OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

An analysis of 24 144 norovirus sequences from Asia and Russia deposited in GenBank between 1995 and 2023 was conducted,to understand the temporal and spatial variations in norovirus genotypes in these regions.Norovirus sequences from Asia and Russia were downloaded in FASTA format from GenBank for the years 1995-2023,and analyzed in Excel,R language,and GraphPad Prism for data visualization.The number of norovirus sequences submitted to GenBank increased annually from 2004 and peaked in 2015.Notably,China and Japan contributed 62.3％of all submitted norovirus sequences.These sequences encompassed 31 capsid genotypes(C-type),with GⅠ accounting for 9％and GⅡ accounting for 90％.Additionally,49 polymerase types(P-type)were identified,along with 68 combinations of CP types;among the analyzed recombinant sequences(4 460 entries in total),approxi-mately 41％belonged to three predominant recombinant strains:GⅡ.2[P16],GⅡ.4[P31],and GⅡ.4[P16].This analysis provides valuable insights into the distribution characteristics of norovirus genotypes across Asia and Russia over time,thereby supporting vac-cine design and evaluation efforts.

Objective:To investigate the predictive value of measured cardiac power output(CPO)of echocardiography for the prognosis of elderly patients with acute heart failure(AHF)in the vulnerable period of heart failure.Methods:A total of 120 elderly patients with AHF who admitted to the Third Hospital Affiliated to Shanxi Medical University from January 2021 to January 2024 were selected,and they were divided into the major adverse cardiovascular events(MACE)group(18 cases)and the non-MACE group(102 cases)according to whether occurred MACE in the vulnerable period within 3 months after discharge.The baseline data of the two groups of patients were compared.Logistic regression was used to analyze the influencing factors of occurring MACE in the vulnerable period of patients,and the receiver operating characteristic(ROC)curve was used to analyze the predictive value of CPO for MACE in the vulnerable period of heart failure in elderly patients with AHF.Results:In the baseline data of patients,the total cholesterol,25-hydroxyvitamin D[25(OH)D],reserve CPO,resting CPO,and peak CPO in the MACE group were all lower than those in the non-MACE group,and the differences were statistically significant(t=5.987,2.236,2.921,2.390,4.569,P<0.05).The levels of brain natriuretic peptide(BNP)and N-terminal pro-brain natriuretic peptide(NT-proBNP)in the MACE group were higher than those in the non-MACE group,and the differences were statistically significant(t=22.074,23.368,P<0.05).The results of Logistic regression analysis showed that the total cholesterol,25(OH)D,reserve CPO,resting CPO,and peak CPO were all influencing factors for the occurrence of MACE during the vulnerable period of heart failure in patients(OR=0.064,0.942,0.015,0.035,0.041,P<0.05).ROC curve analysis showed that the efficacy of resting CPO and reserve CPO of the cardiac function indicators in predicting MACE of patients were slightly lower than that of peak CPO.The AUC,sensitivity and specificity of peak CPO in predicting MACE of patients were 0.752,92.2%and 55.6%,respectively.Conclusion:The lower peak CPO value of cardiac function indicator of echocardiography is independent risk factor for MACE during the vulnerable period of heart failure in elderly patients with AHF.Measuring CPO can identify potential poor prognosis populations in advance.

Aim To explore the relevant mechanisms of isoliquiritigenin(ISL)in inhibiting the proliferation and migration of vascular smooth muscle cells(VSMCs)by regulating the GRB2/ERK signaling pathway.Methods Human primary vascular smooth muscle cells(hVSMCs)were cultured,and stimulated with different concentrations of ISL and fixed concen-trations of growth factors PDGF-BB and EGF,respec-tively.Subsequently,the effect of overexpressing GRB2 on the efficacy of ISL was observed.CCK-8 assay was used to detect cell proliferation;BrdU assay was used to detect DNA synthesis;Western blot was used to de-tect the expression levels of OPN,ICAM-1,VCAM-1,GRB2,ERK1/2,and p-ERK1/2;wound healing assay was used to detect cell migration;transwell assay was used to detect cell invasion.Results Compared with the blank control group and the ISL 20 mg·L-1 group,the PDGF-BB group and the EGF group showed increased cell viability and DNA synthesis,decreased cell migration distance,and increased number of inva-sive cells.Additionally,the expression levels of GRB2 and p-ERK1/2 increased.Compared with the PDGF-BB 40 μg·L-1group or the EGF 10 mg·L-1 group,the ISL drug intervention group showed decreased cell viability and DNA synthesis,increased migration dis-tance of cells,decreased number of invasive cells,and decreased expression levels of GRB2 and p-ERK1/2.Compared with the ISL 20 mg·L-1+PDGF-BB and ISL 20 mg·L-1+EGF groups,the groups with ISL+PDGF-BB+pcDNA-GRB2 group and ISL+EGF+pcDNA-GRB2 group showed increased expression lev-els of GRB2,p-ERK1/2,OPN,ICAM-1,and VCAM-1,increased cell viability and DNA synthesis,decreased migration distance,and increased number of invasive cells.Compared with the ISL+PDGF-BB+pcDNA-GRB2 group and the ISL+EGF+pcDNA-GRB2 group,the pcDNA-GRB2+PDGF-BB group or the pcDNA-GRB2+EGF group showed increased expres-sion levels of GRB2,p-ERK1/2,OPN,ICAM-1,and VCAM-1,increased cell viability and DNA synthesis,decreased migration distance,and increased number of invasive cells.Conclusions Isoliquiritigenin inhibits the proliferation and migration of vascular smooth mus-cle cells by regulating the GRB2/ERK signaling path-way.

Objective To investigate the role of Insulin like growth factor 2 mRNA binding protein 1(IGF2BP1)and long non-coding RNA LINC00160(LINC00160)in gastric cancer,and its potential mechanism of regulating the proliferation and invasion of gastric cancer cells.Methods Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the expression level of LINC00160 in gastric cancer tissues and cells.Bioinformatics prediction,RNA-binding protein immunoprecipitation(RIP)and methylated RNA immunoprecipitation(MeRIP)were used to verify the binding effect of LINC00160 and IGF2BP1.The correlation between the expression of LINC00160 and IGF2BP1 in gastric cancer tissues was analyzed by Pearson assay.CCK-8 assay and Transwell assay were used to detect cell proliferation and invasion.The changes of aerobic glycolysis index[glucose intake,lactate production,and Adenosine-triphosphate(ATP),extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)]were detected and analyzed.Results Compared with normal tissues,the expression of LINC00160 in gastric cancer tissues(5.13±0.62 vs 1.02±0.03)was significantly up-regulated,and the difference was statistically significant(t=-36.266,P<0.001).The expression level of LINC00160 in gastric cancer cells was higher than that of human normal gastric epithelial cell line GES-1,and the difference was statistically significant(F=24.595,P<0.001).Compared with the control group,silenting LINC00160 significantly inhibited the proliferation(0.42±0.03 vs 1.03±0.04)and invasion(22.13%±1.97%vs 42.15%±2.67%)of AGS cells,decreased glucose uptake(2.11±0.26mmol/L vs 4.22±0.37mmol/L)and lactate production(6.84±1.25mmol/L vs 11.68±1.55mmol/L),decreased ECAR,and increased ATP(3.34±0.29mmol/L vs 1.87±0.24mmol/L)levels and OCR,and the differences were statistically significant(t=4.188～24.423,all P<0.01).The expression of IGF2BP1 protein in gastric cancer tissues(4.07±0.36)was significantly higher than that in adjacent tissues(1.01±0.03),and the difference was statistically significant(t=-46.396,P<0.01),and was positively correlated with the expression of LINC00160(r2=0.774 5,P<0.01).Mechanistic studies revealed that IGF2BP1 upregulated LINC00160 expression by binding m6A modified LINC00160 to promote its stability.Silencing IGF2BP1 significantly inhibited the expression of LINC00160 and the proliferation,invasion and aerobic glycolysis of gastric cancer cells,and the differences were statistically significant(t=4.386～11.989,all P<0.01).Overexpression of LINC00160 reversed the effect of IGF2BP1 silencing on AGS cells.Conclusion LINC00160 is significantly up-regulated in gastric cancer,and IGF2BP1 may stably regulate the expression of LINC00160 through m6A modification,promote the aerobic glycolysis of tumor cells,and participate in the occurrence and development of gastric cancer.

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

OBJECTIVE: This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues. METHODS: Chronic unpredictable mild stress model-a classic depression rat model-was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of "behavior-brain energy metabolism-intestinal energy metabolism" of depression. RESULTS: XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na⁺-K⁺-adenosine triphosphatase (ATPase) and Ca²⁺-Mg²⁺-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine. CONCLUSION XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases. Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. J Integr Med. 2025; 23(6):706-720.
Animals ; Energy Metabolism/drug effects* ; Antidepressive Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Brain/drug effects* ; Male ; Depression/metabolism* ; Rats ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Hippocampus/drug effects*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To compare the efficacy between slanted bilateral lateral rectus recession(S-BLR)and conventional bilateral lateral recession(C-BLR)procedure in the treatment of convergence insuffi-ciency-type intermittent exotropia.Methods Relevant studies published before November 2023 were systematically searched in PubMed,Cochrane Library,EmBase,Web of Science,CNKI,Wanfang and VIP databases to compare the surgical effects of S-BLR and C-BLR,expressed by OR value and 95%CI.The success rate,recurrence rate,overcor-rection rate and stereoscopic improvement rate were analyzed by random effects model.Results A total of 5 studies involving 296 patients were included in the analysis.The success rate of the S-BLR procedure was significantly higher than that of C-BLR(OR=4.06,95%CI:2.47-6.67,P＜0.001),patients subjected to the C-BLR pro-cedure were more likely to be recurrent(OR=0.21,95%CI:0.08-0.52,P＜0.001).No statistically signifi-cant differences in the combined results for overcorrection rates(OR=0.43,95%CI:0.07-2.52,P=0.35)and stereoscopic improvement rates(OR=0.82,95%CI:0.36-1.83,P=0.62)were present between the S-BLR and C-BLR procedures(P＞0.05).Conclusion S-BLR procedure has a higher success rate and a lower recurrence rate in patients with aggregation-deficient intermittent exotropia.