This article systematically reviews the current research status as well as diagnosis and treatment strategies of traditional Chinese medicine （TCM） for gastroesophageal reflux disease （GERD）. Studies demonstrate that TCM， based on the "disease-syndrome combination" approach， exhibits multi-target advantages in alleviating symptoms of various GERD subtypes， promoting mucosal repair， regulating emotions， and facilitating the reduction of western medication. To address clinical challenges such as symptom overlap and limited therapeutic efficacy， strategies have been proposed including "treating different diseases with the same method" and integrated regulation based on viscera correlation. Future efforts should focus on elucidating the mechanisms of compound prescriptions， promoting TCM drug development under the "three-combination" evaluation framework that integrates TCM theory， human experience and clinical trial evidence， and optimizing integrated traditional and western medicine models to enhance GERD management.

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

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

Methods: Motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs) were recorded in 48 patients with TOLF (hybrid 20 vs. en bloc 28) during surgery. Patients were categorized based on MEP/SEP improvement, deterioration, or no change, and MEP/SEP improvement rates were measured in the improvement group. Furthermore, all patients were assessed using the Ashworth and modified Japanese Orthopedic Association scores. Results: The incidences of both MEP/SEP improvement (21.4% vs. 25.0%, p=0.772) and deterioration (21.4% vs. 20.0%, p=0.904) were similar between the en bloc and hybrid laminectomy groups, and no difference in preoperative and postoperative clinical assessments was observed between the two groups (p>0.05). In four patients (4/28, 14.3%) undergoing en bloc laminectomy, MEP amplitudes initially increased after OLF removal but gradually decreased. This delayed MEP reduction did not occur in the hybrid laminectomy group. Furthermore, more patients undergoing en bloc laminectomy had CFL than those undergoing hybrid laminectomy (46.4% vs. 15.0%, p=0.023). In the improvement group, the hybrid laminectomy group exhibited higher MEP improvement rates in the bilateral abductor hallucis than the en bloc laminectomy group (left side: 213.4%±35.9% vs. 152.5%±41.0%, p=0.028; right side: 201.2%±32.0% vs. 145.2%±46.3%, p=0.043). Conclusions Compared with en bloc laminectomy, hybrid laminectomy may be a safe and effective method for treating multilevel TOLF, potentially reducing intraoperative spinal cord irritation and CFL and causing relatively better functional recovery.

Methods: Motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs) were recorded in 48 patients with TOLF (hybrid 20 vs. en bloc 28) during surgery. Patients were categorized based on MEP/SEP improvement, deterioration, or no change, and MEP/SEP improvement rates were measured in the improvement group. Furthermore, all patients were assessed using the Ashworth and modified Japanese Orthopedic Association scores. Results: The incidences of both MEP/SEP improvement (21.4% vs. 25.0%, p=0.772) and deterioration (21.4% vs. 20.0%, p=0.904) were similar between the en bloc and hybrid laminectomy groups, and no difference in preoperative and postoperative clinical assessments was observed between the two groups (p>0.05). In four patients (4/28, 14.3%) undergoing en bloc laminectomy, MEP amplitudes initially increased after OLF removal but gradually decreased. This delayed MEP reduction did not occur in the hybrid laminectomy group. Furthermore, more patients undergoing en bloc laminectomy had CFL than those undergoing hybrid laminectomy (46.4% vs. 15.0%, p=0.023). In the improvement group, the hybrid laminectomy group exhibited higher MEP improvement rates in the bilateral abductor hallucis than the en bloc laminectomy group (left side: 213.4%±35.9% vs. 152.5%±41.0%, p=0.028; right side: 201.2%±32.0% vs. 145.2%±46.3%, p=0.043). Conclusions Compared with en bloc laminectomy, hybrid laminectomy may be a safe and effective method for treating multilevel TOLF, potentially reducing intraoperative spinal cord irritation and CFL and causing relatively better functional recovery.

ObjectiveTo evaluate the pharmacological effect of Buzhong Yiqitang on brain development in offspring of rats with subclinical hypothyroidism （SCH） during pregnancy and explore its potential mechanism. MethodsForty-eight SPF female SD rats were divided into sham operation group （n=8） and model group （n=40）. The rat model of subclinical hypothyroidism （SCH） was constructed by total thyroidectomy combined with postoperative subcutaneous injection of levothyroxine （L-T₄）. The modeled rats were randomly allocated into model， low-， medium-， and high-dose （5.58， 11.16， 22.32 g∙kg^-1， respectively） Buzhong Yiqitang， and euthyrox （4.5×10^-6 g∙kg^-1） groups， with 8 rats in each group. These rats were co-housed with normal male rats for mating. Drug administration started 2 weeks before pregnancy and continued until delivery. Hematoxylin-eosin staining and Golgi-cox staining were used to observe pathological changes in the hippocampal tissue of offspring rats. Western blot was employed to detect the effects of Buzhong Yiqitang on the protein levels of cytochrome C oxidase subunitⅠ （COX）Ⅰ and COXⅣ in the hippocampal tissue of offspring rats. A colorimetric method was used to measure the mitochondrial adenosine triphosphate （ATP） content in the hippocampal tissue of offspring rats. For in vitro experiments， a hydrogen peroxide （H₂O₂）-induced oxidative damage model was established with rat pheochromocytoma cells （PC12）. Interventions included the DNA methyltransferase inhibitor （SGI-1027）， Buzhong Yiqitang-medicated serum， and euthyrox-medicated serum. The cell counting kit-8 （CCK-8） assay was used to examine the effect of Buzhong Yiqitang on cell proliferation. Immunofluorescence staining was performed to evaluate the effect on tubulin beta 3 class Ⅲ （TUBB3） in PC12 cells. Western blot was employed to assess the effects on the protein levels of DNA methyltransferases （TETs and DNMTs） in PC12 cells. The fluorescent probe 2′，7′-dichlorodihydrofluorescein diacetate （DCFH-DA）， luciferase assay， and JC-1 staining were employed to assess the effects of Buzhong Yiqitang on the levels of reactive oxygen species （ROS） and ATP and the mitochondrial membrane potential in PC12 cells. ResultsCompared with the sham group， the model group showed a reduction in the number of hippocampal neurons， incomplete pyramidal cell bodies， loose arrangement， shortened average dendrite length， decreased dendritic complexity and dendritic spine density， and reduced expression levels of COXⅠ and COXⅣ and content of ATP in the brain tissue （P<0.05， P<0.01）. Compared with the model group， after administration of Buzhong Yiqitang and euthyrox， hippocampal neurons exhibited regular arrangement， complete morphology， extended dendrite， increased dendritic complexity and dendritic spine density， and restored expression levels of COXⅠ and COXⅣ and content of ATP （P<0.05， P<0.01）， with the medium-dose Buzhong Yiqitang group showing the best therapeutic effect. In the PC12 cell model of oxidative damage， Buzhong Yiqitang increased the cell viability （P<0.01）， enhanced neuronal differentiation， down-regulated the expression levels of DNMTs （P<0.05）， up-regulated the expression levels of TETs （P<0.05）， decreased the ROS content （P<0.01）， and restored the ATP content and mitochondrial membrane potential （P<0.01）. ConclusionBuzhong Yiqitang protects brain development in offspring of pregnant rats with SCH. It mainly acts on the oxidative stress and mitochondrial dysfunction resulted from abnormal mtDNA methylation， with DNMTs and TETs as the key proteins for its effects.

Methods: Motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs) were recorded in 48 patients with TOLF (hybrid 20 vs. en bloc 28) during surgery. Patients were categorized based on MEP/SEP improvement, deterioration, or no change, and MEP/SEP improvement rates were measured in the improvement group. Furthermore, all patients were assessed using the Ashworth and modified Japanese Orthopedic Association scores. Results: The incidences of both MEP/SEP improvement (21.4% vs. 25.0%, p=0.772) and deterioration (21.4% vs. 20.0%, p=0.904) were similar between the en bloc and hybrid laminectomy groups, and no difference in preoperative and postoperative clinical assessments was observed between the two groups (p>0.05). In four patients (4/28, 14.3%) undergoing en bloc laminectomy, MEP amplitudes initially increased after OLF removal but gradually decreased. This delayed MEP reduction did not occur in the hybrid laminectomy group. Furthermore, more patients undergoing en bloc laminectomy had CFL than those undergoing hybrid laminectomy (46.4% vs. 15.0%, p=0.023). In the improvement group, the hybrid laminectomy group exhibited higher MEP improvement rates in the bilateral abductor hallucis than the en bloc laminectomy group (left side: 213.4%±35.9% vs. 152.5%±41.0%, p=0.028; right side: 201.2%±32.0% vs. 145.2%±46.3%, p=0.043). Conclusions Compared with en bloc laminectomy, hybrid laminectomy may be a safe and effective method for treating multilevel TOLF, potentially reducing intraoperative spinal cord irritation and CFL and causing relatively better functional recovery.

Objective To explore the role and mechanism of RNA m6A methyltransferase Wilms'tumor 1-associated protein(WTAP)in epithelial-mesenchymal transition(EMT)of glioblastoma cells and its association with transcription factor JUNB.Methods(1)Based on the Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases,the expression levels of transforming growth factor β(TGF-β),WTAP,and JUNB in glioblastoma multiforme(GBM)and normal brain tissues were analyzed,as well as their diagnostic and prognostic values for GBM.The correlation of TGF-β,WTAP,and JUNB with gliomas of different WHO grades was analyzed using the Chinese Glioma Genome Atlas(CGGA)database.Spearman correlation analysis was performed to assess the correlation between TGF-β and m6A methyltransferases.(2)An EMT model was established in human astrocytoma U87-MG cells through TGF-β1 induction.qRT-PCR and Western blotting were employed to detect the expression levels of WTAP,JUNB,matrix metalloproteinase 2(MMP2),and N-cadherin.The migration capacity of U87-MG cells was evaluated by wound-healing and Transwell assays.An m6A RNA methylation quantification kit(colorimetric)was used to detect RNA m6A methylation modification levels.A stable cell line with low expression of WTAP was constructed to investigate the effects of WTAP knockdown on the migration ability of U87-MG cells,as well as the expression of JUNB.(3)A protein-protein interaction network was constructed using STRING database and GeneMANIA database,followed by gene ontology(GO)and KEGG pathway enrichment analyses to explore the biological processes,molecular functions,cellular components,and signaling pathways potentially involved in TGF-β/WTAP/JUNB.Gene set enrichment analysis(GSEA)was performed on JUNB-related genes to investigate their potential downstream signaling pathways.Results(1)The expression levels of TGF-β,WTAP,and JUNB were significantly higher in GBM(P<0.001),positively correlated with WHO grades of glioma(P<0.001).Glioma patients with high expression of all three genes had shorter overall and disease-free survival(P<0.001).Spearman analysis showed that the expression of TGF-β in GBM was positively correlated with WTAP(r=0.175,P=0.023),but no significant correlation with other m6A methyltransferases(P>0.05).(2)After TGF-β1 treatment,the level of m6A methylation modification of total RNA in U87-MG cells significantly increased(P<0.001).Wound-healing assay and Transwell assay results showed that the migration ability of U87-MG cells was significantly increased after TGF-β1 treatment(P<0.01),while WTAP knockdown significantly reduced the migration ability of U87-MG cells(P<0.01).qRT-PCR and Western blotting results showed that the mRNA and protein expression levels of WTAP,N-Cadherin,MMP2,and JUNB in U87-MG cells were significantly increased after 48 h of TGF-β1 induction(P<0.001),while WTAP knockdown significantly reduced the mRNA and protein expression of JUNB(P<0.001).(3)The TGF-β/WTAP/JUNB-related protein-protein interaction network was constructed,which was primary involved in mRNA modification and EMT.GSEA results showed that JUNB-related signaling pathways were closely associated with glioma malignant progression.Conclusions TGF-β,WTAP,and JUNB are all associated with GBM malignant progression and poor patient prognosis.TGF-β may enhance total RNA m6A modification by promoting the expression of m6A methyltransferase WTAP,and WTAP subsquentaly upregulates transcription factor JUNB,thereby promoting EMT and malignant progression of GBM.

Objectives:To explore the value of non-invasive myocardial work combined with myocardial contrast echocardiography(MCE)in the early diagnosis of coronary artery disease and its efficacy in stratifying the severity of coronary vessel lesions.Methods:A total of 130 patients with suspected coronary artery disease admitted to the First Affiliated Hospital of Dalian Medical University from June 2024 to January 2025 were enrolled in this study.All patients underwent echocardiography and MCE after admission,and coronary angiography(CAG).Based on CAG results,patients were divided into non-CAD group(n=45,coronary artery stenosis<50%)and CAD group(n=85,coronary artery stenosis≥50%).Patients in CAD group were further divided into low-score CAD group(≤49 points,n=43)and high-score CAD group(>49 points,n=42)according to the median of Gensini score(49 points).Non-invasive MW indices and quantitative MCE parameters were assessed.A binary logistic regression model was used to construct a combined diagnostic model,and the value of each parameter in diagnosing CAD and evaluating the severity of coronary lesions was calculated.The receiver operating characteristic(ROC)curve of subjects was estimated,and the area under the curve(AUC)was calculated to evaluate its sensitivity and specificity for early diagnosis of coronary heart disease.Results:Compared with the non-CAD group,the global longitudinal strain,global work index(GWI),and global constructive work(GCW)in both low-score and high-score CAD groups were significantly lower(all P<0.05),and the global work efficiency in the high-score CAD group was significantly reduced(P<0.05).MCE indices in both low-score and high-score CAD groups were significantly lower than those in the non-CAD group(all P<0.05).The multivariate logistic stepwise regression analysis and ROC curve showed that GWI(OR=0.997,95%CI:0.995-0.999,P=0.003)and A value(representing the peak intensity of the curve,reflecting myocardial blood volume(OR=0.415,95%CI:0.246-0.698,P=0.001)were independent predictors of low-score CAD.The combined diagnostic sensitivity and specificity for low-score coronary artery disease were 72.1%and 88.9%respectively,with an AUC of 0.851.GCW(OR=0.997,95%CI:0.995-1.000,P=0.019)and β-value(OR=0.000,95%CI:0.000-0.003,P<0.001)were independent predictors of high-score CAD.The combined diagnostic sensitivity and specificity for high-score coronary artery disease were 88.1%and 88.9%respectively,with an AUC of 0.934.Conclusions:Both non-invasive myocardial work parameters and MCE parameters have high diagnostic efficacy for coronary artery lesions of various degrees.The combined application of the two methods significantly improves the accuracy of coronary artery disease diagnosis,with improved sensitivity and specificity than single technique.Our results provide a new non-invasive comprehensive diagnostic model for clinical early diagnosis and risk stratification of coronary artery disease.

Investigated the mechanisms by which baicalein regulates nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)to ameliorate lipopolysaccharide(LPS)-induced sepsis-asso-ciated acute kidney injury(AKI)in mice.Sixty male C57BL/6 mice were randomly divided into six groups:control,model,low-dose baicalein(50 mg/kg),medium-dose baicalein(100 mg/kg),high-dose baicalein(200 mg/kg),and high-dose baicalein+brusatol(4 mg/kg).Baicalein was adminis-tered orally for 7 days as a preventative measure.Sepsis was induced via intraperitoneal injection of LPS.Murine sepsis score(MSS)was assessed within 12 hours post-induction.Serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an automatic biochemical analyzer and enzyme-linked immunosorbent assays(ELISA),respectively.Histopathological changes in kidney tissues were ob-served via hematoxylin-eosin(HE)staining.Western blot analysis was employed to determine the protein expression levels of Nrf2,HO-1,caspase-8,TNF-α,IL-1β,and IL-6 in kidney tissues.Additionally,total superoxide dismutase(SOD)activity in kidney tissues was assessed using com-mercially available kits.Compared to the model group,baicalein treatment significantly improved renal histopathological changes,alleviated cellular damage,and reduced the levels of inflammatory cytokines(TNF-α,IL-1βand IL-6)(P＜0.01)and kidney injury markers(Scr and BUN)(P＜0.01).Moreover,baicalein treatment significantly increased the protein expression levels of Nrf2 and HO-1(P＜0.01)and enhanced antioxidant enzyme activity.In conclusion,baicalein may pro-tect against LPS-induced sepsis-associated AK1 in mice by modulating the Nrf2/HO-1 signaling pathway,thereby attenuating oxidative stress,reducing inflammation,and disrupting the vicious cycle between inflammation and oxidative stress.