This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

Objective To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus(SLE)and lupus nephritis(LN)in children,as well as their diagnostic value for active SLE and LN.Methods A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital,Central South University from January 2016 to March 2019 as the SLE group,all of whom were tested for anti-C1q antibodies.A control group was formed by collecting 70 hospitalized children with other autoimmune diseases(OAD)during the same period.The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed,and the diagnostic value of anti-C1q in SLE and LN was evaluated.Results The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group(P<0.05).The SLE disease activity index score was positively correlated with anti-C1q antibodies(rs=0.371,P<0.001)and positively correlated with anti-double-stranded DNA antibodies(rs=0.370,P<0.001).The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90%and 53.90%,respectively,with an area under the curve of 0.720(P<0.05)and a critical value of 5.45 U/mL.The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50%and 85.00%,respectively,with an area under the curve of 0.675(P<0.05)and a critical value of 22.05 U/mL.Conclusions Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.

Objective To explore the etiology and pathogenesis of dry eye by studying the distribution pattern of gender,age and traditional Chinese medicine(TCM)syndrome type in dry eye patients and by analyzing their correlation.Methods A total of 244 patients with dry eye who met the inclusion criteria were selected.The distribution of gender,age and TCM syndrome types was statistically analyzed,and then the correlation of TCM syndrome types with gender and age of dry eye patients was explored.Results(1)Of the 244 dry eye patients,96(39.34%)were male and 148(60.66%)were female,the incidence of the female being higher than that of the male.There were 124(50.82%)patients younger than 45 years old,81(33.20%)patients aged 45-60 years old,and 39(15.98%)patients older than 60 years old.The proportion of the patients younger than 45 years old was higher than that of other age groups.(2)Among the 244 patients with dry eyes,89 cases(36.47%)were differentiated as liver and kidney deficiency syndrome,75 cases(30.74%)were differentiated as qi stagnation and blood stasis syndrome,69 cases(28.28%)were differentiated as spleen and kidney deficiency,and 11 cases(4.51%)were differentiated as yin deficiency and damp-heat syndrome.And the occurrence frequency of the above four syndrome types was in descending order.(3)In the dry eye patients of various age groups,patients aged＜45 years old predominantly suffered from qistagnation and blood stasis syndrome,accounting for 41.94%(52/124);patients aged 45-60 years old and those aged＞60 years old predominantly suffered from liver and kidney deficiency syndrome,accounting for 46.91%(38/81)and 53.85%(21/39),respectively.The distribution of TCM syndrome types varied in the patients with different age groups,and the difference was statistically significant(χ2 = 22.128,P＜0.01).(4)In male dry eye patients,qi stagnation and blood stasis syndrome was predominant,accounting for 39.58%(38/96);among female dry eye patients,liver and kidney deficiency syndrome and spleen and kidney deficiency syndrome were prevalent,accounting for 41.89%(62/148)and 31.08%(46/148),respectively.The distribution of TCM syndrome types varied in the patients with different genders,and the difference was statistically significant(χ2 = 82.610,P＜0.01).Conclusion The TCM syndromes of patients with dry eyes are frequently differentiated as liver and kidney deficiency syndrome,followed by the qi stagnation and blood stasis syndrome.The prevalence of dry eyes is related to the gender and age,and gender and age are correlated with the TCM syndrome types to certain extent.

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.