ObjectiveTo explore the correlation between the occurrence of cardiovascular events in rheumatoid arthritis（RA） and traditional Chinese medicine（TCM） syndrome. MethodsThe cross-sectional study selected 6713 RA patients from 122 centres nationwide， in which general information such as name， gender， age， height， body weight， and course of disease were collected by completing a questionnaire； patients were classified into eight types of syndrome according to the information of their four examinations，i.e. wind-dampness obstruction syndrome， cold-dampness obstruction syndrome， dampness-heat obstruction syndrome， phlegm-stasis obstruction syndrome， stasis-blood obstructing collateral syndrome， qi-blood deficiency syndrome， liver-kidney insufficiency syndrome， and qi-yin deficiency syndrome. According to the occurrence of cardiovascular events， they were divided into the occurrence group and the non-occurrence group， and the condition assessment data and laboratory examination indexes were recorded. The test of difference between groups was used to analyse the possible risk factors for the occurrence of RA cardiovascular events， and binary logistic regression was used to analyse the correlation between TCM syndromes and RA cardiovascular events. ResultsA total of 6713 RA patients were included， including 256 cases in occurrence group and 6457 in non-occurrence group. There was no statistically significant difference between groups in terms of height， gender， insomnia， appetite， white blood cell（WBC）， hemoglobin（HGB）， platelets（PLT）， rheumatoid factor（RF）， anti-cyclic peptide containing citrulline（CCP）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， γ-glutamyl transpeptidase（GGT）， urea creatinine（CREA）， and glucose（GLU）（P＞0.05）. The TCM syndromes between groups showed significant statistic differences（P＜0.05）. Patients in occurrence group had longer disease duration， heavier body weight， and older age； more severe conditions such as disease activity（DAS-28）， number of painful joints（TJC）， number of swollen joints（SJC）， health questionnaire scores（HAQ）， visual analog scores（VAS）， restlessness， and fatigue； higher blood sedimentation rate（ESR）， low-density lipoprotein（LDL-C）， triglyceride（TG）， total cholesterol（TC）， D-Dimer， and lower high-density lipoprotein（HDL-C）（P＜0.05）. The distribution of syndrome types showed that dampness-heat obstruction syndrome accounted for the largest proportion of patients in both groups and was higher in RA cardiovascular events. Logistic regression analysis showed that the occurrence of RA cardiovascular events was strongly associated with dampness-heat obstruction syndrome［OR=5.937， 95%CI （4.434， 7.949）， P＜0.001］. ConclusionThe occurrence of RA cardiovascular events were associated with TCM syndromes， and the probability of cardiovascular events in the RA patients with dampness-heat obstruction syndrome was 5.937 times higher than patients with other TCM syndromes.

OBJECTIVE: To identify the CDYL-interacting proteins in murine testis and investigate the mechanism of CDYL involved in spermatogenesis. METHODS: CDYL-interacting partners in testis were identified using co-immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Expression pattern of CDYL-interacting protein MYH9 was analyzed through immunohistochemistry (IHC), confocal immunofluorescence (IF) and Western blot (WB) in mouse testicular cells. The effect of the Cdyl conditional knockout (CdylcKO) in spermatogenic cell on Myh9 expression was quantified via RT-qPCR, WB and IF imaging in both spermatids and spermatozoa from cauda epididymides. RESULTS: Direct interaction between MYH9 and CDYL was confirmed in murine testis. During spermiogenesis, MYH9 exhibited co-localization with CDYL at the manchette structure, and binding to F-ACTIN, the component of manchette. In cauda epididymal spermatozoa, MYH9 signal concentrated on acrosomal region and continuously distributed along the tail length. Conditional deletion of Cdyl in spermatogenic cell resulted in the transcriptional downregulation of Myh9. In spermatids, CdylcKO led to reduced but retained MYH9 localization to the disorganized manchette structure. In spermatozoa from CdylcKO mice, abnormalities of MYH9 localization were observed, including attenuation of acrosomal signal and/or partial vanishment/enhancement of tail signal. CONCLUSION In murine spermatids, MYH9 protein is localized to the manchette structure, with its expression and subcellular distribution is affected by CDYL protein. CDYL-MYH9 interaction is essential for the spermiogenesis.
Animals ; Male ; Mice ; Testis/metabolism* ; Myosin Heavy Chains/metabolism* ; Spermatogenesis ; Mice, Knockout

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

Systemic lupus erythematosus （SLE） may lead to secondary gynecological and obstetric disorders such as decreased ovarian reserve function， menstrual abnormalities， and adverse pregnancy outcomes. Based on "bi （痹） of both body and viscera" theory， this paper proposed that the core mechanism of SLE secondary gynecological and obstetric diseases lies in the mutual transformation between "body bi" and "viscera bi"， which together affect the uterus. Physiologically， uterus forms an internal-external network with the body and viscera through the meridians and blood vessels. Pathologically， when the healthy qi is deficient， nourishment of the body and viscera is impaired； when toxins and stasis accumulate， pathogenic factors disturb the uterus through the chong （冲） and ren （任） meri-dians. The resulting obstruction in the uterus can， in turn， manifest externally and aggravate damage to the body and viscera. Therefore， the pathogenesis of SLE secondary gynecological and obstetric diseases follows a dynamic trajectory of "body bi first， body bi affecting viscera， and then bi of both body and viscera". In treatment， the principle of harmonizing and balancing the healthy qi is emphasized. The main approach is to regulate the viscera， stabilize the body， and nourish the uterus， with the coordination of nourishing the viscera through the body， thereby achieving simultaneous treatment of both body and viscera. This highlights the guiding significance of the "bi of both body and viscera" theory in preventing and treating SLE secondary gynecological and obstetric diseases.

ObjectiveTo investigate the syndrome evolution patterns， characteristics of the used herbal medicinals， and efficacy variations across different stages of rheumatoid arthritis （RA） progression. MethodsBased on the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine （CERTAIN）， 2,506 RA patients were retrospectively enrolled and categorized into ＜6 months group （166 cases）， 6 months to ＜5 years group （1063 cases）， 5 to ＜20 years group （1067 cases）， and ≥20 years group （210 cases）. Syndromes were differentiated before and after traditional Chinese medicine （TCM） treatment， including damp-heat obstruction， wind-damp obstruction， cold-damp obstruction， blood stasis obstructed in the collaterals， phlegm-stasis obstruction， liver-kidney insufficiency， qi and blood deficiency， and qi-yin deficiency. The syndrome evolution rate was calculated for high-frequency syndromes before and after treatment. Analysis was conducted on top 20 frequently used Chinese herbs at the first diagnosis. Clinical efficacy of the 28-joint disease activity score based on erythrocyte sedimentation rate （DAS28-ESR） and 28-joint disease activity score based on C-reactive protein （DAS28-CRP） before and after treatment were assessed. A multivariate logistic regression analysis was performed to identify factors affecting the efficacy of TCM treatment. ResultsPatients with course of disease shorter than 6 months predominantly presented with cold-dampness obstruction syndrome （49/166， 29.5%）， wind-dampness obstruction syndrome （46/166， 27.7%）， and dampness-heat obstruction syndrome （43/166， 25.9%）. For patients with course of disease logner than 6 months and shorter than 5 years and those within 5 to 20 years， the dominant syndrome was dampness-heat obstruction syndrome （324/1063， 30.5% and 318/1067， 29.8%， respectively）. In patients with disease duration ≥20 years， liver-kidney insufficiency syndrome and dampness-heat obstruction syndrome both predominated， each accounting for 25.24% （53/210）. The syndromes with more than 100 cases before treatment and a syndrome evolution rate greater than 10% after treatment were dampness-heat obstruction （201/738， 27.2%）， liver-kidney insufficiency （119/367， 32.4%）， and phlegm-stasis obstruction syndromes （73/172， 42.4%）. These were classified as high-frequency syndromes. After treatment， damp-heat obstruction syndrome and liver-kidney insufficiency syndrome primarily evolved into wind-damp obstruction syndrome， while phlegm-stasis obstruction syndrome evolved into damp-heat obstruction and cold-damp obstruction syndrome. The top two commonly used Chinese herbs across all groups were Gancao （Radix et Rhizoma Glycyrrhizae） and Baishao （Radix Paeoniae Alba）. In the ＜6 months group and the 6 months to ＜5 years group， high-frequency herbs also included Fangfeng （Radix Saposhnikoviae）， Duhuo （Radix Angelicae Pubescentis）， Chuanxiong （Rhizoma Chuanxiong）， and Qianghuo （Radix et Rhizoma Notopterygii）. In the 5 to ＜20 years group and the ≥20 years group， the usage of Huangqi （Radix Astragali）， Fuling （Poria）， Niuxi （Radix Achyranthis Bidentatae）， and Danggui （Radix Angelicae Sinensis） increased， while the proportion of Fangfeng and Duhuo decreased. After treatment， the DAS28-ESR and DAS28-CRP scores in all groups significantly decreased （P＜0.05）. There were statistically significant differences in clinical efficacy based on DAS28-ESR and DAS28-CRP across all groups （P＜0.01）. Multivariate logistic regression revealed significantly reduced treatment efficacy in the 6 months-5 years group （OR=0.4）， 5~20 years group （OR=0.5）， and ≥20 years group （OR=0.4） compared to the ＜6 months group. ConclusionRA syndromes follow a progression pattern from excess to deficiency， with corresponding transition in herbal usage from pathogen-eliminating to healthy qi-reinforcing approaches. TCM intervention can significantly reduce disease activity of RA， with superior efficacy in patients with disease duration shorter than 6 months.

ObjectiveTo evaluate the clinical efficacy and safety of Tripterygium wilfordii polyglycoside tablets （TWP） in the treatment of rheumatoid arthritis （RA） in the real world. MethodDiagnosis and treatment data of patients with RA in Chinese medicine rheumatology registration research information platform information database （CERTAIN） from January 1，2019 to January， 2024 were collected. According to the inclusion and exclusion criteria， data were screened. The included data were divided into an exposure group and a control group according to the use of TWP or not. Propensity score matching （PSM） was used in both groups to keep the baseline balanced and comparable. The disease activity score （DAS28-ESR） of 28 joints based on the erythrocyte sedimentation rate （ESR）before and after treatment was compared between the two groups， as well as health assessment questionnaire （HAQ），visual analogue scale （VAS），tender joint count （TJC），swollen joint count （SJC）， patient's global assessment （PGA），evaluator's global assessment （EGA），laboratory indexes， clinical curative effect， and adverse reactions. ResultA total of 3 978 patients were included，including 929 in the exposure group and 3 049 in the control group. Before PSM，there were significant differences in demographic information，DAS28-ESR score，PGA，EGA，HAQ，VAS scores，SJC， and TJC between the two groups （P<0.05）. After successful PSM matching，922 patients in the exposure group and 922 patients in the control group were included. There was no significant difference in demographic information and DAS28-ESR between the two groups before treatment，and the differences in other indexes between the two groups decreased to varying degrees. After treatment，the DAS28-ESR，PGA，EGA，HAQ，SJC，TJC，VAS scores， ESR，and IgG immune index of the two groups were significantly lower （P<0.01）. Compared with those in the control group after treatment，the DAS28-ESR，PGA，EGA，HAQ，VAS scores， and ESR in the exposure group after treatment decreased more significantly （P<0.05，P<0.01）. There was no significant difference in TJC in the exposure group after treatment. However， TJC in the exposure group was significantly higher than that in the control group before treatment （P<0.05）. In terms of TJC reduction，the exposure group performed better than the control group. There was no significant difference in SJC and IgG between the exposure group and the control group after treatment. After treatment，the clinical symptoms of poor appetite，insomnia and many dreams，upset，fatigue，and fear of wind and cold in the two groups were improved. Except that the proportion of women in the exposure group was higher than that in the control group （P<0.01），there was no significant difference in the incidence of other adverse reactions between the two groups after treatment. ConclusionTWP to treat RA can effectively reduce DAS28-ESR，PGA，EGA，HAQ，TJC，and VAS scores and improve the general symptoms. Except for the women at childbearing age with fertility requirements that TWP is not applicable，it shows good security.

Objective To investigate the clinical efficacy of percutaneous closure of foramen ovale guided by transthoracic echocardio-graphy with simply delivery sheath.Methods The clinical data of patients with patent foramen ovale underwent interventional closure and percutaneous closure guided by transthoracic echocardiography with simply delivery sheath in our hospital from January 2020 to December 2022 were analyzed retrospectively,the patients were divided into interventional closure group(40 cases)and simply delivery sheath group(39 cases).The operation time,incidence of surgical complications,and surgical success rates of patients in the two groups were compared.The closure effect were evaluated by ultrasound immediately after surgery.All the patients were followed up for 6 months after surgery to evaluate remission of the symptoms.Results The surgical success rate of simply delivery sheath group(100%)was higher than that of interventional closure group(90.0%),with statistically significant difference(P<0.05).The operation time of simply delivery sheath group was longer than that of interventional closure group,with statistically significant difference(P<0.05).One patient in the interventional closure group had small amount of pericardial effusion during the operation.Two patients had decreased blood pressure and slowed heart rate in simply delivery sheath group,and symptoms disappeared after treatment.There was no significant difference in the incidence of complications between the two groups(P>0.05).After 6-month follow-up,all occluders were in good position and no residual leakage was found.The symptoms of headache or dizziness disappeared in 28 patients in interventional closure group,significantly relieved in 8 patients;the symptoms of headache or dizziness disappeared in 30 patients in simply delivery sheath group,and significantly relieved in 9 patients.Conclusion Percutaneous closure for patent foramen ovale under the guidence of transthoracic echocardiography with simply delivery sheath is safe and feasible with satisfactory efficacy and higher successful rate without radiation hazard.It is worthy of clinical promotion.

Based on the previous publications， it is believed that damp-heat syndrome is the core syndrome of rheumatoid arthritis （RA）， and Qingre Huoxue Formula （清热活血方） is an effective formula for the treatment of damp-heat syndrome of RA. “Inflammation-bone destruction” is a key pathological link of RA， and it is also the advantage of the effectiveness of Qingre Huoxue Formula. Leucine rich α-2-glycoprotein 1 （LRG1） can mediate the transforming growth factor-β （TGF-β） signalling pathway to participate in the pathogenic process of “inflammation-bone destruction” of RA， and it can be used as a target protein in the treatment of damp-heat syndrome of RA by Qingre Huoxue Formula. Accordingly， a scientific hypothesis was proposed that Qingre Huoxue Formula may regulate TGF-β signalling pathway mediated by LRG1 to improve “inflammation-bone destruction” of RA， and it was envisioned that the clinical effect of Qingre Huoxue Formula on LRG1 could be confirmed through clinical studies， and the mechanism of action of Qingre Huoxue Formula on the LRG1/TGF-β signalling axis as well as the influence of the expression or non-expression of the LRG1/TGF-β signalling axis on the therapeutic effectiveness of Qingre Huoxue Formula could be clarified through animal experiments.

Objective:To investigate the application effect of population/patient, intervention/exposure, comparison/control, and outcome (PICO) principles based on evidence-based medicine in case reports of residents in operative dentistry and endodontics.Methods:A total of 56 residents in Department of Conservative Dentistry and Endodontics in Hospital of Stomatology, Sun Yat-sen University, were selected and randomly divided into experimental group and control group, with 28 residents in each group. The residents in the experimental group were guided by the teachers to apply PICO principles in preparing case reports, and those in the control group were guided by the teachers to prepare traditional case reports. The two groups were compared in terms of the language expression of case reports, the completeness of case records, the rationality and advancement of the diagnosis and treatment regimen, and the logicality and scientificity of discussion, and a questionnaire survey was performed for both groups. SPSS 24.0 software was used to perform the descriptive statistical analysis, the t-test, and the chi-square test. Results:The experimental group had a significantly higher mean score of case report than the control group in department examination [(89.25±3.24) vs. (86.32±3.55), t=3.23, P=0.002], especially the score of the logicality and scientificity of discussion [(27.25±0.16) vs. (23.78±0.36), t=8.77, P<0.001]. The questionnaire survey showed that the experimental group had a significant increase in the frequency of participating in case reports ( P=0.035). Conclusions:The application of PICO principles can enhance the overall quality of case reports by residents and improve their enthusiasm in participating in case reports in department of operative dentistry and endodontics.

Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.