Objective​ To evaluate the clinical characteristics and influencing factors of fatigue in patients with rheumatoid arthritis （RA）， with the aim of providing guidance for clinical treatment. Methods​ Based on the multicenter real-world cohort of the China Registry of Traditional Chinese Medicine for Rheumatism （CERTAIN） platform， patients with RA enrolled from 2019 to 2025 were included. Demographic data， disease assessment indicators， laboratory indices， and traditional Chinese medicine （TCM） syndrome patterns were collected to analyze the TCM syndromes and clinical characteristics of RA patients with fatigue. Spearman correlation analysis and logistic regression analysis were used to identify factors associated with fatigue in RA. Results​ A total of 3 021 patients with RA were included， among whom 2 007 （66.43%） had fatigue. Compared with the non-fatigue group， the fatigue group was older and had a longer disease duration， with significantly higher scores for the 28-joint Disease Activity Score （DAS28）， swollen joint count （SJC）， tender joint count （TJC）， Health Assessment Questionnaire （HAQ）， pain visual analog scale （VAS）， and patient global assessment （PGA） （P<0.01）. Among TCM syndromes， fatigue was more common in patients with dampness-heat obstruction， cold-dampness obstruction， and liver-kidney deficiency syndromes （P<0.05）. Multivariate analysis revealed that morning stiffness duration exhibited a stepwise association with fatigue， while poor appetite， insomnia with frequent dreaming， restlessness， high HAQ scores， and high pain VAS scores were identified as risk factors. ConclusionFatigue is a prominent symptom in patients with RA and is more common among those with dampness-heat obstruction， cold-dampness obstruction， and liver-kidney deficiency syndromes. It is closely associated with disease activity， pain， functional limitation， sleep， and emotional status.

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 observe the early changes of vault after implantation of posterior chamber phakic intraocular lens implantable collamer lens(ICL),and investigate the effect of different implantation axes on the early vault changes.Methods A prospective,parallel cohort study was performed,enrolling a total of 124 eyes of who underwent ICL(V4c)implantation in the refractive clinic.The changes of vault were observed by scheimpflug tomography(Pentacam)and anterior segment optical coherence tomography(CASIA2)at 1 day,1 week and 1 month after surgery.Results The ICL vault declined significantly by approximately(108.2±82.4)μm 1 week after surgery with the proportion of 16.6%±12.1%compared with the values 1 day after surgery(P<0.001),and then remained stable.Within 1 month after surgery,excluding the difference in vault baseline at 1 day after surgery,the proportion of vault decline in the middle vault group(250-749 μm)and the high vault group(≥750 μm)was similar,and there was no statistically significant difference.We analyzed the relationship between ICL axial directions and vault and found that the vault decline of the horizontal ICL group stabilized quickly at 1 week after surgery,and the vault decline of the vertical ICL group was more significant within 1 month after surgery(P<0.05).Conclusion The vault of the ICL shows a downward trend in the early stage after implantation.The middle vault group and ICL in the horizontal position stabilizes faster,and the downward trend of the high vault group or ICL in the vertical position is more obvious.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

This study explored the efficacy and mechanisms of Shenqi Buqi Granules in treating chronic heart failure(CHF) of Qi deficiency using proteomics and bioinformatics methods. A total of 18 healthy participants(health group) and 19 patients with Qi deficiency-type CHF(experimental group) were enrolled and treated with Shenqi Buqi Granules for 12 weeks. Clinical indicators, including Qi deficiency scores, complete blood count, biochemical parameters, lipid profiles, and cardiac function, were collected from pre-and post-experimental groups. Serum proteomics analysis was performed. Differential proteins were screened through differential analysis and K-means clustering. Further analyses, including subcellular localization, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and protein-protein interaction(PPI) network construction, were conducted to identify pathways and proteins associated with Shenqi Buqi Granules treatment. Spearman correlation analysis focused on proteins most correlated with the core phenotype of CHF of Qi deficiency. The results show that Shenqi Buqi Granules treatment reduced Qi deficiency scores and brain natriuretic peptide levels of pre-experimental group. A total of 1 594 proteins were quantified in the proteomics analysis, with 98 proteins showing differential expression between healthy group and experimental group before and after treatment. Subcellular localization analysis revealed 6 protein sources, while KEGG pathway enrichment highlighted biological processes including angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. Core genes identified included CD34, CSF1, CALM1, CALML3, PPP1CA, PFN1, and 3 ribosomal large subunit proteins. Correlation analysis between core proteins and Qi deficiency scores revealed that CD34(r=-0.67, P<0.05) and PPP1CA(r=0.62, P<0.01) were most strongly associated with Qi deficiency scores. This study suggests that Shenqi Buqi Granules improves Qi deficiency scores and CHF symptoms by regulating angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. CD34 and PPP1CA are identified as core proteins involved in the therapeutic effects of Shenqi Buqi Granules on Qi deficiency.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Heart Failure/metabolism* ; Male ; Female ; Proteomics ; Middle Aged ; Qi ; Aged ; Protein Interaction Maps/drug effects* ; Adult ; Chronic Disease

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 observe the early changes of vault after implantation of posterior chamber phakic intraocular lens implantable collamer lens(ICL),and investigate the effect of different implantation axes on the early vault changes.Methods A prospective,parallel cohort study was performed,enrolling a total of 124 eyes of who underwent ICL(V4c)implantation in the refractive clinic.The changes of vault were observed by scheimpflug tomography(Pentacam)and anterior segment optical coherence tomography(CASIA2)at 1 day,1 week and 1 month after surgery.Results The ICL vault declined significantly by approximately(108.2±82.4)μm 1 week after surgery with the proportion of 16.6%±12.1%compared with the values 1 day after surgery(P<0.001),and then remained stable.Within 1 month after surgery,excluding the difference in vault baseline at 1 day after surgery,the proportion of vault decline in the middle vault group(250-749 μm)and the high vault group(≥750 μm)was similar,and there was no statistically significant difference.We analyzed the relationship between ICL axial directions and vault and found that the vault decline of the horizontal ICL group stabilized quickly at 1 week after surgery,and the vault decline of the vertical ICL group was more significant within 1 month after surgery(P<0.05).Conclusion The vault of the ICL shows a downward trend in the early stage after implantation.The middle vault group and ICL in the horizontal position stabilizes faster,and the downward trend of the high vault group or ICL in the vertical position is more obvious.

Objective To observe the clinical efficacy of acupuncture at Neiyingxiang(EX-HN09)points combined with western medicine in the treatment of allergic rhinitis of deficiency-cold of lung qi type.Methods Sixty patients with deficiency-cold of lung qi type of allergic rhinitis were randomly divided into observation group and control group,with 30 patients in each group.The control group was treated with Desloratadine Tablets combined with Mometasone Furoate Aqueous Nasal Spray,and the observation group was treated with acupuncture at Neiyingxiang points combined with the self-made rhinitis recipe on the basis of the control group,and the clinical efficacy of the two groups was evaluated after 14 days.The changes of nasal symptom scores,Visual Analogue Scale(VAS)and rhinoconjunctivitis quality of life scores of the patients of the two groups were observed before and after the treatment.After 14 days of treatment,the clinical efficacy of the two groups was evaluated.The changes in nasal symptom scores,as well as VAS and rhinoconjunctivitis quality of life questionnaire(RQLQ)scores were observed before and after treatment.The changes in traditional Chinese medicine(TCM)sydnrome scores and serum immunoglobulin E(IgE)were compared before and after treatment in the two groups,and the safety of the two groups was evaluated.Results(1)The total effective rate of the observation group was 93.33%(28/30),and the control group was 73.33%(22/30).The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the symptoms of nasal congestion,sneezing,runny nose and nasal itching were significantly improved in the two groups(P＜0.01),and the observation group was significantly superior to the control group in improving nasal symptoms,and the differences were statistically significant(P＜0.05).(3)After treatment,the VAS scores of patients in the two groups were significantly improved(P＜0.01),and the observation group was superior to the control group in improving VAS scores,with statistically significant differences(P＜0.05).(4)After treatment,the PQLQ scores of patients in the two groups improved significantly(P＜0.01),and the observation group was significantly superior to the control group in improving the PQLQ scores,and the difference was statistically significant(P＜0.05).(5)After treatment,the TCM syndrome scores of the patients in the two groups were significantly improved(P＜0.01),and the observation group was significantly superior to the control group in improving TCM syndrome scores,with statistically significant differences(P＜0.05).(6)After treatment,the serum IgE levels of patients in the two groups were significantly improved(P＜0.01),and the observation group was significantly superior to the control group in improving serum IgE levels(P＜0.05),with a statistically significant difference.(7)There was no significant difference in the incidence of adverse reactions between the observation group and the control group(P＞0.05).Conclusion Acupuncture at Neiyingxiang points plus self-made rhinitis recipe combined with western medicine in the treatment of deficiency-cold of lung qi type of allergic rhinitis can significantly improve the clinical symptoms of the patients,thus improving the quality of life of the patients,and the therapeutic efficacy is remarkable.

Objective To explore the clinical efficacy of Chinese herbal medicine with the actions of invigorating spleen,activating blood and resolving phlegm in the treatment of senile insomnia based on the theory of"muscular atrophy,qi-passage blockage"recorded in Huang Di Nei Jing(The Yellow Emperor's Inner Classic,shortened as Nei Jing).Methods A total of 120 elderly patients with insomnia were randomly divided into observation group and control group,with 60 cases in each group.The control group was treated with oral use of Dexzopiclone Tablets,and the observation group was treated with oral use of decoction of Chinese herbal medicine for invigorating spleen,activating blood and resolving phlegm.The course of treatment covered 4 weeks.Before and after treatment,the two groups were observed in the changes of Pittsburgh Sleep Quality Index(PSQI)score,Insomnia Severity Index(ISI)score,polysomnography(PSG)related parameters of total sleep time(TST),number of awakenings(AN)and sleep latency(SL),mean blood flow velocity of anterior cerebral artery(ACA),middle cerebral artery(MCA),and posterior cerebral artery(PCA),and serum levels of 5-hydroxytryptamine(5-HT)and melatonin(MT).After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 93.33%(56/60),which was slightly higher than 90.00%(54/60)of the control group,but the difference was not statistically significant(P＞0.05).(2)After treatment,the item scores and total scores of PSQI in the two groups were lower than those before treatment(P＜0.05),and the decrease of the scores of sleep quality,sleep time,sleep efficiency,and daytime function as well as total scores in the observation group was significantly superior to that in the control group(P＜0.05).However,there was no significant difference of time for falling asleep and sleep disorder scores between the two groups(P＞0.05).After 4 weeks of drug withdrawal,the item scores of PSQI in the observation group continued to decrease compared with those after treatment(P＜0.05),but there was no significant difference in the control group(P＜0.05).(3)After treatment,the ISI scores in the two groups were decreased when compared with those before treatment(P＜0.05),and the decrease in the observation group was superior to that in the control group(P＜0.05).After 4 weeks of drug withdrawal,the ISI score of the observation group continued to decrease compared with that after treatment(P＜0.05),while the control group had no significant change,and the difference was not statistically significant(P＞0.05).(4)After treatment,the PSG related parameters such as TST,AN and SL in the two groups were improved when compared with those before treatment(P＞0.05),and the improvement of TST and AN in the observation group was superior to that in the control group(P＞0.05).(5)After treatment,the mean blood flow velocity of ACA,MCA and PCA in the observation group was improved compared with that before treatment(P＜0.05),while there was no significant change in the control group compared with that before treatment(P＞0.05).The improvement of the mean blood flow velocity of ACA,MCA and PCA in the observation group was significantly superior to that in the control group(P＜0.05).(6)After treatment,the levels of serum 5-HT and MT in the two groups were increased when compared with those before treatment(P＜0.05),and the increase in the observation group was superior to that in the control group(P＜0.05).(7)The incidence of adverse reactions in the observation group was 5.00%(3/60),which was slightly lower than 13.33%(8/60)in the control group,but the difference was not statistically significant(P＞0.05).Conclusion Based on the theory of"muscular atrophy,qi-passage blockage"recorded in Nei Jing,the Chinese herbal medicine for invigorating spleen,activating blood and resolving phlegm exerts certain effect in treating senile insomnia.It can effectively improve the sleep quality and daytime function of patients,enhance sleep efficiency,increase sleep time,reduce the number of awakenings,alleviate the severity of insomnia,improve brain function,and regulate the level of neurotransmitters,with remarkably long-term effect and reliable safety.

Objective To observe the clinical efficacy of ZHU's scalp acupuncture combined with Danzhi Xiaoyao San in the treatment of tinnitus of liver constraint transforming into fire type.Methods A total of 70 patients with tinnitus of liver constraint transforming into fire type were randomly divided into treatment group and control group,35 cases in each group.The treatment group was treated with ZHU's scalp acupuncture combined with Danzhi Xiaoyao San,and the control group was treated with Yinxingye Tablets and Mecobalamin Tablets.The course of treatment was three weeks.After three weeks of treatment,the clinical efficacy of the two groups was evaluated,and telephone follow-up was conducted at three and six months after the end of treatment to evaluate the clinical efficacy.The changes of Tinnitus Evaluation Scale(TEQ)Score and Self-Rating Anxiety Scale(SAS)score were observed before and after treatment in the two groups.The changes of Tinnitus Handicap Inventory(THI)scores were compared before and after treatment between the two groups.The safety and adverse reactions of the two groups were evaluated.Results(1)After treatment,the total effective rate of the treatment group was 88.57%(31/35),and that of the control group was 62.86%(22/35),and the therapeutic efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the TEQ,SAS,and THI scores of the two groups were significantly improved(P＜0.01),and the treatment group was significantly superior to the control group in improving TEQ,SAS,and THI scores,and the differences were statistically significant(P＜0.05).(3)At the 3-month follow-up after the end of treatment,the overall effective rate was 85.71%(30/35)in the treatment group and 60.00%(21/35)in the control group.At the 6-month follow-up after the end of treatment,the overall effective rate was 82.86%(29/35)in the treatment group and 54.29%(19/35)in the control group.At the 3-and 6-month follow-up after the end of treatment,the efficacy of the treatment group was superior to that of the control group,and the differences were statistically significant(P＜0.05).(4)No obvious adverse reactions were seen in the two groups of patients,and the difference in the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion ZHU's scalp needling combined with Danzhi Xiaoyao San for the treatment of tinnitus of liver constraint transforming into fire type can significantly improve the tinnitus symptoms of patients,with high safety,no adverse reactions,and remarkable efficacy.