Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine： Sjögren's Syndrome / 中国实验方剂学杂志

Sjögren's syndrome （SS）， a disorder of immune system， is one of the dominant diseases treated by traditional Chinese medicine （TCM）. China Association of Chinese Medicine organized experts in the field of TCM and western medicine rheumatology and pharmacology to discuss the advantages and optimal regimens of TCM for the treatment of SS. The experts generally agreed on the low early diagnosis rate of SS and the lack of targeted therapeutic drugs. In addition， autoimmune abnormality is the key factor in the occurrence of SS and deficiency of both Qi and Yin is the core pathogenesis. SS has unique tongue manifestations， which is expected to allow for the early diagnosis and treatment with integrated traditional Chinese and western medicine. TCM has advantages in treating SS in terms of alleviating clinical symptoms and systemic involvement， individualized treatment， relieving sleep and mood disorders， preventing the occurrence in the early stage， and enhancing the effectiveness and reducing toxicity in the treatment by integrated TCM and western medicine. In general， TCM has advantages in different stages of SS. Internal and external use of TCM， acupuncture， and acupotome are all available options. The optimal regimens should be determined on the basis of pattern identification， stage of disease， and the advantages of TCM. Clinical characteristics and biomarkers of SS should be studied to classify patients， so as to design precision evidence-based TCM regimens for SS. On the basis of unique tongue manifestations of SS， models for early diagnosis and poor prognosis identification of SS should also be established to achieve early prevention and treatment and to improve the prognosis. In the future， we should vigorously carry out high-quality evidence-based medical research on the treatment of SS by TCM and integrated traditional Chinese and western medicine and develop relevant guidelines to optimize and standardize current diagnosis and treatment， thereby laying a basis for clarifying and explaining the advantages of TCM in treating SS.

Traditional Chinese Medicine Syndrome of Primary Sjögren's Syndrome Patients with Interstitial Lung Disease / 中国实验方剂学杂志

ObjectiveTo summarize the characteristics of traditional Chinese medicine （TCM） syndrome in primary Sjögren's syndrome （pSS） patients with interstitial lung disease （ILD） and to explore associated factors. MethodA survey was conducted and pSS patients who were treated in TCM department of rheumatism at China-Japan Friendship Hospital from December 2018 to April 2022 were included. Tongue manifestations and syndromes of patients were recorded. pSS patients with ILD were classified into the pSS-ILD group and those without the ILD were included in the pSS-non-ILD group. The tongue manifestations， syndromes， and laboratory indexes were compared between the two groups， and logistic regression was used to explore the factors associated with pSS-ILD. ResultA total of 200 pSS patients were included， with 186 （93.0%） females， median age of 57 years， and median disease course of 60 months， of which 44 （22%） had pSS-ILD. In terms of tongue manifestations， pSS-ILD patients generally had dark/purple/stasis tongue， fissured tongue， and tongue with little fluid， thick coating， yellow coating， and greasy coating. The proportion patients with yellow coating was higher in pSS-ILD group than in the pSS-non-ILD group （χ2=4.799，P<0.05）. In terms of syndrome， more than 40% of pSS-ILD patients had Qi deficiency， Yin deficiency， phlegm-dampness， Qi stagnation， and/or blood stasis syndrome. As for Yin deficiency， liver-kidney Yin deficiency syndrome ranked the first. For Qi deficiency， lung Qi deficiency syndrome was most commonly seen. The proportion of patients with lung Qi deficiency was higher in the pSS-ILD group than in the pSS-non-ILD group （χ2=18.667，P<0.01）. As to laboratory indexes， compared with the pSS-non-ILD group， pSS-ILD group had high proportion of anti-SSA-positive patients （P<0.05） and high levels of C-reactive protein （CRP） （P<0.01）， complement C3 （χ2=4.332，P<0.05）， and complement C4 （P<0.05）. Logistic regression analysis showed that pSS with ILD was positively associated with lung Qi deficiency ［odds ratio （OR）=6.079， 95% confidence interval （CI） 2.585-14.298， P<0.01）］ and yellow coating （OR=5.260， 95% CI 1.337-20.692， P<0.05） and negatively associated with low C4 （OR=0.199， 95% CI 0.070-0.564， P<0.01）. ConclusionAbout 22% of pSS patients had ILD， and patients with pSS-ILD generally have Qi deficiency， Yin deficiency， phlegm-dampness， Qi stagnation， and/or blood stasis syndrome. Yellow coating， lung Qi deficiency and C4 level are factors associated with pSS combined with ILD.

Clinical Characteristics of Geographic Tongue in Patients with Primary Sjögren's Syndrome / 中国实验方剂学杂志

ObjectiveTo analyze the clinical characteristics of geographic tongue in patients with primary Sjögren's syndrome （pSS）. MethodPatients with pSS treated in the China-Japan Friendship Hospital from December 2018 to October 2021 were enrolled and divided into different groups according to the presence of geographic tongue or the severity. Phi correlation analysis，Chi-square test， and Mann-Whitney test were used to analyze the clinical characteristics of patients with geographic tongue. ResultA total of 182 pSS patients were included in this study，including 75 （41.2%） patients with geographic tongue and 107 （58.8%） without geographic tongue. Partial exfoliation was more common than total exfoliation， and the anterior part of the tongue was the most common exfoliation site. The number of patients with severe geographic tongue was more than those with mild-to-moderate geographic tongue. Compared with pSS patients without geographic tongue，those with geographic tongue were more common in fissured tongue （92.0%/41.1%，χ2=48.491，P<0.05），red or crimson tongue （48.0%/23.3%，χ2=12.009，P<0.05），Yin deficiency syndrome （100.0%/43.9%，χ2=62.739，P<0.05），and Qi deficiency syndrome （94.7%∶50.5%，χ2=40.046，P<0.05），less common in phlegm-dampness syndrome （33.3%/72.0%，χ2=26.709，P<0.05），and showed higher proportions in hyperglobulinemia （89.3%/65.4%，χ2=13.547，P<0.01），ANA ≥1∶160 （78.1%/57.3%，χ2=8.227，P<0.01），and positive RF （51.4%/36.5%，χ2=3.877，P<0.05）. Compared with pSS patients with mild geographic tongue，pSS patients with moderate-to-severe geographic tongue had higher proportions in hyperglobulinemia （98.1%/68.2%，χ2=14.617，P<0.01），positive anti-CENP-B （26.0%/4.8%，χ2=4.214，P<0.05），and reduced complement 3 （26.4%/4.5%，χ2=4.647，P<0.05）. The geographic tongue was positively associated with fissured tongue （φ=0.531），Yin deficiency syndrome （φ=0.587），and Qi deficiency syndrome （φ=0.469），negatively associated with phlegm-dampness syndrome （φ=-0.447），and weakly associated with tongue color （φ<0.4）. There was no statistical difference in the disease activity index between patients with or without geographic tongue and severity. ConclusionMore than 40% of pSS patients had geographic tongue accompanied by fissured tongue. Geographic tongue is positively associated with Yin deficiency syndrome and Qi deficiency syndrome，and negatively associated with phlegm-dampness syndrome， indicating that treatment should be based on tonifying Qi and nourishing Yin. Compared with pSS patients without geographic tongue， those with geographic tongue may have higher positive rate of some immune indicators，which deserves further exploration.

Characteristics of Tongue Manifestations and Syndromes of Patients with Primary Sjögren's Syndrome of Different Time / 中国实验方剂学杂志

ObjectiveTo explore the characteristics of tongue manifestations and traditional Chinese medicine （TCM） syndromes in patients with primary Sjogren's syndrome （pSS） of different time. MethodpSS patients who visited TCM Department of Rheumatism in China-Japan Friendship Hospital from December 2018 to October 2021 were included and grouped according to the disease courses （short<5 years， medium 5-10 years， long > 10 years）. Chi-square test was used for comparison between three groups and Bonferroni method for multiple comparisons. In the pairwise comparison， P<0.017 indicated significant difference. Chi-square test was performed on the syndrome and specific tongue manifestations with inter-group differences to analyze the trend of tongue manifestations and TCM syndromes over time （interval： two years）. ResultA total of 193 pSS patients were enrolled， with 85 （44.0%） of short disease course， 69 （35.8%） of medium disease course， and 39 （20.2%） of long disease course. The common tongue manifestations were crimson tongue， fissured tongue， thin tongue， lack of fluid， and dry coating， which showed no significant difference among the three groups. Higher proportion of patients with light red tongue was observed in the group with short disease course than in group with medium disease course （χ2=6.407， P<0.017）. Higher proportions of patients with thick coating （χ2=6.784， P<0.017） and phlegm-dampness syndrome （χ2=11.545， P<0.017） and lower proportion of patients with Qi deficiency syndrome （χ2=12.706， P<0.017） were found in the group with short disease course than in the group with long disease course. Patients with medium （χ2=6.358， P<0.017） and long （χ2=8.279， P<0.017） disease course tended to have exfoliated coating compared with those with short disease course， and the proportion of patients with exfoliated coating rose and the proportion of patients with thick greasy coating decreased over time （Ptrend<0.05）. In addition， the proportion of patients with phlegm-dampness syndrome decreased and that with Qi deficiency syndrome increased over time （Ptrend<0.05）. ConclusionIn the early stage， patients with pSS often show both dryness and dampness， as manifested by the thick greasy coating and phlegm-dampness syndrome. In the medium and late stage， patients often have Qi-Yin deficiency， as evidenced by exfoliated coating and Qi deficiency. In the clinical practice， medicines should be prescribed based on tongue manifestations and TCM syndrome of patients.

Effect of Huashi Runzao Prescription on Primary Sjögren's Syndrome / 中国实验方剂学杂志

ObjectiveTo observe the efficacy and safety of Huashi Runzao prescription for patients with primary Sjögren's syndrome （pSS） of combined dryness and dampness pattern. MethodA total of 105 eligible patients were randomized into the experimental group （65 cases） and control group （40 cases）， and they were respectively treated with Huashi Runzao prescription and hydroxychloroquine for 12 weeks. Visual Analogue Scale （VAS） was employed to assess the symptoms. The symptoms of dryness， fatigue， and pain， European League Against Rheumatism （EULAR） Sjögren's Syndrome Patient Reported Index （ESSPRI）， EULAR Sjögren's syndrome disease activity index （ESSDAI）， and immune inflammatory indicators before and after treatment were compared between the two groups， and adverse reactions were observed. ResultAfter treatment， the ESSPRI score was lower than that before treatment in the experimental groups （P<0.01） and was lower in the experimental group than in the control group （P<0.05）. The VAS scores of dry mouth， dry eyes， overall dryness， fatigue， and pain in the experimental group decreased compared with those before treatment （P<0.01）， and the experimental group had lower VAS scores of dry mouth and overall dryness than the control group （P<0.01）. After treatment， the ESSDAI score of both groups decreased compared with that before treatment （P<0.05， P<0.01）， but there was no significant difference between the groups. After treatment， the level of immunoglobulin M （IgM） decreased （P<0.01） and the level of complement C3 increased （P<0.01） in the experimental group， while the level of complement C3 decreased in the control group （P<0.05）. There was no significant difference in the laboratory indexes between groups. During the treatment， stomachache occurred to one case in the experimental group， which was alleviated after the treatment， and no adverse reaction was observed in the control group. According to the chi-square test， the occurrence of adverse reactions was insignificantly different between the two groups. ConclusionHuashi Runzao prescription can alleviate the symptoms of dryness， fatigue， and pain， and reduce disease activity without associated side effects in pSS patients with combined dampness and dryness pattern.

Effect of Huashi Runzao Prescription on Structure and Function of Submandibular Gland in Sjögren's Syndrome Model Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Huashi Runzao prescription （HRP） on the histopathological injury and function of submandibular gland in naive non-obese diabetic （NOD/Ltj） mouse model of Sjögren's syndrome （SS） and its regulatory effect on aquaporin 5 （AQP5） expression in submandibular gland cells. MethodThe SS model was induced in NOD/Ltj mice. The NOD/Ltj female mice aged nine weeks were selected and randomly assigned into model group，HRP group （7.15 g·kg-1·d-1），and hydroxychloroquine （HCQ） group （1.30 g·kg-1·d-1）， and female BALB/c mice in the same age were selected and assigned into the normal group， with six mice in each group. Drug intervention lasted eight weeks. The water consumption and salivary flow rate （SFR） of each group were recorded. The pathological staining results of the submandibular gland of mice in each group were observed and scored. AQP5 expression was determined by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed increased water consumption （P<0.05） and reduced SFR （P<0.05）. Compared with the model group， the HRP group showed decreased water consumption （P<0.05） and increased SFR （P<0.05）， and the HCQ group showed increased SFR （P<0.05）. In terms of histopathological results of the submandibular gland，compared with the normal group，the model group showed increased pathological score， number of lymphocyte infiltration foci，and percentage of lymphatic infiltration area （P<0.05）. Compared with the model group， the HRP group showed reduced pathological scores and number of lymphocyte infiltration foci （P<0.05）， and the HRP group and the HCQ group showed reduced percentage of lymphatic infiltration area（P<0.05）. The results of IHC and Western blot showed that compared with the normal group，the model group showed down-regulated expression level of AQP5 protein （P<0.05）， and compared with the model group and the HCQ group，the HRP group showed up-regulated expression level of AQP5 protein （P<0.05）. ConclusionHRP can improve the secretion function of submandibular gland acinous cells and glandular structure injury in SS model mice， and its mechanism may be related to the up-regulation of AQP5 protein expression level in submandibular gland cells.

Analysis of factors related to hemocytopenia and interstitial lung disease secondary to primary Sj?gren's syndrome / 中华风湿病学杂志

Objective:To detect the factors related to hemocytopenia and interstitial lung disease (ILD) secondary to primary Sj?gren's syndrome (pSS) in in-patients.Methods:Clinical characteristics of patients with pSS hospitalized in China-Japan Friendship Hospital from March 2014 to October 2020 were retrospectively analyzed. Patients were divided into different groups according to hemocytopenia and ILD. Chi-square test and Mann-Whitney U test were used to compare data in subgroups, and logistic regression were used to detect factors related to hemocytopenia and ILD secondary to pSS. Results:Five hundred and seventy-one inpatients with pSS were included in this study and the female: male ratio was 8∶1. Two hundred and seventy five of included patients had hemocytopenia (48.2%) and 180 patients had ILD (31.5%). Compared with patients without hemocytopenia, patients with hemocytopenia had higher ratio in low C3 [ OR=2.326, 95% CI(1.483, 3.650), P<0.01] and elevation of erythrocyte sedimentation rate (ESR) [ OR=1.912, 95% CI(1.233, 2.964), PP<0.01) . Compared with patients without ILD, patients with ILD showed higher ratio in male[ OR=2.509, 95% CI(1.269, 4.959), P<0.01) and fatigue [ OR=5.190, 95% CI(5.190, 13.931), P<0.01) , lower positive rate of anti-SSA antibody [ OR=0.392, 95% CI(0.230, 0.668), P<0.01) and anti-CENPB [ OR=0.337, 95% CI(0.145, 0.782), P<0.01] antibodies, and lower ratio in low C3[ OR=0.332, 95% CI(0.189, 0.582), P<0.01]. Conclusion:Low C3 and high ESR may be risk factors for developing hemocytopenia in patients with pSS. Men with pSS may be susceptible to ILD, while pSS patients with ILD may have lower ratio in positive anti-SSA antibody, positive anti-CENPB antibody and low C3. All of these findings are yet to be validated by future prospective cohort studies.

Difference in clinical characteristics of patients with primary Sj?gren's syndrome by gender and age of disease onset / 中华风湿病学杂志

Objective:To compare the clinical characteristics of patients with primary Sj?gren's syndrome (pSS) by gender and age of disease onset.Methods:Clinical data of hospitalized patients with pSS in China-Japan Friendship Hospital from March 2014 to August 2020 were retrospectively analyzed. Patients were divided into different groups according to their genders and ages of disease onset (young grong <30 years, middle-age group 30-59 years, elderly group ≥60 years). Chi-square test and Mann-Whitney U test were used to compare data in subgroups, and logistic regression was performed to analyze data after control covariates. Results:Five hundred and forty one patients with pSS were included in this study and 481 of them were women (88.9%) Women had higher ratio than men in dry mouth [ OR (95% CI) =2.172(1.091, 4.323), P=0.027], dry eyes [ OR(95% CI)=2.179(1.062, 4.469), P=0.034], leukocytopenia [ OR(95% CI)=3.789(1.150, 12.482), P=0.029], ANA titer≥1∶160 [ OR(95% CI)=2.233(1.279, 3.898), P<0.01], positive anti-SSA [ OR(95% CI)=2.919(1.644, 5.183), P<0.01], positive anti-Ro52 [ OR(95% CI)=3.018(1.685, 5.405), P<0.01], while men had higher ratio than women in parotid enlargement [ OR(95% CI)=2.345(1.281, 4.325), P<0.01], and interstitial lung disease (ILD) [ OR(95% CI)=2.593(1.460, 4.606), P<0.01]. Compared with patients in young group, patients in middles age group had higher ratio in dental caries [ OR(95% CI)=5.940(2.230, 15.819), P<0.01], xero-phthalmia [ OR(95% CI)=2.904(1.313, 6.425), P<0.01], arthralgia [ OR(95% CI)=1.959(1.039, 3.694), P=0.038] and ILD [ OR(95% CI)=2.247(1.018, 4.959), P=0.045], but lower ratio in renal involvement [ OR(95% CI)=0.402(0.211, 0.766), P<0.01]; patients in elderly group had higher ratio in dental caries [ OR(95% CI)=7.437(2.441, 22.656), P<0.01], xerophthalmia [ OR(95% CI)=6.084(1.901, 19.468), P<0.01], and ILD [ OR(95% CI)=4.857(2.029,11.627), P<0.01]. Compared with patients in elderly group, patients in young group had higher positive rate in anti-SSA [ OR(95% CI)=2.836(1.245, 6.459), P=0.013], anti-SSB [ OR(95% CI)=3.075(1.413, 6.690), P<0.01], rheumatoid factors (RF) [ OR(95% CI)=3.323(1.620, 6.817), P<0.01] and elevated immunoglobulin G (IgG)[ OR(95% CI)=3.567(1.747, 7.284), P<0.01]; patients in middle age group had higher positive rate in anti-SSB[ OR(95% CI)=2.330(1.315, 4.130), P<0.01], RF [ OR(95% CI)=2.026(1.279, 3.208), P<0.01], and elevated IgG [ OR(95% CI)=2.077(1.297, 3.327), P<0.01]. Conclusion:Women with pSS present a higher ratio in dry mouth, dry eyes, leukocytopenia and positive autoantibodies than men, while parotid enlargement and ILD are more common in men than women. Young patients are prone to renal involvement, middle-aged patients are prone to arthralgia, while elderly patients are prone to dental caries and xerophthalmia. With the growth of age, the positive rates of autoantibodies and elevated IgG are decreased gradually in patients with pSS, but the ratios of dental caries, xerophthalmia and ILD is increased gradually.

Application of problem-based learning method in the internal medical teaching of TCM / 国际中医中药杂志

Objective To explore the effect of problem-based learning method in traditional Chinese internal medicine teaching. Methods 58 students enrolled in the major of integrated traditional Chinese and western medicine in class C at the Beijing University of Chinese medicine were arranged to receive PBL(test group)or traditional teaching methods(control group)in 2 courses and complete 116 questionnaires. The teaching outcomes were evaluated by questionnaire and individual interviews. Results Compared with controls,students receiving PBL performed significantly better in terms of active classroom atmosphere, broadening their knowledge, and improving teamwork ability(χ2 were 7.16, 4.07, 4.09, P<0.05). Conclusion The PBL strategy has the advantage than the traditional teaching methods in traditional Chinese internal medicine teaching.

Research of integrative medicine therapy for severe systemic lupus erythematosus from medical history analysis / 国际中医中药杂志

Objective To ivestigate integrative medicine therapy for severe systemic lupus erythematosus.Methods In 2005,we successfully salvaged a severe SLE patient,who was an inpatient from the TCM Rheumatology department of China-Japan relationship hospital.The mainly clinic manifestations included severe pulmonary hypertension,gangrene and pancytopenia.We analyzed this ease.Results By integrative medicine therapy,we successfully salvaged this patient.Conclusion The key points for integrative medicine therapy for severe systemic lupus erythematosus included:1.Using strong measures to control the disease progress,including hormones,immunosuppressive agents; 2.Positive and effective symptomatic treatment aiming at pulmonary hypertension and severe gangrene; 3.Emphasizing the effect of Chinese medicine,using integrative medicine therapy.In sum,in this case,we applied integrative medicine therapy and got very perfect clinic effect at last.