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

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Constipation is a prevalent ailment which might significantly impact the quality of people's life and rise some associated deseases risks. In this study, a chronic constipation mouse model was established using loperamide hydrochloride. Mice were gavaged an Angelica sinensis Cistanche Fiber Compound, comprised of Dang Gui [Angelica sinensis (Oliv.) Diels], Rou Cong Rong (Cistanche deserticola Y.C.Ma), wheat fiber, and low-molecular-weight xylan at high dosage (3.6 g·kg^-1, 30 times the recommended human dose) and low dosage (0.6 g·kg^-1, 5 times the recommended human dose) for 14 days. The study assessed the therapeutic efficacy of the compound by observing fecal morphology, measuring water content, and conducting small intestine motility experiments. Furthermore, enzyme-linked immunosorbent assays (ELISA) were conducted to evaluate the serum levels of gastrointestinal hormones including motilin (MTL), gastrin (GAS), the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Histopathological examination with H&E staining was employed to evaluate colonic tissue damage. Additionally, Western blot and immunohistochemistry experiments were conducted to examine the expression levels of aquaporin-3 (AQP3) and c-Kit in the colon. The results indicated that the Angelica sinensis Cistanche Fiber Compound could improve fecal morphology, increase fecal water content, enhance small intestinal transit rates in mice. Additionally, there was a significant elevation in the serum levels of gastrointestinal hormones and a notable reduction in the levels of inflammatory factors. The improvement in colonic histopathological damage was accompanied by a marked decrease in the expression of the colonic water channel protein AQP3 and a significant increase in c-Kit expression. These results collectively suggested the presence of a dose-response relationship. These findings indicate that the Angelica sinensis Cistanche Fiber Compound effectively alleviates constipation in mice. Its action is associated with the regulation of colonic water channel protein AQP3 and c-Kit expression, along with the modulation of serum inflammatory factors and gastrointestinal hormones. This experiment was approved by the Animal Experiment Ethics Committee of Jinan University.

This study aimed to investigate the potential role of Colquhounia Root Tablets against bone destruction in rheumatoid arthritis(RA) and its molecular mechanism. The study used ultra-performance liquid chromatography-mass spectrometry to analyze the major components of Colquhounia Root Tablets and predicted its candidate target gene set based on the major components. The key targets of RA bone destruction were obtained through GeneCards and the Database of Genetics and Medical Literature(OMIM), protein-protein interaction(PPI) network was constructed, and the key targets were identified by topological analysis. The molecular mechanism of Colquhounia Root Tablets against RA bone destruction was further revealed using Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. The effects of Colquhounia Root Tablets on macrophage viability was assessed by MTS assay and screened for non-toxic concentrations. A model of receptor activator of nuclear factor-κB(RANKL) induced osteoclast differentiation in vitro was constructed. Colquhounia Root Tablets were used to observe the formation and differentiation of osteoclasts by tartrate-resistant acid phosphatase(TRAP) staining and fibrous actin(F-actin) staining, and the effects of Colquhounia Root Tablets on the changes of core target proteins in the osteoclast differentiation system were detected by immunofluorescence and Western blot. The results showed that the main components of Colquhounia Root Tablets included 14 compounds such as triptolide, celastrol, and triptophenolide. Further network analysis revealed that heat-shock protein 90(HSP90) was the key target gene of Colquhounia Root Tablets for anti-RA bone destruction. TRAP staining and F-actin staining showed that the number and area of TRAP-positive polymorphonuclear cells, as well as actin rings, were reduced in a dose-dependent manner after the intervention of Colquhounia Root Tablets(P<0.01). Western blot results showed that the expression of HSP90 protein was significantly reduced after intervention with Colquhounia Root Tablets at 20 and 40 μg·mL~(-1)(P<0.01); Colquhounia Root Tablets at 10 μg·mL~(-1) could significantly decrease the expression of necrosis factor receptor associated molecule 6(TRAF6) and nuclear factor of activated T cells 1(NFATc1) proteins(P<0.01); moreover, all doses of Colquhounia Root Tablets significantly reduced the expression of osteoclast differentiation marker proteins matrix metalloproteinase 9(MMP9) and cathepsin K(CTSK)(P<0.01).Immunofluorescence results further confirmed that Colquhounia Root Tablets significantly inhibited HSP90 and CTSK levels, as well as NFATc1 activation in osteoblasts. In conclusion, the present study confirmed that Colquhounia Root Tablets may inhibit RANKL-induced osteoclast differentiation by regulating the key target of HSP90, thus exerting an anti-RA bone destruction effect, which will provide a new idea for Colquhounia Root Tablets to prevent and treat bone destruction in rheumatoid arthritis.
Osteoclasts/metabolism* ; Mice ; Animals ; Cell Differentiation/drug effects* ; HSP90 Heat-Shock Proteins/genetics* ; Drugs, Chinese Herbal/chemistry* ; Plant Roots/chemistry* ; Humans ; Arthritis, Rheumatoid/physiopathology* ; Protein Interaction Maps/drug effects*

OBJECTIVE: Functional constipation (FC) is a common intestinal disease worldwide. Despite the presence of criteria such as Roman IV, there is no standardized diagnosis and treatment algorithm in Hong Kong that combines both Western and Chinese medicine approaches. This study integrates current effective and safe diagnosis and treatment methods for FC and provides a clear and scientific pathway for clinical professionals and patients. METHODS: A systematic search of the PubMed, Cochrane Library, and China National Knowledge Infrastructure databases was performed from their inception to June 30th, 2022, collecting the current evidence about the efficacious integrative management for FC. We organized a meeting of professionals in fields relevant to treatment and management of FC to develop a consensus agreement on clinical pathway process. RESULTS: We developed a clinical pathway for the treatment of FC based on the most recent published guidelines and consultation with experts. This pathway includes a hierarchy of recommendations for every step of the clinical process, including clinical intake, diagnostic examination, recommended labs, diagnostic flowchart, and guidance for selection of therapeutic drugs. CONCLUSION This pathway establishes clinical standards for the diagnosis and treatment of FC using Chinese medicine and Western medicine; it will help to provide high-quality medical services in Hong Kong for patients with FC. Please cite this article as: Wei DJ, Li HJ, Lyu ZP, Lyu AP, Bian ZX, Zhong LL. A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong, China. J Integr Med. 2023; 21(6): 550-560.
Humans ; Hong Kong ; Integrative Medicine ; Critical Pathways ; China ; Constipation/therapy*

ObjectiveTo observe the effects of modified Chaihu Shugansan（CHSG） and its disassembled formulas on angiotensin-converting enzyme 2 （ACE2）-angiotensin （Ⅰ-Ⅶ） ［Ang （Ⅰ-Ⅶ）］-mitochondrial assembly receptor （MasR） axis in hyperlipidemic rats with myocardial ischemia and depression， and to explore the underlying mechanism of its prevention and treatment of myocardial ischemia and depression. MethodA total of 108 male SD rats were randomly divided into a normal group， a model group， a modified CHSG group （11.7 g·kg^-1）， a Quyu Huatan disassembled formula group （4.05 g·kg^-1）， a Shugan Xingqi disassembled formula group （3.15 g·kg^-1）， a Jianpi Yangxue disassembled formula group （4.5 g·kg^-1）， a fluoxetine group （0.001 8 g·kg^-1）， a trimetazidine group （0.005 4 g·kg^-1）， and a simvastatin group （0.001 8 g·kg^-1）， with 12 rats in each group. The hyperlipidemia model with myocardial ischemia and depression was induced with a high-fat diet combined with injection of isoproterenol （ISO） and chronic unpredictable mild stress （CUMS） in rats in the model group and groups with drug intervention for eight weeks. The rats in each group with drug intervention were treated correspondingly by gavage from the first day of modeling， while those in the normal group and the model group received the same amount of normal saline. The behavioral changes of rats in each group were observed by open field test and forced swimming test. Left ventricular fractional shortening （LVFS） and left ventricular ejection fraction （LVEF） were measured by echocardiography. The serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected by the enzyme-labeled apparatus. Hematoxylin-eosin （HE） staining was used to observe the histomorphological changes of the heart. The serum levels of angiotensin Ⅱ （AngⅡ）， ACE2， and Ang（Ⅰ-Ⅶ） were detected by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression of ACE2 and MasR in the hippocampus and the heart was detected by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the normal group， the model group showed reduced movement time， distance， and average speed in the central area of the open field （P<0.01）， prolonged immobility time of rats in the forced swimming test （P<0.01）， decreased LVFS and LVEF （P<0.01）， inflammatory exudation and disorderly arranged fiber in heart tissues， elevated serum levels of TC， LDL-C， AngⅡ， ACE2 and Ang（Ⅰ-Ⅶ）， diminished HDL-C （P<0.01）， dwindled mRNA and protein expression of ACE2 in the hippocampus and the heart and MasR in the hippocampus， and up-regulated mRNA and protein expression of MasR in the heart （P<0.01）. Compared with the model group， the modified CHSG group displayed increased movement time， distance， and average speed in the center area of the open field （P<0.01）， shortened immobility time in the forced swimming test （P<0.01）， increased LVFS and LVEF （P<0.01）， relieved heart injury， reduced serum levels of TC， LDL-C， AngⅡ， ACE2， and Ang（Ⅰ-Ⅶ）， elevated level of HDL-C （P<0.01）， up-regulated mRNA and protein expression of ACE2 in the hippocampus and the heart and MasR in the hippocampus， and down-regulated mRNA and protein expression of MasR in the heart （P<0.01）. Each disassembled formula could improve the above indexes to a certain extent （P<0.05， P<0.01）， but the effect of the whole formula was optimal. ConclusionThe modified CHSG and its disassembled formulas have the effects of resisting depression， improving myocardial injury， and reducing blood lipid. Due to the synergistic effects of stasis-resolving/phlegm-eliminating drugs， liver-smoothing/Qi-moving drugs， and spleen-tonifying/blood-nourishing drugs in the formula， the modified CHSG is superior to each disassembled formula in efficacy. Its mechanism may be related to the activation of the ACE2-Ang （Ⅰ-Ⅶ）-MasR axis.

Three tricyclic [6,5,7] and six tetracyclic [6,5,5,5] novel indole alkaloids were synthesized and evaluated on triglyceride inhibitory activities for the first time. Among them, compound 4c showed the most potent activity with IC₅₀ value of 6.35 μmol·L^-1. Meanwhile, compound 4c also exhibited a good safety profile at the cellular level. Preliminary mechanism study indicated that 4c might increase intracellular lipid metabolism by activating AMPK. These results provide a novel family of lead compounds for the discovery of anti-NAFLD candidates.

ObjectiveTo investigate effect of conducting training of autism spectrum disorder （ASD） early screening skill on improving the ability to early identify ASD of medical staffs in primary care hospitals. MethodsIn September 2021， the training of ASD early screening skills was carried out for medical staffs from 20 primary care hospitals in Chengdu. After training， the training effect was evaluated. The numbers of referrals from primary care hospitals to superior hospitals， confirmed ASD as well as their average diagnostic age of children with ASD before and after training were used as evaluation indicators. ResultsAfter training， the number of children with suspected ASD referred by primary care hospitals was more than that before training ［（16.65±11.60） vs. （3.40±2.23）， t=5.431， P<0.01］， the number of children diagnosed with ASD was more than that before training［（6.85±4.93） vs. （2.45±1.67）， t=4.171， P<0.01］， and the differences were statistically significant. As for the diagnosed age of ASD children， after training， the average age was lower than that before training ［（34.95±11.67） vs. （42.2±14.64）， t=-2.553， P=0.019］. ConclusionTraining of ASD early screening skills for medical staffs in primary care hospitals may help to improve their ability to early screening ASD children.