PBC) from the perspective of evidence-based medicine. MethodsA literature search was performed in PubMed, EMBASE, CBM, CNKI, Wanfang Data, and VIP database to collect the case-control studies on the association between smoking and the risk of PBC published in the last two decades. Chinese search words were “吸烟”, “香烟”, “原发性胆汁性肝硬化”, “危险因素”, “队列研究”, and “病例对照研究”, and English search words were “smoking”, “cigarette”, “tobacco”, “risk factors”, “primary biliary cirrhosis”, “cohort studies”, and “case-control studies”. And then a meta-analysis was performed using Review Manager 5.2. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated, and the publication bias was analyzed by funnel plots. ResultsA total of 7 case-control studies involving 5459 subjects (2652 patients with PBC vs 2807 controls) were included in the meta-analysis. The analysis results showed that smokers had a significantly higher risk of PBC compared with non-smokers (OR=1.49, 95% CI: 1.11-2.00, P=0.009). The geographical subgroup analysis results showed that there was a significant difference in the risk of PBC between non-smokers and smokers in North America (OR=1.57, 95% CI: 1.20-2.04, P=0.0008). However, there was no significant difference in the risk of PBC between non-smokers and smokers in Europe (OR=1.41, 95% CI: 0.73-2.73, P=0.31). ConclusionSmoking can increase the risk of PBC. However, it needs to be confirmed in high-quality prospective studies with larger samples because of the heterogeneity of current included studies.
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Objective To study the blood concentration of hydroxychloroquine in patients with systemic lupus erythematosus (SLE) treated with different doses, and analyze the relationship between blood concentration of hydroxychloroquine and disease activity, and evaluate its safety.Methods Forty SLE patients were randomly divided into 2 groups, each group contained 20 cases.The patients in group A were treated with hydroxychloroquine (0.4 g, qd), while patients in group B were treated with hydroxychloroquine (0.2 g, qd).The treatment lasted more than six months in every patient.The blood concentrations of hydroxychloro-quine were detected by high performance liquid chromatography.The clinical and laboratory indices were collected.The systemic lupus erythematosus disease activity index (SLEDAI) score was recorded.The doses and varieties of combined hormone, immunosuppressant were recorded.The correlation of blood concentration of hydroxychloroquine and disease activity was analyzed.The significance was determined by Student's t test and Pearson correlation analysis.Results In SLE patients, the average blood concentration of hydro-xychloroquine was (402±190) ng/ml in group A and (150±60) ng/ml in group B (t=7.471, P＜0.01).The disease activities of patients in the two groups showed no significant difference (t=-0.172, P＞0.05).The platelet counts of patients in group A were significantly higher than those in group B[(188±88)×109/L vs (158 ±87) ×109/L] (t=4.375, P＜0.05).However, the other laboratory parameters showed no significant difference between the two groups (P＞0.05).Conclusion The results of this study indicate that the blood concentrations of hydroxy-chloroquine are significantly different in different dosages.The high dose of hydroxy-chloroquine is related to high platelet number in lupus patients.These findings suggest that hydroxychloroquine is safe and effective for SLE patients.