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

INTRODUCTION: Adverse childhood experiences (ACEs) are associated with significant long-term impacts, yet few interventions specifically target ACE exposure, especially in Asian populations. Anchor, Singapore's first home visitation programme, addresses maltreat-ment among preschool children. This study evaluated Anchor's impact on children's developmental and behavioural outcomes. METHOD: We conducted a prospective evaluation of children under 4 years assessed for maltreatment from November 2019 to July 2023. Developmental and behavioural progress was measured every 6 months using the Ages and Stages Questionnaires (ASQ-3) and ASQ:Social-Emotional (ASQ:SE-2), and annually using the Child Behaviour Checklist (CBCL). RESULTS: The results of 125 children (mean age 20.0 months, 48% female) were analysed. The mean length of stay in programme was 21.2 (7.3) months. At baseline, 92 (73.6%) children were at risk of develop-mental delay and 25 (31.7%) children aged ≥18 months had behavioural concerns. The programme was associated with significant improvements in gross motor (P=0.002) and fine motor (P=0.001) domains of the ASQ-3 and internalising problem scale (P=0.001) of the CBCL. CONCLUSION Anchor effectively enhances develop-mental and behavioural outcomes for children exposed to maltreatment. Targeted early intervention through such programmes can mitigate adverse impacts, optimising developmental trajectories and potentially reducing the long-term clinical and economic burdens associated with ACEs.
Humans ; Female ; Male ; Child Abuse/therapy* ; Child, Preschool ; Singapore ; House Calls ; Infant ; Prospective Studies ; Child Development ; Developmental Disabilities/epidemiology* ; Program Evaluation ; Child Behavior Disorders ; Child Behavior

Objective To analyze the classification characteristics of rheumatoid arthritis(RA)-related antibodies and to investigate the factors influencing the development of RA-related interstitial pulmonary diseases(RA-ILD)in RA patients using latent class analysis(LCA).Methods A retrospective analysis of 712 RA patients treated at the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University from December 2019 to October 2022 was conducted.According to whether patients had RA-ILD or not,they were divided into simple RA group(n=523)and RA-ILD group(n=189).Then,the differences in general data,clinical features,medication use and laboratory indicators were compared between the two groups.Based on the differences in RA-related antibody indicators,712 patients were divided into 3 latent categories using LCA:high-risk group(n=364),medium-risk group(n=205),and low-risk group(n=143).One-way analysis of variance was employed to compare clinical characteristics of the 3 groups,and the prevalence of RA-ILD was calculated.Multivariate logistic regression analysis was utilized to identify independent affect factors of RA-ILD.Results Significant differences in gender,age,and smoking history were observed between simple RA group and RA-ILD group(P<0.05).The high,medium and low risk groups exhibited significant differences in gender,age,prednisone(PRED)and methotrexate(MTX)medication history,Red blood cell count(RBC),interleukin-2(IL-2),IL-4,IL-10,IL-17,TNF-α,interferon-γ(INF-γ),serum globulins,and white blood albumins(P<0.05).The high-risk group had a higher proportion of males,RBC,IL-2,IL-4,IL-10,IL-17,TNF-α,INF-γ,and serum globulin levels,and a lower proportion of MTX medication compared with medium-and low-risk groups(P<0.05 or P<0.01).The medium-risk group had a higher proportion of MTX administration than that in high-and low-risk groups(P<0.05 or P<0.01).The low-risk group had a higher proportion of females and older age than those in other two groups(P<0.05 or P<0.01).The prevalence of RA-ILD was 30.5%,23.9%and 20.3%in the three groups,respectively.Multivariate logistic regression analysis indicated that male(OR=2.920,95%CI 1.722-4.952),age(OR=1.055,95%CI 1.035-1.074),IL-17(OR=1.013,95%CI 1.003-1.023),TNF-α(OR=1.050,95%CI 1.017-1.083),INF-γ(OR=0.962,95%CI 0.932-0.993),Serum albumin(OR=0.919,95%CI 0.869-0.971)and high risk antibody indicators(OR=1.725,95%CI 1.084-2.745)were independent predictors for RA-ILD.Conclusions RA patients exhibit distinct categories of antibody indicators,with a higher prevalence in high-risk patients with RA-ILD.RA-ILD is more likely to occur in male,elderly patients with abnormal liver function and high-risk antibody indictors.More attention should be paid to these patients and individualized interventions should be developed and implemented in a timely manner to improve the quality of patient survival.

Objective To give references for future study,the current state of research and identify key areas of interest,and development trends in the field of Chinese Materia Medica interventions for PD were examined.Methods Literature on Chinese Materia Medica treatment of PD published between 2004 and 2024 was retrieved from the China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)databases.After screening,689 articles were included(412 in Chinese,277 in English).CiteSpace software was used for bibliometric and knowledge graph analysis,generating author collaboration networks,institutional collaboration networks,keyword clustering,timeline maps,and keyword burst analysis.Results Over the past two decades,the number of publications has continued to grow globally.Chinese-language studies focused primarily on clinical research,with core authors such as Yi Liu,Jiancheng He,and Jianfen Liang,and institutions like Guangxi University of Chinese Medicine making significant contributions.English-language literature emphasized mechanistic studies,with Kyung Hee University and Beijing University of Chinese Medicine as leading research teams.High-frequency keywords included"Parkinson's disease"(346 occurrences),"traditional Chinese medicine(TCM)"(60 occurrences),and"oxidative stress"(11 occurrences).Keyword clustering revealed research hotspots in TCM formulas(e.g.,Zhichan decoction),mechanisms(e.g.,oxidative stress),and integrated TCM-Western medicine therapies(e.g.,Madopar).Burst analysis indicated emerging frontiers in the gut-brain axis,iron metabolism,molecular docking,gut microbiota,and signaling pathways.Conclusions Although there is a lot of potential for treating PD in TCM,there are also a lot of challenges.In order to realize the transformation of TCM from a supportive to a mainstream treatment for PD,and to bring better efficacy to patients in the future,it is necessary to strengthen evidence-based research,deepen the research of mechanisms,promote the construction of standards,explore the integration of Chinese and Western medicine,and improve the evaluation system.

Objective To investigate the underlying mechanism of Hongyu Decoction in the treatment of inflammatory bowel disease(IBD)based on serum amino acid metabolism.Methods A total of 50 male C57BL/6J mice were divided into control group,model group,sulfasalazine(SASP)group and Hongyu Decoction low-and high-dosage groups,with 10 mice in each group.Except for the control group,the rest groups were treated with 3%dextran sulfate sodium freely for seven consecutive days to establish the IBD model.The SASP group was given SASP solution at a dosage of 200 mg/kg by gavage,while the Hongyu Decoction low-and high-dosage groups were given Hongyu Decoction freeze-dried powder solution at dosages of 0.5 and 2.0 g/kg respectively by gavage for 11 consecutive days.The general condition was monitored and DAI score were calculated.After the mice were sacrificed,the length of colons was measured,ELISA was used to detect serum TNF-α,IL-1β,IL-17 contents,HE staining was used to observe the morphology of colon tissue,and Alizarin blue staining was used to evaluate the secretion of mucin levels by intestinal epithelial goblet cells,UPLC-MS and multivariate statistical methods were used to analyze the serum amino acid metabolism profiles of mice in the control group,model group and Hongyu Decoction high-dosage group,and differential amino acids were screened.Pathway enrichment analysis was performed on differential amino acids using MetaboAnalyst 5.0.Results Compared with the control group,the DAI score of the model group mice significantly increased(P<0.001),the colon length was significantly shortened(P<0.001),and the serum contents of TNF-α,IL-1β and IL-17 significantly increased(P<0.001);with widespread ulceration of colon tissue,disappearance of mucosal epithelium and intestinal crypt structure,infiltration of lymphocytes and neutrophils,congestion and edema of intestinal mucosa,proliferation of submucosal connective tissue,reduced number of colonic goblet cells and mucin secretion.Compared with the model group,the Hongyu Decoction high-dosage group showed a significant decrease in DAI score(P<0.001),while the SASP group and the Hongyu Decoction low-and high-dosage groups showed a significant increase in colon length(P<0.05,P<0.001),and the serum contents of TNF-α,IL-1β and IL-17 were significantly reduced(P<0.001);the colonic villi were relatively intact,the glands were clear and arranged neatly,the branches of the intestinal crypts were obvious,no obvious edema was observed,and the number of colonic goblet cells and mucin secretion increased.Seven potential biomarkers for IBD in mice were identified through serum metabolomics screening,including tryptophan,serine,glutamate,valine,histidine,methionine and phenylalanine;two potential biomarkers for the treatment of IBD with Hongyu Decoction were identified,namely valine and tyrosine.The results of pathway enrichment analysis showed that the differential amino acids in the model group mainly involved the biosynthesis of phenylalanine,tyrosine and tryptophan,histidine metabolism,cysteine and methionine metabolism,phenylalanine metabolism and arginine biosynthesis;the differential amino acids in Hongyu Decoction high-dosage group mainly involved the biosynthesis of phenylalanine,tyrosine and tryptophan,as well as the metabolism of alanine,aspartate and glutamate,and the biosynthesis of arginine.Conclusion Hongyu Decoction can improve intestinal epithelial damage and inflammatory cell infiltration in IBD mice,protect the integrity of the intestinal mucosal barrier,and may be related to regulating amino acid metabolism in the body.

Objective To give references for future study,the current state of research and identify key areas of interest,and development trends in the field of Chinese Materia Medica interventions for PD were examined.Methods Literature on Chinese Materia Medica treatment of PD published between 2004 and 2024 was retrieved from the China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)databases.After screening,689 articles were included(412 in Chinese,277 in English).CiteSpace software was used for bibliometric and knowledge graph analysis,generating author collaboration networks,institutional collaboration networks,keyword clustering,timeline maps,and keyword burst analysis.Results Over the past two decades,the number of publications has continued to grow globally.Chinese-language studies focused primarily on clinical research,with core authors such as Yi Liu,Jiancheng He,and Jianfen Liang,and institutions like Guangxi University of Chinese Medicine making significant contributions.English-language literature emphasized mechanistic studies,with Kyung Hee University and Beijing University of Chinese Medicine as leading research teams.High-frequency keywords included"Parkinson's disease"(346 occurrences),"traditional Chinese medicine(TCM)"(60 occurrences),and"oxidative stress"(11 occurrences).Keyword clustering revealed research hotspots in TCM formulas(e.g.,Zhichan decoction),mechanisms(e.g.,oxidative stress),and integrated TCM-Western medicine therapies(e.g.,Madopar).Burst analysis indicated emerging frontiers in the gut-brain axis,iron metabolism,molecular docking,gut microbiota,and signaling pathways.Conclusions Although there is a lot of potential for treating PD in TCM,there are also a lot of challenges.In order to realize the transformation of TCM from a supportive to a mainstream treatment for PD,and to bring better efficacy to patients in the future,it is necessary to strengthen evidence-based research,deepen the research of mechanisms,promote the construction of standards,explore the integration of Chinese and Western medicine,and improve the evaluation system.

Objective To investigate the underlying mechanism of Hongyu Decoction in the treatment of inflammatory bowel disease(IBD)based on serum amino acid metabolism.Methods A total of 50 male C57BL/6J mice were divided into control group,model group,sulfasalazine(SASP)group and Hongyu Decoction low-and high-dosage groups,with 10 mice in each group.Except for the control group,the rest groups were treated with 3%dextran sulfate sodium freely for seven consecutive days to establish the IBD model.The SASP group was given SASP solution at a dosage of 200 mg/kg by gavage,while the Hongyu Decoction low-and high-dosage groups were given Hongyu Decoction freeze-dried powder solution at dosages of 0.5 and 2.0 g/kg respectively by gavage for 11 consecutive days.The general condition was monitored and DAI score were calculated.After the mice were sacrificed,the length of colons was measured,ELISA was used to detect serum TNF-α,IL-1β,IL-17 contents,HE staining was used to observe the morphology of colon tissue,and Alizarin blue staining was used to evaluate the secretion of mucin levels by intestinal epithelial goblet cells,UPLC-MS and multivariate statistical methods were used to analyze the serum amino acid metabolism profiles of mice in the control group,model group and Hongyu Decoction high-dosage group,and differential amino acids were screened.Pathway enrichment analysis was performed on differential amino acids using MetaboAnalyst 5.0.Results Compared with the control group,the DAI score of the model group mice significantly increased(P<0.001),the colon length was significantly shortened(P<0.001),and the serum contents of TNF-α,IL-1β and IL-17 significantly increased(P<0.001);with widespread ulceration of colon tissue,disappearance of mucosal epithelium and intestinal crypt structure,infiltration of lymphocytes and neutrophils,congestion and edema of intestinal mucosa,proliferation of submucosal connective tissue,reduced number of colonic goblet cells and mucin secretion.Compared with the model group,the Hongyu Decoction high-dosage group showed a significant decrease in DAI score(P<0.001),while the SASP group and the Hongyu Decoction low-and high-dosage groups showed a significant increase in colon length(P<0.05,P<0.001),and the serum contents of TNF-α,IL-1β and IL-17 were significantly reduced(P<0.001);the colonic villi were relatively intact,the glands were clear and arranged neatly,the branches of the intestinal crypts were obvious,no obvious edema was observed,and the number of colonic goblet cells and mucin secretion increased.Seven potential biomarkers for IBD in mice were identified through serum metabolomics screening,including tryptophan,serine,glutamate,valine,histidine,methionine and phenylalanine;two potential biomarkers for the treatment of IBD with Hongyu Decoction were identified,namely valine and tyrosine.The results of pathway enrichment analysis showed that the differential amino acids in the model group mainly involved the biosynthesis of phenylalanine,tyrosine and tryptophan,histidine metabolism,cysteine and methionine metabolism,phenylalanine metabolism and arginine biosynthesis;the differential amino acids in Hongyu Decoction high-dosage group mainly involved the biosynthesis of phenylalanine,tyrosine and tryptophan,as well as the metabolism of alanine,aspartate and glutamate,and the biosynthesis of arginine.Conclusion Hongyu Decoction can improve intestinal epithelial damage and inflammatory cell infiltration in IBD mice,protect the integrity of the intestinal mucosal barrier,and may be related to regulating amino acid metabolism in the body.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

ObjectiveTo evaluate the effect of antihypertensive and lipid-regulating Chinese patent medicine combined with conventional Western medicine in the treatment of hypertension with dyslipidemia. To carry out the evidence synthesis of clinical research and provide evidence-based evidence support for clinical decision-making. MethodThe databases including China National Knowledge Infrastructure （CNKI），Wanfang Data Knowledge Service Platform （WF），VIP，SinoMed，Embase，PubMed，Web of Science （WOS），and the Cochrane Library were searched for randomized controlled trials （RCT） of all listed Chinese patent medicines in the treatment of hypertension with dyslipidemia from the establishment of the databases to April 15，2023. The literature was screened and extracted，and the risk of bias tool 2.0 （RoB2） was used to assess the quality and risk of bias of the methodology. Revman 5.4.1 software was used to analyze the outcome indicators. Grading of Recommendations Assessment，Development and Evaluation （GRADE） was applied to assess the quality of evidence formed by clinical research data. The inclusion and recommendation of Chinese patent medicines in the National Drug Catalogue for Basic Medical Insurance，Work-related Injury Insurance and Maternity Insurance （2022） and domestic guidelines and consensus were searched to form a bubble chart. ResultA total of 15 studies were included. The evaluation of the methodological quality of each study showed that the risk of bias stemmed from the lack of blinding and allocation concealment，and low sample size. The comprehensive analysis of clinical studies showed that Dengzhan Shengmai capsules combined with rosuvastatin and amlodipine besylate，Yindan Xinnaotong capsules combined with simvastatin and levamlodipine tablets，Xiaoshuan Tongluo capsules combined with nifedipine controlled release tablets and pravastatin sodium tablets，Xinshubao capsules combined with atorvastatin calcium tablets and irbesartan，Wenyading capsules combined with enalapril，and Jiangzhining tablets combined with conventional Western medicines were all superior to conventional Western medicines used in the control group in improving systolic blood pressure （SBP），diastolic blood pressure （DBP），cholesterol （TC），triglyceride （TG），low density lipoprotein cholesterol （LDL-C），and high density lipoprotein cholesterol （HDL-C）. There was no significant difference in the incidence of adverse reactions between the two groups. The GRADE evaluation of the main outcome indicators showed that the evidence quality of SBP and incidence of adverse reactions was graded as B，that of DBP as C，and that of total TC，TG，LDL-C，and HDL-C as D. The evaluation of Chinese patent medicines covered by medical insurance and recommended by guidelines and consensus showed that Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules belonged to class B drugs of medical insurance，and were recommended for 7，6 and 3 times in the guidelines and consensus，respectively. ConclusionCompared with simple medicine treatment，Chinese patent medicine combined with conventional Western medicine has more advantages in improving blood pressure and blood lipid，and shows higher safety. Among them，Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules have stronger clinical applicability and economy. All the trials included in this article adhered to the principle of randomization and reported the outcome measures. However，the quality of evidence in related clinical studies was low. In terms of trial design，large-sample，multi-center，blinded randomized controlled trials based on the consolidated standards of reporting trials （CONSORT） statement are still needed for comprehensive trial designs and reporting，to further improve the GRADE quality evaluation and guideline formulation under the guidance of evidence-based medicine，so as to provide higher quality evidence-based research evidence for clinical decision-making.

ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension， synthesize and update the evidence， form expert consensus， and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure （CNKI）， WanFang Data Knowledge Service Platform （WanFang）， Vip Chinese Science and Technology Journal Database （VIP）， Chinese Biomedical Literature Service System （Sinomed）， National Library of Medicine （PubMed）， Cochrane Library， Web of Science， and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31， 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment， Development， and Evaluation profiler （GRADEprofiler） 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included， and the results of literature quality evaluation and risk of bias showed that 70.31% （45/64） of the studies indicated some risks， and 29.69% （19/64） indicated high risks. Compared with conventional western medicines， the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure （SBP） and diastolic pressure （DBP）， increase the effective rate of antihypertensive， reduce the incidence of adverse reactions， endothelin-1， and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive， and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive， without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive， and Xinmaitong capsules decreased DBP， with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally， four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension， antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety， but they are mostly weak recommendations in terms of efficacy， and more high-quality evidence is needed.