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.

Management of primary ciliary dyskinesia/Kartagener＇s syndrome in infertile male patients and current progress in defining the underlying genetic mechanism

Kartagener＇s syndrome （KS） is an autosomal recessive genetic disease accounting for approximately 50% of the cases of primary ciliary dyskinesia （PCD）. As it is accompanied by many complications, PCD/KS severely affects the patient＇s quality of life. Therapeutic approaches for PCD/KS aim to enhance prevention, facilitate rapid definitive diagnosis, avoid misdiagnosis, maintain active treatment, control infection and postpone the development of lesions. In male patients, sperm flagella may show impairment in or complete absence of the ability to swing, which ultimately results in male infertility. Assisted reproductive technology will certainly benefit such patients. For PCD/KS patients with completely immotile sperm, intracytoplasmic sperm injection may be very important and even indispensable. Considering the number of PCD/KS susceptibility genes and mutations that are being identified, more extensive genetic screening is indispensable in patients with these diseases. Moreover, further studies into the potential molecular mechanisms of these diseases are required. In this review, we summarize the available information on various aspects of this disease in order to delineate the therapeutic objectives more clearly, and clarify the efficacy of assisted reproductive technology as a means of treatment for patients with PCD/KS-associated infertility.

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.

Primary aldosteronism due to bilateral micronodular hyperplasia and concomitant subclinical Cushing’s syndrome:A case report

BACKGROUND Adrenal incidentaloma(AI)has been frequently encountered in the clinical setting.It has been shown that primary aldosteronism(PA)or subclinical Cushing’s syndrome(SCS)are the representative causative diseases of AI.However,the coexistence of PA and SCS has been reportedly observed.Recently,we encountered a case of AI,in which PA and SCS coexisted,confirmed by histopathological examinations after a laparoscopic adrenalectomy.We believe that there were some clinical implications in the diagnosis of the present case.CASE SUMMARY A 58-year-old man presented with lower right abdominal pain with a blood pressure of 170/100 mmHg.A subsequent computed tomography scan revealed right ureterolithiasis,which was the cause of right abdominal pain,and right AI measuring 22 mm×25 mm.After the disappearance of right abdominal pain,subsequent endocrinological examinations were performed.Aldosterone-related evaluations,including adrenal venous sampling,revealed the presence of bilateral PA.In addition,several cortisol-related evaluations showed the presence of SCS on the right adrenal adenoma.A laparoscopic right adrenalectomy was then performed.The histopathological examination of the resected right adrenal revealed the presence of a cortisol-producing adenoma,while CYP11B2 immunoreactivity was absent in this adenoma.However,in the adjacent nonneoplastic adrenal,multiple CYP11B2-positive adrenocortical micronodules were detected,showing the presence of aldosterone-producing adrenocortical micronodules.CONCLUSION Careful clinical and pathological examination should be performed when a patient harboring AI presents with concomitant SCS and PA.

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.

Iguratimod in treatment of primary Sjögren’s syndrome concomitant with autoimmune hemolytic anemia:A case report

BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.However,there are few reports about the application of IGU in pSS concomitant with AIHA.CASE SUMMARY Here,we present the case of a patient with pSS concomitant with AIHA but without eye and mouth dryness.The patient was initially diagnosed with hyperplastic anemia and AIHA while pSS was missed,and was finally diagnosed with pSS concomitant with AIHA.The patient was treated with IGU along with prednisone and hydroxychloroquine,and her hemoglobin,reticulocytes and IgG returned to normal levels.CONCLUSION IGU was effective for and well tolerated by our patient with pSS concomitant with AIHA,and may be a promising therapy for the treatment of this disease.

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.

Concomitant extrahepatic autoimmune diseases do not compromise the long-term outcomes of primary biliary cholangitis

Background:Primary biliary cholangitis(PBC)patients often have concomitant extrahepatic autoimmune(EHA)diseases including Sjögren’s syndrome(SS),systemic sclerosis(SSc),rheumatoid arthritis(RA),and autoimmune thyroid disease.The present study aimed to describe the prevalence of EHA diseases in PBC and explore the impact of EHA diseases on the long-term outcomes of PBC in Chinese patients.Methods:Medical records of PBC patients diagnosed in our institute were retrospectively reviewed.Pa-tients were followed up by a standardized telephone interview.The endpoints were defined as liver-related death and/or liver transplantation.Results:Totally 247 of the 985(25.1%)PBC patients enrolled in the study had at least one concomi-tant EHA disease.Sjögren’s syndrome(n=140,14.2%)was the most frequent one,followed by rheuma-toid arthritis(RA)(n=56,5.7%)and Hashimoto’s thyroiditis(n=45,4.6%).Patients with EHA dis-eases were more common in females(P<0.001)and in those with a family history of autoimmune disease(P=0.017).Overall,no differences were found between PBC patients with and without EHA dis-eases in terms of biochemical response rates to ursodeoxycholic acid,the incidence of hepatic events,or transplant-free survival.RA and EHA≥2 were protective factors for hepatic events in univariate Cox analysis,but the results became insignificant in multivariate analysis.Conclusions:Concomitant EHA diseases were common in PBC patients but did not compromise the long-term outcomes of PBC.

Clinical spectrum of primary ciliary dyskinesia in childhood

Although the triad of bronchiectasis, sinusitis and situs inversus was first described by Kartagener in 1933, the clinical spectrum of primary ciliary dyskinesia is still under investigation. Heterotaxy defects as well as upper and lower respiratory tract symptoms are the main manifestations in childhood. It is now recognized that situs inversus is encountered in only half of patients. The first lower respiratory symptoms may be present from infancy as neonatal respiratory distress. The most common lower airway manifestations are chronic wet cough, recurrent pneumonia and therapy resistant wheezing. Patients are at risk of developing bronchiectasis which may even be the presenting finding due to delayed diagnosis. Upper respiratory tract infections such as nasal congestion, nasal drainage and recurrent sinusitis as well as otologic manifestations such as otitis media or otorrhea with conductive hearing loss are also often encountered. It seems that the type of ciliary ultrastructure defects and the involved mutated genes are associated to some extent to the clinical profile. The disease, even in nowadays, is not recognized at an early age and the primary care clinician should have knowledge of its clinical spectrum in order to select appropriately the children who need further investigation for the diagnosis of this disorder.

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。

Role of JAK-STAT signaling pathway in pathogenesis and treatment of primary Sjögren’s syndrome

Primary Sjögren’s syndrome(pSS)is a systemic autoimmune disease with high prevalence and possible poor prognosis.Though the pathogenesis of pSS has not been fully elucidated,B cell hyperactivity is considered as one of the fundamental abnormalities in pSS patients.It has long been identified that Janus kinases-signal transducer and activator of transcription(JAK-STAT)signaling pathway contributes to rheumatoid arthritis and systemic lupus erythematosus.Recently,increasing numbers of studies have provided evidence that JAK-STAT pathway also has an important role in the pathogenesis of pSS via direct or indirect activation of B cells.Signal transducer and activator of transcription 1(STAT1),STAT3,and STAT5 activated by various cytokines and ribonucleic acid contribute to pSS development,respectively or synergically.These results reveal the potential application of Janus kinase inhibitors for treatment of pSS,which may fundamentally improve the quality of life and prognosis of patients with pSS.

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。

ETS1基因多态性与原发性干燥综合征的相关性

目的探讨ETS1基因单核苷酸多态性(single nucleotide polymorphism,SNP)与汉族人群原发性干燥综合征(primary sjgren’s syndrome,pSS)遗传易感性是否相关。方法提取261例pSS患者和597例健康对照者的全基因组DNA。使用Sequenom MassArray方法对ETS1基因上2个SNP位点(rs6590330和rs1128334)进行基因分型。分型结果使用PLINK 1.07软件进行统计分析。结果 rs6590330位点GG、GA、AA基因型频率和G、A等位基因频率分布在pSS组和对照组间差异无统计学意义(均P>0.05)。加性模型、显性模型、隐性模型下的分析显示,两组间差异仍无统计学意义(均P>0.05)。将pSS患者按照性别及抗SSA和抗SSB抗体产生情况分组,分析仍未发现任何相关性。rs1128334分型成功率过低无法分析。结论 ETS1基因的SNP位点rs6590330与汉族人群pSS患者遗传易感性不相关。

原发性失眠患者中医证型与神经肽S受体基因rs324981多态性的相关性

目的:探讨原发性失眠(PI)患者中医证型与神经肽S受体(NPSR)基因rs324981多态性的相关性。方法:纳入154例PI患者,进行中医辨证分型,并匹配130名健康者为对照组。采用匹兹堡睡眠质量指数量表(PSQI)评估受试者睡眠质量。使用Mass ARRAY SNP基因分型技术检测受试者NPSR基因rs324981多态性,并分析PI患者不同中医证型与NPSR基因rs324981多态性的相关性。结果:154例PI患者中医辨证为肝郁化火证47例(30.52%),痰热内扰证16例(10.39%),阴虚火旺证60例(38.96%),心脾两虚证24例(15.58%),心虚胆怯证7例(4.55%)。PI阴虚火旺证患者NPSR基因rs324981多态性基因型分布与对照组比较,差异有统计学意义[P=0.034,OR=2.10,95%CI(1.05, 4.19)]。PI虚证和实证与对照组NPSR基因rs324981多态性的基因型和等位基因分布比较,差异均无统计学意义(P>0.05)。结论:PI患者阴虚火旺证可能与NPSR基因rs324981多态性存在相关性。

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。

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。

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.

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.

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.