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

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

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 This study aimed to explore the potential targets of Yishenqingli Formula in treating idiopathic membranous nephropathy(IMN)using a combination of liquid chromatography-mass spectrometry(LC-MS)analysis and network pharmacology.Methods The active ingredients of the Yishen Qingli Formula were identified through the BATMAN-TCM database and LC-MS qualitative analysis.The biological processes and mechanism pathways of the Yishen Qingli Formula in treating IMN were predicted using network pharmacology,and molecular docking and in vitro,experiments were conducted to verify the selected core targets.The core targets were selected and validated through molecular docking and in vitro experiments.Results A total of 15 active ingredients were selected from the Yishen Qingli Formula,and 72 core genes were obtained by intersecting its target with the IMN disease target.GO enrichment analysis results showed that the regulation of apoptosis signaling pathway,white cell migration,peptide tyrosine phosphorylation,and so on were involved;The KEGG pathway enrichment analysis results showed that the treatment of IMN with Yishen Qingli Formula involves apoptosis-related signaling pathways such as TNF,PI3K/AKT,MAPK,etc.In vitro,experiments have shown that Yishen Qingli Formula can reduce podocyte apoptosis by regulating the PI3K/AKT pathway.Conclusion Yishen Qingli Formula is a treatment for idiopathic membranous nephropathy through multiple targets and pathways.It has an anti-apoptotic effect on the C5b-9 induced podocyte sub-lysis model,and its mechanism of action may be related to the TNF,PI3K/AKT,MAPK signaling pathways.

The relationship between exercise and cardiac health has always been a hotspot in the fields of medicine and exercise science. Recently, with the in-depth study of the biological clock, people have gradually realized the close relationship between cardiac metabolic activity and circadian rhythms. The mammalian circadian system includes the central circadian clock and peripheral circadian clocks, the central circadian clock is the main clock system responsible for regulating the circadian rhythms in organisms, located in the suprachiasmatic nucleus (SCN) of the hypothalamus in mammals, which receives light signals from the retina and translates them into neural signals to regulate peripheral circadian clocks distributed throughout the body. Peripheral circadian clocks exist in various tissues and organs of organisms, coordinating with the central circadian clock to maintain the circadian rhythms of the organism. A series of clock genes regulate downstream clock-controlled genes through the transcriptional-translational feedback loop (TTFL), profoundly affecting the physiological activities of the heart, including cardiac contraction, relaxation, and metabolic processes. Factors such as sleep disorders, shift work, light pollution, and excessive use of electronic devices in modern lifestyles have led to widespread disruption of circadian rhythms, which are significantly correlated with increased cardiovascular disease incidence and mortality. Studies have found that dysregulation of the cardiac circadian clock can not only lead to myocardial lipid degeneration and weakened metabolic rhythms but also decrease myocardial glucose utilization, thereby increasing the risk of adverse cardiac events. Exercise, as a key zeitgeber, has been widely demonstrated to regulate the circadian clocks of peripheral organs such as skeletal muscle, kidneys, and liver. Additionally, exercise, as an important means to improve cardiovascular function, can effectively enhance cardiac metabolic function and resistance to stress stimuli, playing a significant role in promoting heart health. However, the specific mechanisms by which exercise affects the cardiac circadian clock and its related genes are currently unclear. Therefore, this review will focus on the relationship between the cardiac circadian clock and cardiac metabolic activity, summarize previous research to review the possible mechanisms of exercise-mediated regulation of cardiac metabolic activity on the cardiac circadian clock. The cardiac circadian clock plays an important role in maintaining cardiac metabolic activity and physiological functions. The loss of cardiac circadian clock genes Bmal1 and Clock can significantly reduce cardiac fatty acid and glucose utilization rates, increase myocardial lipotoxicity, weaken the circadian rhythm of myocardial triglyceride metabolism, and lead to abnormalities in the circadian clocks of other peripheral organs. Exercise, as a zeitgeber, can independently regulate the cardiac circadian clock apart from the central circadian clock. Additionally, exercise, as an important means to improve cardiovascular function, may regulate cardiac metabolic activity and the transcription of clock genes by activating the hypothalamic-pituitary-adrenal axis (HPA) and sympathetic-adrenal-medullary axis (SAM) and regulating energy metabolism, thereby maintaining the stability of the cardiac circadian clock and promoting heart health. Future research on the molecular mechanisms of exercise regulation of the cardiac circadian clock will help clarify the role and impact of clock genes in cardiac metabolism and physiological activities, providing new preventive and treatment strategies for shift workers, night owls, and patients with cardiovascular diseases. Therefore, future research should focus on (1) the mechanisms by which exercise regulates cardiac metabolic activity and the circadian clock, (2) the effects and mechanisms of exercise on the disruption of cardiac circadian clock induced by light-dark cycle disturbances, and (3) the effects of exercise on the metabolic activity and circadian rhythms of other peripheral organs regulated by the cardiac circadian clock.

The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological status. These intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis, metabolism, and immune response. The disruption of microbiota, known as dysbiosis, has been implicated in many intestinal diseases, including colorectal cancer (CRC). As the third most common cancer and the second leading cause of cancer-related death worldwide, CRC poses a significant health burden. There is an urgent need for novel interventions to reduce CRC incidence and improve clinical outcomes. Modulating the intestinal microbiota has emerged as a promising approach for CRC prevention and treatment. Current research efforts in CRC probiotics primarily focus on reducing the incidence of CRC, alleviating treatment-related side effects, and potentiating the efficacy of anticancer therapy, which is the key to successful translation to clinical practice. This paper aims to review the traditional probiotics and new interventions, such as next-generation probiotics and postbiotics, in the context of CRC. The underlying mechanisms of probiotic anti-cancer effects are also discussed, including the restoration of microbial composition, reinforcement of gut barrier integrity, induction of cancer cell apoptosis, inactivation of carcinogens, and modulation of host immune response. This paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and immunotherapy. Despite all the promising findings presented in studies, the evaluation of potential risks, optimization of delivery methods, and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.

Objective:To examine the application of a novel pedagogical approach multidimensional supportive psychological intervention(MSPI)in the clinical practice teaching of andrological nursing care.Methods:Using the Hamilton Depression Scale(HAMD),we assessed the psychology of 100 nursing interns about to enter clinical practice in the Department of Andrology from De-cember 2021 to December 2022.We equally randomized the subjects into an experimental and a control group,the former receiving MSPI and the latter trained on the conventional teaching model without any psychological support intervention.Results:Compared with the baseline,the HAMD scores were significantly decreased in the experimental group after intervention(12.4±2.1 vs 8.9±2.4,P＜0.01),but increased in the controls(13.1±1.8 vs 14.7±1.9,P＜0.01);the skill scores dramatically increased in the experimental group(82.6±4.7 vs 91.2±2.4,P＜0.01),but decreased in the control group after intervention(81.0±3.5 vs 80.4±2.7,P=0.28).Conclusion:MSPI can significantly enhance the learning enthusiasm of nursing students in a short period,re-duce their psychological stress and improve teaching outcomes.This approach,combining psychology with teaching,can also strength-en the mental resilience of nursing students and better confront them with future professional challenges.

Limosilactobacillus reuteri is a microbe intricately linked to humans and animal health.A thor-ough assessment of its safety and potential benefits is imperative prior to its application in human and ani-mals.In this investigation,we performed a comprehensive analysis encompassing genome sequencing,genomic analysis,and phenotypic characterization of L.reuteri Q35,an exceptionally proficient producer of reuterin.The whole genome sequencing results showed that the complete genome sequence spans 2145158 bp with a GC content of 38.9％ and encompasses 2121 genes.Initial identification of antibiotic-re-sistant genes,virulence factors,and toxin-coding genes in the genome substantiated the strain' s low-risk status.Subsequent tests for antibiotic resistance,acute oral toxicology,and hemolysis further confirmed its elevated safety level.The genome of L.reuteri Q35 was found to contain genes associated with adhe-sion and stress tolerance.Following exposure to artificial gastric juice and bile salt,the strain exhibited a higher survival rate and demonstrated a strong scavenging ability for hydroxyl free radicals in antioxidant capacity tests.These findings suggested that L.reuteri Q35 possesses unique probiotic properties.Addi-tionally,the genome of strain Q35 harbors three truncated oxaloyl-CoA decarboxylase genes (oxc1,oxc2 and oxc3),overexpression of which resulted in a significant increase in ammonium oxalate degradation from 29.5％ to 48.8％.These findings highlight that L.reuteri Q35 exhibits both favorable safety charac-teristics alongside beneficial properties,making it a promising candidate for treating metabolic disorders such as hyperoxaluria.

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*

The present study investigated the mechanism of artesunate in the treatment of bone destruction in experimental rheumatoid arthritis(RA) based on transcriptomics and network pharmacology. The transcriptome sequencing data of artesunate in the inhibition of osteoclast differentiation were analyzed to obtain differentially expressed genes(DEGs). GraphPad Prism 8 software was used to plot volcano maps and heat maps were plotted through the website of bioinformatics. GeneCards and OMIM were used to collect information on key targets of bone destruction in RA. The DEGs of artesunate in inhibiting osteoclast differentiation and key target genes of bone destruction in RA were intersected by the Venny 2.1.0 platform, and the intersection target genes were analyzed by Gene Ontology(GO)/Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment. Finally, the receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model and collagen-induced arthritis(CIA) model were established. Quantitative real time polymerase chain reaction(q-PCR), immunofluorescence, and immunohistochemistry were used to verify the pharmacological effect and molecular mechanism of artesunate in the treatment of bone destruction in RA. In this study, the RANKL-induced osteoclast differentiation model in vitro was established and intervened with artesunate, and transcriptome sequencing data were analyzed to obtain 744 DEGs of artesunate in inhibiting osteoclast differentiation. A total of 1 291 major target genes of bone destruction in RA were obtained from GeneCards and OMIM. The target genes of artesunate in inhibiting osteoclast differentiation and the target genes of bone destruction in RA were intersected to obtain 61 target genes of artesunate against bone destruction in RA. The intersected target genes were analyzed by GO/KEGG enrichment. According to the results previously reported, the cytokine-cytokine receptor interaction signaling pathway was selected for experimental verification. Artesunate intervention in the RANKL-induced osteoclast differentiation model showed that artesunate inhibited CC chemokine receptor 3(CCR3), CC chemokine receptor 1(CCR1) and leukemia inhibitory factor(LIF) mRNA expression in osteoclasts in a dose-dependent manner compared with the RANKL-induced group. Meanwhile, the results of immunofluorescence and immunohistochemistry showed that artesunate could dose-dependently reduce the expression of CCR3 in osteoclasts and joint tissues of the CIA rat model in vitro. This study indicated that artesunate regulated the CCR3 in the cytokine-cytokine receptor interaction signaling pathway in the treatment of bone destruction in RA and provided a new target gene for the treatment of bone destruction in RA.
Rats ; Animals ; Arthritis, Experimental/drug therapy* ; Artesunate/therapeutic use* ; Arthritis, Rheumatoid/genetics* ; Transcriptome ; Network Pharmacology ; Osteoclasts ; Receptors, Cytokine/therapeutic use*