Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

ObjectiveTo observe the effect of Huayu Mingmu prescription on retinal angiogenesis and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）-hypoxia inducible factor-1α/vascular endothelial growth factor A （HIF-1α/VEGFA） signaling pathway in diabetic retinopathy （DR） rats. MethodsSixty-four SPF-grade male SD rats were used in the study. Eleven rats were randomly selected as the normal group， while the remaining 53 rats were fed a high-sugar， high-fat diet combined with low-dose streptozotocin （STZ） intraperitoneal injection to establish a type 2 diabetes mellitus （T2DM） rat model. DR model evaluation was performed after 12 weeks of diabetes. The rats were then divided into model， low-dose， medium-dose， and high-dose groups of Huayu Mingmu prescription （9.29， 18.57， 37.14 g·kg^-1）， and a calcium dobesilate group （0.16 g·kg^-1）， with 10 rats in each group. The rats were orally administered the corresponding doses of Huayu Mingmu prescription and calcium dobesilate. The normal and model groups received equal volumes of physiological saline via gavage for 8 consecutive weeks. Retinal vascular changes were observed through fundus photography， and pathological changes in retinal tissue were evaluated using hematoxylin-eosin （HE） staining. Retinal microvascular pathological changes were examined through retinal vascular network preparation and periodic acid-Schiff （PAS） staining. Immunofluorescence （IF） was used to detect the expression of VEGFA and angiopoietin-2 （Ang-2） in retinal tissue. Western blot was employed to detect the protein expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. ResultsCompared with the normal group， the model group exhibited significant pathological changes in retinal tissue， including the appearance of acellular capillaries， as well as significant endothelial cell （E） proliferation and pericyte （P） loss （P<0.01）. The E/P was significantly elevated （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly increased （P<0.01）， and the expression of Ang-2 protein was significantly elevated （P<0.01）. In contrast， retinal tissue in the treatment groups showed alleviated pathological changes， with reduced endothelial cell proliferation and pericyte loss （P<0.05， P<0.01）. Among the treatment groups， the high-dose Huayu Mingmu prescription and the calcium dobesilate group exhibited a decreased E/P （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly reduced （P<0.05， P<0.01）， and the expression of Ang-2 protein was significantly decreased （P<0.01）. ConclusionHuayu Mingmu prescription can intervene in retinal neovascularization in DR rats， delay the progression of DR， and its mechanism may be related to antagonizing the PI3K/Akt/mTOR-HIF-1α/VEGFA signaling pathway.

ObjectiveTo observe the clinical efficacy of modified Jinwei Guben Decoction （金卫固本汤， MJGD） combined with Bailing Capsule （百令胶囊， BC） in the treatment of chronic obstructive pulmonary disease （COPD） patients in the stable stage with qi deficiency， blood stasis and phlegm obstruction syndrome， in addition to conventional western medicine treatment. MethodsA total of 102 patients with stable COPD and qi deficiency， blood stasis， and phlegm obstruction syndrome were included in the study. According to the patients'preferences， they were divided into treatment group （49 cases） and control group （53 cases）. The control group received conventional western medicine treatment， while the treatment group was given MJGD （1 dose daily） combined with BC （2.0 g each time， three times a day） additionally. The treatment period was 3 months， and the patients were followed up for 1 year after the treatment. The acute exacerbation frequency （mild， moderate， severe） before treatment， during treatment， at 6-month follow-up， and at 1-year follow-up was compared between groups. Additionally， the lung function indicators such as FEV₁， FEV₁%pred， FVC， and FEV₁/FVC ratio， traditional Chinese medicine （TCM） syndrome scores， modified British Medical Research Council （mMRC） dyspnea scale， and the COPD Assessment Test （CAT） scores before and after treatment were compared. A logistic regression model was constructed to analyze the impact of MJGD combined with BC on clinical efficacy. ResultsFour patients dropped out from the treatment group and eight from the control group， leaving 45 patients of each group for statistical analysis. The number of mild and moderate acute exacerbations in the treatment group was lower than that in the control group during the treatment period， at 6-month follow-up and within 1 year of follow-up （P＜0.05） .The number of severe acute exacerbations was only lower in the treatment group than in the control group at 6-month follow-up （P＜0.05）. Compared with that before treatment， the number of acute exacerbations of all degrees in the treatment group was significantly reduced within 1 year of follow-up （P＜0.05），while only the number of mild acute exacerbations in the control group was significantly reduced within 1 year of follow-up （P＜0.05）. The treatment group showed significant improvement in FEV₁ and FEV₁%pred and FEV₁/FEV， while the control group showed a significant decline in FEV₁ and FVC （P＜0.05）. After treatment， both groups showed significant reductions in TCM syndrome scores， including coughing， sputum， wheezing， chest tightness， shortness of breath， and fatigue， as well as mMRC and CAT scores （P＜0.05）， with the treatment group having significantly lower scores than the control group （P＜0.05）. The overall clinical effective rate of in the treatment group was 93.33% （42/45）， significantly higher than that of the control group， 75.56% （34/45， P＜0.05）. Multivariate logistic regression analysis showed that the use of MJGD combined with BC （OR = 4.68， 95%CI： 1.15 - 19.09， P = 0.03） was positively correlated with clinical efficacy. ConclusionsIn addition to conventional western medicine treatment， the combination of MJGD and BC can reduce the frequency of acute exacerbations， delay the decline of lung function， improve clinical symptoms， and significantly enhance the clinical efficacy in patients with stable COPD and qi deficiency， blood stasis， and phlegm obstruction syndrome.

ObjectiveTo study the effect of Jinwei Pingchuan decoction combined with conventional Western medicine on the number of acute exacerbations， lung function， and clinical symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease （COPD） with phlegm-heat obstruction in lung syndrome. MethodsA non-randomized controlled trial was conducted to include 60 patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. Patients were divided into a treatment group and a control group based on whether they received Jinwei Pingchuan decoction， with 30 patients in each group. The treatment group received Jinwei Pingchuan decoction combined with conventional Western medicine therapy， while the control group received conventional Western medicine therapy alone. Both groups received treatment for 7 days. The number of acute exacerbations and lung function indices were followed up and recorded before treatment and three months after treatment. The following outcomes were observed before and after treatment： the number of acute exacerbations， lung function indices （forced expiratory volume in one second ［FEV₁］， percentage of predicted value ［FEV₁%pred］， forced vital capacity ［FVC］， and FEV₁/FVC ratio）， the degree of acute exacerbation， TCM syndrome score， COPD assessment test （CAT） score， modified British Medical Research Council Dyspnea Questionnaire （mMRC） score， C-reactive protein （CRP）， and white blood cell （WBC） count. ResultsAfter 3 months of follow-up， the treatment group showed a significant reduction in the number of acute exacerbations compared with the pre-treatment values （P<0.05）. After treatment， the treatment group had fewer acute exacerbations than the control group （P<0.05）. The degree of acute exacerbation in the treatment group improved significantly compared with the pre-treatment values （P<0.05）. After treatment， the degree of acute exacerbation in the treatment group was improved compared to the control group （P<0.05）. Regarding lung function， FEV₁， FEV₁%pred， FVC， and FEV₁/FVC ratio increased significantly in the treatment group compared with the pre-treatment values （P<0.05）， and similar improvements were observed in the control group （P<0.05）. After treatment， FEV₁ and FVC were higher in the treatment group than the control group （P<0.05）. Regarding TCM syndrome scores， the scores for individual symptoms such as wheezing， cough， expectoration， chest tightness， shortness of breath， and fatigue， as well as the total score， decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）. In the control group， the scores for cough， expectoration， chest tightness， fatigue， and palpitation， as well as the total score， also decreased （P<0.05）. After treatment， the treatment group showed significantly lower scores for wheezing， cough， chest tightness， shortness of breath， and the total score than the control group （P<0.05）. Regarding the CAT score， the scores for cough， expectoration， chest tightness， climbing stairs， going out， activity， and energy， as well as the total score， decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）. In the control group， the scores for cough， expectoration， chest tightness， sleep， energy， and the total score decreased （P<0.05）. After treatment， the treatment group showed significantly lower scores for cough， expectoration， chest tightness， activity， and going out than the control group （P<0.05）. Regarding the mMRC score， CRP level， and WBC count， all these parameters decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）， and similar reductions were observed in the control group （P<0.05）. ConclusionJinwei Pingchuan decoction can reduce the number of acute exacerbations and the degree of acute exacerbation in patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. It also improves lung function and symptoms such as cough and chest tightness， thereby enhancing the quality of life of patients.

ObjectiveTo study the effect of Jinwei Pingchuan decoction combined with conventional Western medicine on the number of acute exacerbations， lung function， and clinical symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease （COPD） with phlegm-heat obstruction in lung syndrome. MethodsA non-randomized controlled trial was conducted to include 60 patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. Patients were divided into a treatment group and a control group based on whether they received Jinwei Pingchuan decoction， with 30 patients in each group. The treatment group received Jinwei Pingchuan decoction combined with conventional Western medicine therapy， while the control group received conventional Western medicine therapy alone. Both groups received treatment for 7 days. The number of acute exacerbations and lung function indices were followed up and recorded before treatment and three months after treatment. The following outcomes were observed before and after treatment： the number of acute exacerbations， lung function indices （forced expiratory volume in one second ［FEV₁］， percentage of predicted value ［FEV₁%pred］， forced vital capacity ［FVC］， and FEV₁/FVC ratio）， the degree of acute exacerbation， TCM syndrome score， COPD assessment test （CAT） score， modified British Medical Research Council Dyspnea Questionnaire （mMRC） score， C-reactive protein （CRP）， and white blood cell （WBC） count. ResultsAfter 3 months of follow-up， the treatment group showed a significant reduction in the number of acute exacerbations compared with the pre-treatment values （P<0.05）. After treatment， the treatment group had fewer acute exacerbations than the control group （P<0.05）. The degree of acute exacerbation in the treatment group improved significantly compared with the pre-treatment values （P<0.05）. After treatment， the degree of acute exacerbation in the treatment group was improved compared to the control group （P<0.05）. Regarding lung function， FEV₁， FEV₁%pred， FVC， and FEV₁/FVC ratio increased significantly in the treatment group compared with the pre-treatment values （P<0.05）， and similar improvements were observed in the control group （P<0.05）. After treatment， FEV₁ and FVC were higher in the treatment group than the control group （P<0.05）. Regarding TCM syndrome scores， the scores for individual symptoms such as wheezing， cough， expectoration， chest tightness， shortness of breath， and fatigue， as well as the total score， decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）. In the control group， the scores for cough， expectoration， chest tightness， fatigue， and palpitation， as well as the total score， also decreased （P<0.05）. After treatment， the treatment group showed significantly lower scores for wheezing， cough， chest tightness， shortness of breath， and the total score than the control group （P<0.05）. Regarding the CAT score， the scores for cough， expectoration， chest tightness， climbing stairs， going out， activity， and energy， as well as the total score， decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）. In the control group， the scores for cough， expectoration， chest tightness， sleep， energy， and the total score decreased （P<0.05）. After treatment， the treatment group showed significantly lower scores for cough， expectoration， chest tightness， activity， and going out than the control group （P<0.05）. Regarding the mMRC score， CRP level， and WBC count， all these parameters decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）， and similar reductions were observed in the control group （P<0.05）. ConclusionJinwei Pingchuan decoction can reduce the number of acute exacerbations and the degree of acute exacerbation in patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. It also improves lung function and symptoms such as cough and chest tightness， thereby enhancing the quality of life of patients.

Tianxiangdan (TXD), a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion (I/R)-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. High-performance liquid chromatography-mass spectrometry (HPLC-MS) identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha (ERα) protein expression and estradiol (E2) levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group (300 nmol·L^-1 AZD9496 and 15% TXD serum) was compared to a TXD group (15% TXD serum). The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group (1.0 μmol·L^-1 Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERα proteins. A DCFH-DA probe detected reactive oxygen species (ROS) and Fe²⁺, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers (LDH, MDA, and SOD), alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe²⁺ levels, while the AZ group (treated with AZD9496) exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4 (GPX4), with reduced levels of P53 protein and ferritin-heavy polypeptide 1 (FTH1). The AZ group exhibited contrasting effects on these expression levels. The literature indicated a novel connection between ERα and ferroptosis. TXD activates the ERα signaling pathway, promoting protection against I/R-induced myocardial cell ferroptosis. This study provides evidence supporting TXD use for myocardial ischemia treatment, particularly in older female patients who may benefit from its therapeutic outcomes.
Animals ; Ferroptosis/drug effects* ; Estrogen Receptor alpha/genetics* ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Mice ; Humans ; Mice, Inbred C57BL ; Estradiol/metabolism*

Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Objective:To construct univariate and multivariate relapse free survival (RFS) prediction models for breast cancer patients with diabetes mellitus type 2 (T2DM) and to compare and select the model with higher predictive performance.Methods:A total of 912 breast cancer patients treated at the First Affiliated Hospital of Dalian Medical University from January 2010 to December 2016 were included, of which 202 patients had T2DM and 710 patients did not. Kaplan-Meier survival curve was drawn based on whether patients had T2DM, and log-rank test was performed based on whether patients had T2DM. All patients were randomly divided into a training set ( n=640) and a validation set ( n=272) at a ratio of 7∶3. Univariate and multivariate Cox proportional risk regression models were used to analyze RFS in breast cancer patients with the survival package. The "rms" package was employed to construct univariate and multivariate RFS prediction models for breast cancer patients with T2DM. Clinical decision curves and calibration curves were used to validate the models. The receiver operator characteristic (ROC) curve was used to compare and analyze the prediction performance of the two models. Results:There were no statistically significant differences between the training set and the validation set patients in terms of age, T2DM, surgical approach, axillary management methods, T stage, N stage, molecular sub-type, estrogen receptor (ER) 1, ER2, progesterone receptor (PR) , ER and PR consistency, Ki67, human epidermal growth factor receptor 2 (HER2) (all P>0.05) . There was a statistically significant difference in histological grade ( χ2=7.59, P=0.022) . Survival analysis showed that the 5-year RFS rate was 83.7% in patients with T2DM and 92.3% in patients without T2DM ( χ2=16.61, P<0.001) . Univariate analysis revealed that age ( HR=1.04, 95% CI: 1.03-1.06, P<0.001) , T2DM ( HR=2.31, 95% CI: 1.49-3.55, P<0.001) , surgical approach ( HR=2.39, 95% CI: 1.20-4.77, P=0.013) , axillary management methods ( HR=2.62, 95% CI: 1.72-3.98, P<0.001) , T stage (T 2: HR=2.13, 95% CI: 1.36-3.31, P<0.001; T 3: HR=6.90, 95% CI: 3.35-14.22, P<0.001) , N stage (N 2: HR=3.87, 95% CI: 2.12-7.07, P<0.001; N 3: HR=8.61, 95% CI: 4.71-15.75, P<0.001) , molecular sub-type (Luminal B: HR=2.74, 95% CI: 1.17-6.36, P=0.019; HER2 +: HR=3.64, 95% CI: 1.38-9.58, P=0.009; TNBC: HR=4.40, 95% CI: 1.71-11.34, P=0.002) , ER1 (>10%: HR=0.57, 95% CI: 0.37-0.90, P=0.016) , ER2 ( HR=0.57, 95% CI: 0.37-0.89, P=0.015) , and PR ( HR=0.56, 95% CI: 0.37-0.86, P=0.008) were all factors influencing RFS in breast cancer patients. Multivariate analysis demonstrated that age ( HR=1.04, 95% CI: 1.02-1.06, P<0.001) , T2DM ( HR=1.82, 95% CI: 1.16-2.85, P=0.009) , T stage (T 2: HR=1.60, 95% CI: 1.01-2.54, P=0.046; T 3: HR=2.64, 95% CI: 1.22-5.72, P=0.014) , N stage (N 2: HR=3.72, 95% CI: 2.01-6.88, P<0.001; N 3: HR=5.34, 95% CI: 2.78-10.25, P<0.001) , and ER1 (>10%: HR=0.63, 95% CI: 0.39-0.99, P=0.046) were independent factors influencing RFS in breast cancer patients. Based on the 10 and 5 variables with P<0.05 in the univariate and multivariate analyses respectively, the nomograms of the univariate and multivariate prediction models were constructed to evaluate the influence of factors such as T2DM on the postoperative RFS of breast cancer patients. Clinical decision curves and calibration curves indicated that both models had high predictive value for RFS in breast cancer patients, and the predictive results were highly consistent with the actual observed results. ROC curve analysis showed that there was no statistically significant difference in the area under the curve (AUC) of the two models for predicting the RFS rates of breast cancer patients in the training set and validation set at 36, 60, and 84 months (all P>0.05) , indicating that the predictive efficacy of the two models was comparable. The multivariate model is more suitable for clinical application because it uses fewer variables. Conclusions:Breast cancer patients with T2DM have poorer prognosis. Age, T2DM, T stage, N stage, and ER1 are independent factors influencing postoperative RFS in breast cancer patients. The multi-factor prediction model of RFS in breast cancer patients based on T2DM is more suitable for clinical application due to its higher predictive efficacy and fewer variables.

Objective To discuss the effect of different particle activities and tumor shrinkage speed on the dosimetric parameters of the target area at the same prescription dose after 125I particle implantation.Methods A 6cm-sized cube tumor model was outlined by using a computerized three-dimensional treatment planning system(3D-TPS)with a prescription dose(PD)of 100 Gy,and 125I particle activities of 0.4 mCi and 0.8 mCi were selected.Assuming that the tumor shrinks centripetally after seed implantation and that the 125I particles were uniformly and centripetally concentrated without shedding or wandering,the tumor volume shrank at different rates every month after implantation(0,5％,10％,15％,20％,25％,30％,35％,40％,45％and 50％),according to the different activities of 125I particles,the experiments were divided into A1-K1 group(0.4 mCi)and A2-K2 group(0.8 mCi).Based on the 125I particle decay law,the validation program(using TPS simulation of the A1-K1 group and A2-K2 group at postoperative 1,2,3,4,5 and 6 months)obtained the dose received by 90％of the target volume(D90)in the two groups with different 125I particle activities at different postoperative time points,the percentages of the target volume covered by the 100％,150％and 90％prescription dose(V100,V150,V90),and the mean dose(Dmean).By comparing the differences in D90,V100,V150,V90 and Dmean after tumor implantation of 125I particles with different activities,the dosimetric impact of the tumor target area shrinking at a rate of 0～50％after implantation of 125I particles with different activities into tumor tissues was analyzed.Results When the monthly shrinkage rate of the tumor target area was≤30％,there was no obvious difference in D90 between the 0.4 mCi group and 0.8 mCi group in 1～6 months after surgery.When the monthly shrinkage rate of the tumor target area was＞30％,the D90 of 0.8 mCi group was higher than that of 0.4 mCi group;when the monthly shrinkage rate of the tumor target area was＜25％,the V90 of 0.4 mCi group was higher than that of 0.8 mCi group,and the changes of V90 of the two groups tended to be the same in the 5th～6th month after surgery.When the monthly shrinkage rate of the tumor target area was ≥30％,the V90 of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more significant,the results of V100 were consistent with those of V90.When the monthly shrinkage rate of tumor target area＜35％,V150 of 0.4 mCi group was higher than that of 0.8 mCi group,when the monthly shrinkage rate of tumor target area ≥35％,V150 of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more prominent.When the monthly shrinkage rate of tumor target area＜25％,Dmean of 0.4 mCi group was higher than that of 0.8 mCi group,when the monthly shrinkage rate of tumor target area ≥25％,Dmean of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more obvious.Conclusion With the same prescription dose,when the tumor target area shrinks at a rate of＜30％per month,the activity of 125I particles has little effect on D90,and all V90,V100,V150 and Dmean in the low activity group are higher than those in the high activity group,meanwhile the homogeneity of the target area is relatively good;when the monthly shrinkage rate of tumor target area ≥35％,all D90,V90,V100,V150 and Dmean in the high activity group are higher than those in the low activity group,and the duration of the presence of high-dose area is long.This difference becomes more obvious with the increasing of the monthly shrinkage rate of the target area.