Ziwan-Taoren herb pair can exert an therapeutical effect in primary Sjogren’s syndrome through inhibiting the TLR/NF-κB pathway

Background:Ziwan and Taoren(ZT)is a classic medicine pair in the formula of Mai Dong Di Shao Decoction,has been used to treat primary Sjogren’s syndrome(pSS)for more than 20 years.But its action mechanism is still unknown.This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS.Methods:Firstly,the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis.Secondly,the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques.Finally,efficacy and mechanism were conducted through in vivo experiments,such as water intake,spleen index,hematoxylin-eosin staining pathological changes,ELISA,Western Blot analysis,and immunofluorescence staining.Results:Nine active compounds were extracted from network pharmacology,including quercitrin,luteolin,kaempferol,β-sitosterol,isorhamnetin,galangin,hederagenin,diosmetin and gibberellin 7.Seven disease targets were identified:RELA,TP53,AKT1,interleukin(IL)6,MAPK1,ESR1,IL10;with RELA being the most core target.KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process.preliminary results of molecular docking showed that ZT’s active compounds bind well to the RELA(p65)receptor.In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice.The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased,while levels of inflammatory factors such as tumor necrosis factor-α,IL-6,and IL-1βalong with protein expressions including toll-like receptor4,p-p65 and p-IKKα/βin NF-κB pathway were reduced.Conclusions:The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS,potentially attributed to its capacity for suppressing the TLR/NF-κB inflammatory signaling pathway.

Higher frequency of brain abnormalities in neuromyelitis optica spectrum disorder patients without primary Sjogren's syndrome

Neuromyelitis optica spectrum disorder often co-exists with primary Sjogreffs syndrome. We compared the clinical features of 16 neuro- myelitis optica spectrum disorder patients with （n = 6） or without primary Sjogreffs syndrome （n = 10）. All patients underwent extensive clinical, laboratory, and MRI evaluations. There were no statistical differences in demographics or first neurological involvement at onset between neuromyelitis optica spectrum disorder patients with and without primary Sjogren＇s syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinudear autoantibody, anti-Sjogren＇s-syndrome-related antigen A an- tibodies, anti-Sjogren＇s-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sjogren＇s syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67% （4/6） of patients with primary Sjogren＇s syndrome and in 60% （6/10） of patients without primary Sj6gren＇s syndrome. More brain abnormalities were observed in patients without primary Sj6gren＇s syndrome than in those with primary Sj6gren＇s syndrome. Segments lesions （〉 3 centrum） were noted in 50% （5/10） of patients without primary Sj6gren＇s syndrome and in 67% （4/6） of patients with primary Sjogren＇s syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sjogren＇s syndrome are similar. However, neu- romyelitis optica spectrum disorder patients without primary Sjogreffs syndrome have a high frequency of brain abnormalities.

Gastrointestinal microbiome and primary Sjogren’s syndrome: a review of the literature and conclusions

The recognition of the profound impact of the human gastrointestinal microbiome(GM) on human autoimmune diseases has gradually increased thanks to deeper research efforts. As a systemic autoimmune disease, primary Sjogren’s syndrome(pSS) cannot be completely cured. Human studies have revealed that GM species and diversity are altered in patients with p SS compared with healthy individuals. Animal studies have provided possible mechanisms for the association between pSS and GM. The potential role of GM in pSS is exerted through several mechanisms. GM dysbiosis leads to increased intestinal permeability, which increases the risk of GM antigen exposure and activates specific autoreactive T lymphocytes via “molecular mimicry”. In addition, GM antigen exposure and intestinal immune tolerance loss caused by GM dysbiosis together induce chronic local gut mucosal inflammation, which deteriorates to systemic chronic non-specific inflammation with the circulation of pro-inflammatory lymphocytes and cytokines. These factors eventually activate autoreactive B lymphocytes and lead to pSS. If GM plays a key role in the pathogenesis of pSS, clarifying the underlying mechanisms will be helpful for the development of new therapies targeting GM for dry eye associated with pSS. This review summarizes the latest knowledge about the relationship between GM and p SS,with the aim of contributing to future research and to the development of new clinical applications.

EVALUATION OF INTERNATIONAL CLASSIFICATION CRITERIA (2002) FOR PRIMARY SJGREN'S SYNDROME IN CHINESE PATIENTS

Objective To evaluate the sensitivity and specificity of international classification criteria （2002） for primary Sjogren＇s syndrome （pSS） and the role of lower lip biopsy in diagnosis of pSS in Chinese patients. Mothoda Patients who were diagnosed by the experts/rheumatologists as pSS during 1990-2002 from the Department of Rheumatology, Peking Union Medical College Hospital were retrospectively collected as experimental group. Patients who were diagnosed as non-pSS connective tissue diseases or non-connective tissue diseases served as control group. Those with a history of head-neck radiation, hepatitis C virus infection, AIDS, lymphoma, sarcoidosis, graft versus host disease （GVHD）, and anti-acetylcholine drug use were exempted. Both groups were required to complete questionnaires about symptoms such as dry eyes and dry mouth, and complete the objective tests of keratoconjunctivitis and xerostomia including Schirmer test, corneal staining, unstimulated salivary flow, sialography, lower lip biopsy, and antinuclear antibodies （including anti-SSA/SSB antibodies） test. Results A total of 330 pSS patients were included in experimental group and 185 non-pSS patients in control group. The mean age of both groups matched （47.8 ± 10.9 years vs. 46.2±13.6 years, P 〉 0.05）. The sensitivities of the criteria in pSS patients with lower lip biopsy and in pSS patients without lower lip biopsy were 89.2% and 87.2%, respectively; the overall sensitivity was 88.5%. The specificity was 97.3%. A total of 11.3% pSS patients with negative anti-SSA/SSB antibodies were diagnosed as pSS by lower lip biopsy. Coadwion The international classification criteria （2002） for pSS is feasible in Chinese patients. It has high sensitivity and specificity, and may serve as diagnosis criteria in routine clinical practice.

原发性干燥综合征患者抗SSB与其他实验室参数相关性研究

目的探讨原发性干燥综合征(pSS)患者自身免疫性抗体抗干燥综合征B抗体(抗SSB)、抗干燥综合征A抗体(抗SSA)60、抗SSA52在疾病活动性评价中的价值。方法收集152例pSS患者临床资料及实验室数据进行回顾性分析,相关实验室数据包括血常规、C反应蛋白(CRP)、红细胞沉降率(ESR)、类风湿因子(RF)、免疫球蛋白(Ig)A、IgG、IgM、补体C3、补体C4、抗SSB、抗SSA60、抗SSA52,根据患者抗SSB、抗SSA60、抗SSA52检测结果进行分组统计分析。结果152例pSS患者中抗SSB患者阳性率为35.5%,抗SSA60患者阳性率为61.8%,抗SSA52患者阳性率为71.7%。抗SSB+患者红细胞计数(RBC)、血红蛋白(Hb)、白细胞计数(WBC)水平明显低于抗SSB-患者,ESR、IgG、RF水平明显高于抗SSB-患者(P<0.05);抗SSA60+患者年龄、WBC、血小板计数(PLT)明显低于抗SSA60-患者,IgG、RF水平明显高于抗SSA60-患者(P<0.05);抗SSA52+患者IgG、RF水平明显高于抗SSA52-患者(P<0.05)。抗SSB与抗SSA60、抗SSA52呈正相关(r=0.563、0.414,P<0.05)。结论抗SSB+pSS患者存在更严重的血液系统损伤,早期pSS患者应进行抗SSB检测并注意随访。

Ro60不同表位自身抗体在SLE和pSS淋巴细胞减少中的作用

目的初步探讨Ro60不同表位自身抗体在系统性红斑狼疮(SLE)和原发性干燥综合征(pSS)患者淋巴细胞(LC)减少中的作用。方法 SLE患者16例,pSS患者14例,均为女性,所有患者病情处于活动期,3个月内未接受过糖皮质激素和免疫抑制剂治疗,Ro60抗体阳性,周围血淋巴细胞低于1×109/L,SLE和pSS组LC计数分别为(0.66±0.12)×109/L和(0.70±0.16)×109/L(P=0.511),另选择健康对照者10例。体外培养3组患者的外周血LC,加入Ro60抗原3个不同表位(aa482-493、aa310-323和aa230-241)的免疫毒素(IT)(AE1、AE2和AE3),MTT法分别检测其对患者LC的毒性,分析患者不同表位IT的细胞毒性与LC计数的关系,同时比较检测2组患者周围血相应表位的自身抗体。结果 3个IT对体外培养的对照组LC均有一定毒性,但AE3和AE2分别对SLE和pSS患者的LC表现有显著增强的细胞毒性,且与患者的淋巴细胞减少程度显著相关(SLE组r=0.653,P=0.06;pSS组r=0.594,P=0.025),两组患者的周围血中3个相应表位的自身抗体阳性率并无显著差异。结论 Ro60自身抗体在SLE和pSS患者LC减少中可能发挥作用,但在两种疾病中其作用机制可能不完全相同。

Changes of Intestinal Microecology in Patients with Primary Sjogren’s Syndrome after Therapy of Yangyin Yiqi Huoxue Recipe(养阴益气活血方)

Objective: To explore the change of intestinal microecology in patients with primary Sjogren’s syndrome(p SS) and correlation with disease activity, and also discuss the therapy effect of Yangyin Yiqi Huoxue Recipe(养阴益气活血方, YYHD). Methods: Sixteen p SS patients were enrolled in the present study, who received 3-month treatment of YYHR, 200 mL orally twice daily. Their pre-and post-test ESSDAI scores, erythrocyte sedimentation rate(ESR) and serum immunoglobulin G(IgG) levels were measured respectively. The 16 Sr DNA metagenomic sequencing was used to detect and analyze the abundance and diversity of intestinal bacteria flora and the proportion of bacteria at the levels of phylum, family, and genus, in comparision with those of 6 healthy subjects in the control group. Results: The abundance and diversity of intestinal bacteria flora in pSS patients were lower than those of healthy subjects(P<0.05). After the treatment with YYHD, patients’ ESSDAI score and levels of IgG and ESR have decreased significantly(P<0.05). At the phylum level, the proportions of Actinobacteria, Firmicutes, Fusobacteria and Proteobacteria have reduced sharply, while the proportions of Bacteroidetes, Teneriquetes and Candidate-division-TM7 have increased significantly by treatment(all P<0.05). At the classification level, such treatment has caused a significant decrease in the proportions of Bacteroidaceae, Ruminococcaceae, Veillonellaceae, and Enterobacteriacea(all P<0.05), but a significant increase in the proportion of Lachnospiraceae(P<0.05). At the genus level, the treatment has significantly decreased the proportions of Bifidobacterium, Bacteroides, Escherichia-Shigella, Faecalibacterium and Prevotella(all P<0.05), but significantly increased the proportion of Clostridia(P<0.05), close to the levels of healthy subjects(P>0.05). Conclusions: There exists an imbalance of intestinal microecology in p SS patients, which can be improved through the treatment with YYHD. Besides, such treatment can also improve the disease activity and adjust the diversity of intestinal bacteria flora, the composition and the abundance of intestinal flora.

Meta-analysis of the efficacy in treatment of primary sjogren's syndrome: Traditional Chinese Medicine vs Western Medicine

OBJCTIVE: To compare the clinical efficacy of Traditional Chinese Medicine(TCM) to Western Medicine in the treatment of primary Sj?gren's syndrome(p SS).METHODS: We collected randomized controlled trials of TCM vs Western Medicine for the treatment of p SS in Chinese and foreign databases. The study quality was evaluated as suggested in the Cochrane Handbook. The Meta-analysis was performed using Review Manager 5.0 statistical software.RESULTS: A total of 31 randomized controlled trials with 2137 cases were retrieved. The efficiencies of TCM and control treatments were 87.18% and65.63%, respectively. The results of heterogeneity tests showed that the data were homogeneous(P = 0.83), thus a fixed effects model was used for analysis. The results revealed an odds ratio of 3.74 with a 95% confidence interval of 2.99-4.69. The overall effectiveness value was 11.48(P < 0.000 01).These results suggest the efficacy of TCM therapy for p SS better than Western Medicine.CONCLUSION: Although our findings reveal that the TCM treatment of p SS had significant advantages over its counterpart, there were some flaws in the studies included. The findings warrant further investigation.

Effect of Chinese Herbal Medicine for Nourishing Yin,Supplementing Qi,and Activating Blood on the Th1/Th2 Immune Balance in Peripheral Blood in Patients with Primary Sjogren's Syndrome

Objective： To observe the effect of Chinese herbal medicine for nourishing yin, supplementing qi, and activating blood on the expression of interferen- γ （IFN-γ,）/interleukin-4 （IL-4） in peripheral blood and disease activity in primary Sjogren＇s syndrome （pSS） patients, and to study the relationship between the immune balance of Th1/Th2 and the disease activity. Methods： A total of 66 pSS patients were randomized with tossing coins method into two groups： the integrative therapy group （34 cases） and the control group （32 cases）; and 28 healthy subjects were taken as the normal group. The integrative therapy group was treated by Chinese herbal medicines for nourishing yin, supplementing qi, and activating blood combined with hydroxychloroquine sulfate tablets and the control group was treated with hydroxychloroquine sulfate tablets. The treatment course was 3 months for both groups. The levels of serum immunoglobulin G （IgG）, erythrocyte sedimentation rate （ESR）, IFN-γand IL-4 in peripheral blood were measured before and after treatment. Results： Compared with the normal group, the levels of IgG, ESR, IFN- γ and IL-4 were significantly increased in pSS patients （P〈0.05）. Remarkably, after 3 months of treatment, these levels were dramatically decreased in both the integrative therapy group and the control group, although still higher than the normal group. The levels of IgG, ESR, IFN- and IL-4 in the integrative therapy group were lower than the control group and the same group before treatment （P〈0.05）. The ratio of IFN-γ/IL-4 also significantly decreased after treatment. Moreover, the level of IFN- γ, and the ratio of IFN- γ/IL-4 in the integrative theraphy group were significantly lower than the control group （P〈0.05）. For all patients the ratio of IFN-γ/IL-4 before and after treatment was positive correlated with the levels of IgG and ESR. Conclusion： Chinese herbal medicine for nourishing yin, supplementing qi, and activating blood can alleviate the disease activity of pSS by regulating the immune balance of Th1/Th2.

Therapeutic Effect of Chinese Herbal Medicine for Strengthening Qi,Nourishing Yin,and Removing Stasis on Serum Osteopontin and Quality of Life of Patients with Primary Sjogren's Syndrome

Objective：To observe the therapeutic effect of Chinese herbal medicine for strengthening qi, nourishing yin,and removing stasis on serum osteopontin（OPN） and quality of life（QOL） in patients with primary Sjogren＇s syndrome（pSS） and to study the correlation between OPN level and the disease.Methods：Sixtyeight pSS patients were randomly assigned to two groups：the treatment group（35 cases） treated by Chinese herbal medicine for strengthening qi,nourishing yin,and removing stasis combined with hydroxychloroquine sulfate tablet（HCQ） and the control group（33 cases） treated by HCQ only.Both were treated for 3 months. Before and after treatment,immunoglobulin G（IgG） level,erythrocyte sedimentation rate（ESR）,and OPN level were measured.The QOL in patients was evaluated using the Short Form-36 Health Survey（SF-36） before and after treatment.Thirty healthy females were taken as the normal control.Results：Before treatment,levels of IgG,ESR,and OPN in patients were higher than those in the normal control.After 3 months of treatment, those in both treatment groups decreased but were lower in the treatment group than those in the control group （P0.05）.The scores of 8 dimensions of SF-36 were lower in the pSS patients than those in the normal control （P0.05） and higher in the treatment group than in the control group after treatment（P0.05）.Furthermore, there was a positive correlation between the levels of OPN and the levels of IgG and ESR,and a negative correlation between OPN levels and the overall score of SF-36（P0.05）.Conclusions：Chinese herbal medicine for strengthening qi,nourishing yin,and removing stasis could alleviate pSS disease and improve the QOL.In addition,the OPN level might be used as an evaluating index for pSS disease.

Effect of Chinese Herbal Medicines for Nourishing Yin,Supplementing Qi,and Activating Blood on Reproductive Endocrine Activity and Immune Functions in Patients with Primary Sjogren's Syndrome

ABSTRACT Objective： To investigate the effect of Chinese herbal medicines for nourishing yin, supplementing qi, and activating blood on the reproductive endocrine-immune network and its mechanisms in patients with primary Sjogren＇s syndrome （pSS）. Methods： Seventy pSS patients were randomly assigned to two groups using a randomized digital table： the integrative therapy group （36 cases） and the control group （34 cases）. Thirty healthy subjects were taken as a normal group. The control group was treated with hydroxychloroquine sulfate tablets alone, and the integrative therapy group was treated by Chinese herbal medicines for nourishing yin, supplementing qi, and activating blood combined with hydroxychloroquine sulfate tablets. The treatment course was 6 months for both groups. Before and after treatment, serum estradiol （E2）, testosterone （T）, luteinizing hormone （LH）, prolactin （PRL） by radioimmunoassay and immunoglobulin （IgG） by immunodiffusion, erythrocyte sedimentation rate （ESR） by Westergren, interferon-γ （IFN-γ） and interleukin-4 （IL-4） by enzyme linked immunosorbent assay were determined. Results： E2 and T levels in all patients were lower than those of normal subjects before treatment （P〈0.05） and were increased significantly after 6-month treatment （P〈0.05）. ESR, FSH, LH, IgG, IFN - γ, IL - 4 and ratios of E2/T, and IFN --γ/IL in the patients were higher than those of normal subjects before the treatments （P〈0.05）, and were reduced significantly after the treatments （P〈0.05）. The T and IFN -γ levels and E2/T ratio in the patients treated with integrative therapy were reduced significantly compared with the control group （P〈0.05）. However, the PRL levels before and after treatment were not significantly changed in the two groups （P〉0.05）. The ratios of E2/T and IFN -γ/IL-4, and levels of IgG and ESR were positively correlated before and after treatment （P〈0.05）. Conclusions： The ratios of E2/T and IFN - γ/ IL-4 might be used as indicators of pSS activity. Chinese herbal medicines for nourishing yin, supplementing qi, and activating blood combined with Western medicine could improve the therapeutic effect by regulating the reproductive endocrine-immune network in pSS patients.

Clinical Profile and Significance of Mucocutaneous Lesions of Primary Sjogren＇s Syndrome： A Large Cross-sectional Study with 874 Patients

Background： Mucocutaneous lesions are common features of primary Sjogren＇s syndrome （pSS）, but only a few studies have focused on them. To demonstrate the profile ofmucocutaneous lesions ofpSS and further explore their potential clinical significance, we perfermed a cross-sectional study on 874 patients. Methods： Demographic data, clinical manifestations, and laboratory results of 874 pSS patients were collected. Patients were divided into two groups according to the presence of mucocutaneous lesions. Differences in primary symptoms and systemic impairments between the two groups were analyzed. Results of laboratory tests were also compared alter excluding those who had taken corticosteroid from both groups. One-year follow-up was done, and occurrences of various new complications were compared. Results： Among the 874 pSS patients, 181 patients had mucocutaneous lesions, accounting for 20.7%. Multiple mucocutaneous manifestations were displayed, and the top four most common types of lesions were purpuric eruptions （39.8%）, urticaria （23.8%）, Raynaud＇s phenomenon （14.9%）, and angular stomatitis （9.9%）. Incidences of pulmonary interstitial fibrosis, pulmonary bullae, leukopenia, and anemia were significantly higher among patients with mucocutaneous lesions （P 〈 0.05）. Increase in lgG and decrease in C4 among patients with mucocutaneous lesions displayed statistical significance after excluding patients from both groups who had taken corticosteroid （P 〈 0.05）. Alter one-year follow-up, patients with mucocutaneous lesions presented a slightly higher incidence of new complications compared to those without. Conclusions： Mucocutaneous manifestations ofpSS patients were common and diverse. Patients with mucocutaneous manifestations had more systemic damages, higher level of IgG, and lower level of serum C4, suggesting a higher activity of the primary disease.

基于胸部CT及临床特征构建原发性干燥综合征患者肺脏受累的风险预测模型

目的基于胸部CT及临床特征构建原发性干燥综合征(primary Sjogren′s syndrome,pSS)患者肺脏受累的风险预测模型,并探讨模型的风险预测价值。方法回顾性选取邯郸市中医院于2020年10月至2023年8月收治的360例pSS患者为研究对象,按照7∶3的分配比例分为建模组252例和验证组108例。建模组患者根据肺脏受累与否分为对照组201例和受累组51例。收集建模组患者临床特征资料与胸部高分辨CT(high resolution CT,HRCT)特点,行组间单因素分析确定收集信息中影响pSS患者肺脏受累的相关因素。对相关因素行二元logistic回归分析以筛选独立危险因素,并以独立危险因素建立预测模型,通过验证组资料收集配合完成列线图预测模型的验证与价值分析。结果患者年龄、病程、咳嗽、雷诺现象、C反应蛋白(C-reactive protein,CRP)、抗SSA抗体、HRCT等为影响pSS患者肺脏受累的相关因素(P<0.05)。进一步行二元logistic回归分析发现,患者年龄大、病程长、咳嗽及HRCT异常为影响SS患者肺脏受累的独立危险因素(P<0.05)。以独立影响因素构建列线图风险预测模型,模型验证结果提示,校准图显示预测模型性能良好;建模组受试者工作特征(ROC)曲线的曲线下面积(AUC)为0.993;验证组ROC的AUC为0.995。结论pSS患者临床特征与胸部CT结果与患者肺脏受累密切相关,其中患者年龄大、病程长、咳嗽及HRCT异常为影响pSS患者肺脏受累的独立危险因素,以此为基础建立预测模型对患者后装放疗是否发生肺脏受累具有较高预测价值。

组织蛋白酶S在原发性干燥综合征中的临床意义

目的探讨组织蛋白酶(Cathepsin,Cat)S在原发性干燥综合征(primary Sjgren’s syndrome,p SS)患者中的临床意义。方法通过酶联免疫吸附法检测p SS患者及健康对照组血清总Cat S和pro-Cat水平,并分析比较其在p SS患者血清中的变化及其与欧洲抗风湿联盟p SS疾病活动度(EULAR Sjgren’s syndrome disease activity index,ESSDAI)评分和Ig G水平之间的相关性;免疫组化检测唇腺组织Cat S的表达。采用受试者工作特征曲线(receiver operating characteristic curve,ROC曲线)、t检验、Spearman相关性分析进行统计学分析。结果 p SS组(n=37)血清总Cat S、pro-Cat S和active-Cat S表达水平高于健康对照组(n=33),差异有统计学意义[总Cat S(18.70±2.53)ngml vs.(15.10±3.16)ngml;pro-Cat S(14.14±3.56)ngml vs.(12.20±2.92)ngml;active-Cat S(4.56±2.49)ngml vs.(2.90±1.95)ngml,P<0.05];而高免疫球蛋白血症(Ig G>25 gL)组与非高免疫球蛋白组比较,三者表达水平差异无统计学意义(P>0.05)。p SS患者血清总Cat S、proCat S及active-Cat S水平与ESSDAI评分及血清Ig G水平无明确相关性(P>0.05)。以2002年p SS国际分类诊断标准作为参照,ROC分析发现,血清总Cat S、pro-Cat S和active-Cat S水平曲线下面积分别为0.811(P<0.01)、0.655(P<0.01)和0.701(P<0.01);最佳阈值分别为15.77、12.62、4.06 ngml;敏感性和特异性分别为0.919和0.697、0.676和0.667、0.622和0.758。唇腺组织免疫组化发现p SS患者唇腺腺上皮细胞、导管上皮细胞及淋巴细胞均表达Cat S升高,而对照者未见明显表达。结论血清总Cat S、pro-Cat S、active-Cat S升高,唇腺组织表达Cat S升高,可能通过增强自身抗原呈递、降解细胞外基质、促进淋巴细胞浸润等作用,在p SS患者发病中发挥重要作用,这也为p SS患者提供了一种新的血清学标志物及潜在的治疗靶点。

原发性干燥综合征住院患者的中医证素研究

【目的】探究原发性干燥综合征(燥痹)住院患者的中医证素分布规律。【方法】以2012年1月至2022年12月期间在广东省中医院接受治疗的符合纳入、排除标准的240例原发性干燥综合征住院患者为研究对象,对证素信息进行数据挖掘。【结果】(1)240例患者中,男21例(占8.75%),女219例(占91.25%),以女性患者居多;年龄方面,青年患者(18~45岁)33例(占13.75%),中年患者(46~69岁)148例(占61.67%),老年患者(70岁~)59例(24.58%),以中年患者居多。(2)240例患者中,有4例无证素诊断成立,236例统计到证素诊断,共得到38个证素,其中病位证素15个,病性证素23个,证素总频次为1142例次。频数最多的病位证素为肝(6.04%)、肺(4.99%)、筋骨(4.20%);频数最多的病性证素为阴虚(13.75%)、气虚(9.37%)、痰(6.57%)。病位证素中,以单病位证素为主(42.92%);病性证素中,以5个以上病性证素为主(25.83%)。不同性别的脾、阴虚证素分布比较,差异有统计学意义(P<0.05);不同年龄段的气虚、饮证素分布比较,差异有统计学意义(P<0.05)。频数最高的证素组合为气虚+阴虚(72次,30%)、痰湿+阴虚(72次,30%),其次为热+阴虚(59次,24.58%)。根据证素组合得到240例原发性干燥综合征的常见中医证型为气阴两虚、阴虚痰湿、阴虚火旺等。【结论】原发性干燥综合征常累及肝、肺等,以阴虚、气虚多见,证素混杂,以气阴两虚为常见证型,提示从证素出发对原发性干燥综合征进行辨治更具有针对性。

原发性干燥综合征患者血清sHLA-G检测分析

目的:探讨血清可溶性人类白细胞抗原-G(sHLA-G)含量与原发性干燥综合征(pSS)的关系。方法:用酶联免疫吸附测定(ELISA)法检测71例pSS患者和69例健康对照者血清中sHLA-G含量。结果:69例健康人血清sHLA-G的浓度最低为1.43U/mL,最高为32.76U/mL,平均值范围(14.35±8.88)U/mL。71例pSS患者sHLA-G的浓度最低为1.05U/mL,最高为28.82U/mL,平均值范围(8.43±7.24)U/mL。pSS患者血清sHLA-G水平显著低于健康对照组(P<0.01)。结论:pSS患者血清sHLA-G水平显著降低,sHLA-G水平降低可能参与了pSS的病理过程。

原发性干燥综合征患者唇腺组织γ-干扰素、Fas、FasL的表达及意义

目的通过检测原发性干燥征(PSS)患者唇腺组织中γ-干扰素(IFN-γ)、Fas、FasL的表达情况,探讨它们在PSS患者和对照者的表达是否有差异,以及γ-干扰素、Fas、FasL间的相互关系,进一步探讨γ-干扰素、Fas、FasL在PSS发病机制中的作用及意义。方法采用免疫组织化学法测定20例PSS患者及8例对照者唇腺γ-干扰素、Fas、FasL阳性细胞数。结果 PSS患者唇腺组织γ-干扰素、Fas、FasL高表达于导管、腺泡上皮细胞,高于对照组(P<0.05);PSS患者唇腺组织γ-干扰素、Fas、FasL的表达均呈正相关(P<0.05)。结论γ-干扰素、Fas、FasL在PSS患者唇腺组织中存在异常表达,提示γ-干扰素、Fas、FasL可能参与PSS的发病过程。

血清淀粉样蛋白酶P(SAP)在3种常见结缔组织病患者中的表达及其意义

目的:研究血清淀粉样蛋白P(SAP)在3种常见结缔组织病患者血清中含量,探讨其在结缔组织病发生发展中的作用及意义。方法:用ELISA方法测定正常人、系统性红斑狼疮活动期和缓解期、类风湿关节炎活动期和缓解期、初治干燥综合征等风湿性疾病血清中血清淀粉样蛋白P(SAP)含量。统计各型患者血清中血清淀粉样蛋白P(SAP)的表达水平及其意义。结果:SAP在系统性红斑狼疮患者活动期血清中高表达,且其表达水平显著高于缓解期和正常人,差异均有统计学意义(P<0.05)。结论:血清淀粉样蛋白P(SAP)在系统性红斑狼疮活动期高表达,可以作为系统性红斑狼疮患者活动期的诊断指标之一。

Traditional Chinese medicine is a useful and promising alternative strategy for treatment of Sjogren’s syndrome:A review

Primary Sjogren’s syndrome(p SS)is a chronic autoimmune disease involving exocrine glands.Current studies have found that the occurrence of the disease is closely related to genetic,environmental and neuroendocrine factors,as well as abnormal activation of T and B lymphocytes.The etiology and pathogenesis of p SS is complex,and there is a lack of specific targeted drugs.Traditional Chinese medicines(TCMs)have been comprehensively investigated for their treatment effects on p SS.Through a systematic review of the literature,we summarized the TCMs used to treat p SS,and find that there are four major ways that TCMs are used,including upregulation of aquaporin proteins,suppression of cell apoptosis,suppression of the abnormal activation of B lymphocytes and suppression of the abnormal activation of T lymphocytes(balancing T helper type[Th]1/Th 2& Th17/Treg and suppressing follicular helper T[Tfh]cells).However,there are not enough data about the active constituents,quality control,pharmacokinetics,toxicity and modern preparations of these TCMs;therefore,more investigations are needed.This paper highlights the importance of TCMs for treating p SS and provides guidance for future investigations.

原发性干燥综合征患者唾液腺中染色质调节因子相关基因的表达分析及其与免疫浸润的关系

目的分析染色质调节因子(CRs)相关基因在原发性干燥综合征(pSS)患者唾液腺中的表达情况,并探讨其与pSS患者唾液腺免疫浸润的相关性。方法通过下载并整合基因表达综合数据库(GEO)的3个包含pSS患者和健康对照者唾液腺基因表达阵列的数据集,纳入38例pSS患者作为pSS组,32例健康对照者作为对照组,并对22189个基因的表达情况进行分析,包括筛选与CRs有关的差异表达基因(DEGs)、基因本体论(GO)富集分析。所有数据集都在R语言(4.0.3)中使用相关程序包进行分析,采用ssGSEA算法获得不同免疫细胞和免疫功能的免疫浸润评分,并对不同免疫细胞间和不同免疫功能间的免疫浸润评分进行相关性分析。对pSS组和对照组的免疫浸润评分进行差异分析。结果从22189个基因中共筛选出850个与CRs有关的基因表达,差异分析共筛选出11个DEGs,其中包括10个上调基因和1个下调基因。GO富集分析提示,频率最高的4种生物学过程为正向调控DNA修复、调节DNA损伤刺激反应、非同源端连接修复双链DNA和DNA修复,所涉及的细胞组分包括性染色体、PML核体、染色体端粒和核心蛋白复合体。对免疫细胞的相关性分析提示,肿瘤浸润淋巴细胞(TIL)和B细胞的相关性最高(r=0.90,P<0.001),其次为滤泡辅助性T细胞(Tfh)和TIL(r=0.72,P<0.001);在免疫功能方面,免疫检查点和T细胞共刺激的相关性最高(r=0.92,P<0.001),其次为免疫检查点和CC趋化因子受体(r=0.89,P<0.001)。pSS组9种免疫细胞和8种免疫功能的免疫浸润评分较对照组显著上调(P<0.05)。结论pSS患者唾液腺中DEGs数量较少,但是与受损唾液腺免疫浸润异常有关,值得临床医生的关注。