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

The quality of moxa is a key factor affecting the efficacy of moxibustion. Traditional moxa grades are evaluated by the leaf-to-moxa ratio, but there is a lack of support from scientific data. Scanning electron microscopy(SEM), Image Pro Plus, Van Soest method, and stimultaneous thermal analysis(TGA/DSC) were used to characterize the scientific implication of the combustion differences between moxa with different leaf-to-moxa ratios(processed by crusher). The results showed that the median lengths from non-secretory trichomes(NSTs) of natural NSTs and moxa with leaf-to-moxa ratios of 3∶1, 5∶1, 10∶1, and 15∶1 were 542.46, 303.24, 291.18, 220.69, and 170.61 μm, respectively. The cellulose content of moxa increased significantly(P<0.05) with the increase in leaf-to-moxa ratio and the combustion parameters(T_i, t_i, D_i, C,-R_p,-R_v, S, D_b, and J_(total)) all showed an increasing trend. The correlation results showed that the burning properties of moxa(T_i,-R_v, t_i, and J_2) were significantly and positively correlated with cellulose content. NSTs with a length of 1-200 μm were significantly and positively correlated with J_2. NSTs with a length of 200-600 μm were significantly and positively correlated with J_1, T_(peak2), T_(peak1), and-R_v, and negatively correlated with J_(total), T_b, and t_b. As the leaf-to-moxa ratio increases, the NSTs in the moxa become shorter and the cellulose content increases, which is more conducive to ignition performance, heat release, and a milder, longer-lasting burn. The "NSTs-cellulose-TGA/DSC" quantitative evaluation method scientifically reveals the scientific connotation of the combustion of moxa with different leaf-to-moxa ratios and provides a scientific basis for the establishment of quality evaluation methods for moxa with different leaf-to-moxa ratios.
Trichomes ; Moxibustion ; Hot Temperature ; Plant Leaves

OBJECTIVE: To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis. METHODS: This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed. RESULTS: Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment. CONCLUSION BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).
Humans ; Gastrointestinal Microbiome ; Prospective Studies ; Liver Cirrhosis/drug therapy* ; Hepatitis B/drug therapy*

OBJECTIVE: To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests. METHODS: In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years. RESULTS: In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect. CONCLUSION Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.
Humans ; Diabetes Mellitus, Type 2/therapy* ; Self Efficacy ; Self-Management ; Blood Glucose Self-Monitoring ; Blood Glucose ; Self Care

Morinda officinalis oligosaccharides (MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan (5-HTP) → serotonin (5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan; meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation, and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide, as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.

Objective:To observe the effect of Yuxuebi tablets on hyperalgesia and foot swelling in mice with chronic inflammatory pain， and to explore the preliminary mechanism of action. Method:A mouse model of chronic inflammatory pain was established with left plantar injection of complete Freund's adjuvant （CFA）. The mice were divided into model group， positive drug ibuprofen group （91 mg·kg^-1）， Yuxuebi tablets low， medium and high dose groups （55， 110， 220 mg·kg^-1），with the sham operation group as the control. After successful modeling， the daily dose was divided into two doses in the morning and evening by gavage to give Yuxuebi tablets or ibuprofen to the stomach for a total of 19 days. On the 18^th day after the administration， the thermal pain threshold was detected by the hot plate method. On the 19^th day， the standard Von Frey fiber needle was used to detect the mechanical pain threshold of the mice， and the degree of foot swelling was scored and photographed. The liquid-phase suspension chip technology was used to quantitatively analyze 36 classic broad-spectrum inflammation-related factors like inflammatory factors and receptors. Bioinformatics were used to screen core targets and perform enzymelinked immunosorbent assay （ELISA） detection. Result:Compared with the sham operation group， the mechanical pain threshold and foot swelling score of the model froup significantly increased （P<0.01）， the latent time of heat sensitivity significantly decreased（P<0.01）， the expressions of 30 inflammatory factors in the foot increased（P<0.05）. Compared with the model group， the high dose of Yuxuebi tablets significantly reduced the mechanical pain threshold and foot swelling score of mice with chronic inflammatory pain（P<0.01）， significantly increased the latent time of heat sensitivity（P<0.05）， and reduced the expressions of 30 inflammatory factors in the foot（P<0.05）， among which tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and C-C chemokine ligand 2 （CCL2） were the core targets screened out， and the expressions of TNF-α， IL-17A， and CCL2 significantly decreased （P<0.01）. Conclusion:Yuxuebi tablets can relieve hyperalgesia and foot swelling in mice with chronic inflammatory pain， and its mechanism may be related to the inhibition of the expressions of peripheral inflammatory factors such as TNF-α， IL-17A， and CCL2 .

BACKGROUND: Resting heart rate (RHR) is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients. Bisoprolol fumarate, a second-generation beta-adrenoreceptor blockers (β-blocker) is commonly prescribed drug to manage hypertension. The present study was to retrospectively evaluate changes in the average RHR and its association with cardiovascular outcomes in bisoprolol-treated coronary artery disease (CAD) patients from the CAD treated with bisoprolol (BISO-CAD) study who had comorbid hypertension. METHODS: We performed ad-hoc analysis for hypertension sub-group of the BISO-CAD study (n = 866), which was a phase IV, multination, multi-center, single-arm, observational study carried out from October 2011 to July 2015 across China, South Korea, and Vietnam. Multivariate regression analysis was used to identify factors associated with incidence of composite cardiac clinical outcome (CCCO), the results were presented as adjusted odds ratio (OR) along with 95% confidence interval (CI) and adjusted P value. RESULTS: A total of 681 patients (mean age: 64.77 ± 10.33 years) with hypertension from BISO-CAD study were included in the analysis. Bisoprolol improved CCCOs in CAD patients with comorbid hypertension, with RHR <65 and <70 beats/min compared with RHR ≥65 and ≥75 beats/min, respectively, in the efficacy analysis (EA) set. In addition, it lowered RHR in both intent-to-treat (ITT) and EA groups after 6, 12, and 18 months of treatment. Further, RHR 70 to 74 beats/min resulted in significantly higher risk of CCCOs EA set of patients (adjusted OR: 4.34; 95% CI: 1.19-15.89; P = 0.03). Also, events of hospitalization due to acute coronary syndrome were higher when RHR 69 to 74 beats/min compared to RHR <69 beats/min in ITT patients. CONCLUSION Bisoprolol can effectively reduce RHR in Asian CAD patients with comorbid hypertension and hence, improve CCCO without affecting their blood pressure.

Objective To find a simple, sensitive and effective method to predict the occurrence of cogni-tive impairment in patients after a transient ischemic attack ( TIA) . Methods Thirty-six persons who had survived a first TIA and could walk independently were selected into a TIA group, with another 36 healthy counterparts chosen to form a control group. Those in both groups were given a gait analysis during dual-task walking at the outset and then assessed using the MoCA scale 12 months later. Statistical analyses were conducted to assess the reliability of gait pa-rameters in predicting cognitive dysfunction, and the area under the receiver operating characteristics curve was calcu-lated. Results On the day after enrollment the variation in step length among the TIA patients with an abnormal step length was compared with variation among the normal controls and among the TIA patients with non-abnormal step-size. The differences were significant. The average walking speed of the TIA patients with an abnormal average walking speed was significantly different from that of the control group and that of the TIA patients with non-abnormal average speed. On the day after enrolling, the accuracy rate of the control group in the dual-task walking test was sig-nificantly better than that of any of the TIA patients, and the accuracy rate of the TIA patients with an abnormal gait in the dual-task walking test was significantly lower than that of the patients with a non-abnormal gait. Twelve months later the number of patients whose MoCA scores were less than 26 in the abnormal gait group was compared with that in the normal gait group, and the difference was statistically significant. The area under the receiver operating charac-teristics curve suggests that both the incidence of step length variation and the average stepping speed could signifi-cantly predict the occurrence of cognitive dysfunction 12 months later. Conclusion Quantitative analysis of gait while dual-task walking can effectively predict the occurrence of cognitive impairment in patients with TIA, and can detect abnormalities earlier than the MoCA scale test.

Objective:To observe the effects of enriched rehabilitation on cognitive function and serum arginine in stroke patients. Methods:From January, 2017 to June, 2018, 40 patients in our department were randomly divided into conventional group (n = 20) and enriched group (n = 20). The conventional group received cognitive rehabilitation, and the enriched group received enriched rehabilitation, once a day, six times a week for three months. Before treatment and three months after treatment, the cognitive function was assessed with Montreal Cognitive Assessment (MoCA), Digit Span Test and Stroop Color Word Test, and the levels of serum arginine and malondialdehyde were detected. Results:Finally, all the patients completed the experiment. There was no significant difference in the scores of MoCA, Digit Span Test and Stroop Color Word Test, and the level of serum arginine and malondialdehyde before treatment (t < 1.243, P > 0.05). Three months after treatment, all the above indexes improved (t > 2.170, P < 0.05), and were better in the enriched group than in the conventional group (t > 2.278, P < 0.05). Conclusion:Enriched rehabilitation could improve the cognitive function of patients after stroke, which might be related to the significant reduction of the elevated serum arginine and reduction of oxidative damage after stroke.

Objective:To compare the total daily doses of 16 active components in big honeyed pills, concentrated pills and tablets of Fuzi Lizhongwan. Method:Three dosage forms of Fuzi Lizhongwan were prepared according to the process described in the literature. RRLC-QqQ-MS was employed to analyze the contents of 16 active ingredients with mobile phase of 0.1%formic acid aqueous solution-0.1%formic acid acetonitrile solution for gradient elution,the separation was performed on a Accucore RP-MS column(2.1 mm×100 mm, 2.6 μm) with a flow rate of 0.3 mL·min^-1 and the column temperature at 30℃, the mass spectrometry condition was electrospray ion source, positive and negative ion switching mode for detection, multi-reaction monitoring mode(MRM) for scanning. The contents of 16 active ingredients were calculated, and the normalization arithmetic method was used for comparing the total daily doses of these active ingredients in three dosage forms of Fuzi Lizhongwan. Result:Processed products of Aconiti Lateralis Radix Praeparata were used as raw powder in preparation process of the three dosage forms, so there was no significant difference in the contents of six alkaloids in the three dosage forms, while the contents of other 10 active ingredients from Zingiberis Rhizoma, Codonopsis Radix, Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle were significantly higher in big honeyed pills than those in concentrated pills or tablets(P<0.01), due to the differences in the extracting solvents(ethanol and water) and ethanol concentration, the contents of other 10 active ingredients between concentrated pills and tablets were also significant differences. The total daily doses of these 16 active components were 18.764, 17.530, 5.676 mg in big honeyed pills, concentrated pills and tablets, respectively. The concentrated pills exhibited the highest normalization arithmetic score of 0.717 5 compared with 0.605 4 and 0.312 4 separately in big honeyed pills and tablets, it was mainly owing to the maximum amount of raw material per day in concentrated pills. Conclusion:The total daily doses of 16 active ingredients in the three dosage forms of Fuzi Lizhongwan are significantly different caused by preparation process, prescription and dosage.