Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

Objective: To explore the therapeutic mechanism of puerarin in treating rheumatoid arthritis (RA) rats based on the serine/tyrosine protein kinase B (AKT)-phosphorylated forkhead box protein O1 (FOXO1)-interleukin-9 (AKT-FOXO1-IL-9) signaling pathway. Methods : 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . Results: Compared with the blank group , the model group had the lowest toe thickness , and X-ray images showed more obvious segmental stenosis and more severe marginal bone invasion ; scaly like changes appeared at the edges of joints stained with safranin green , accompanied by the exudation of inflammatory cells and increased proliferation and secretion of chondrocytes ; the expression levels of inflammatory factors IL-9 and rheumatoid factors were the highest , and the expression levels of AKT and FOXO1 proteins were the highest (P < 0. 05) . Compared with the model group , the toe thickness of rats treated with different doses of puerarin decreased ; X-ray images showed that the puerarin treatment group of rats showed improvement in plantar joint stenosis and marginal bone invasion ; the results of safranin green staining showed that after treatment with different doses of puerarin , the infiltration of inflammatory cells decreased , and the expression levels of inflammatory factor IL-9 , rheumatoid factors , AKT , and FOXO1 proteins decreased significantly ( P < 0. 05 ) , with the high-dose puerarin group showing the most significant difference. Compared with the high-dose puerarin group , the positive control group showed a significant decrease in the above results and statistical differences (P < 0. 05) . Conclusion Puerarin has a good therapeutic effect on rats with RA by inhibiting the AKT-FOXO1-IL-9 pathway. The high-dose puerarin group (60 mg/kg) has the best therapeutic effect and the results show a dose-response relationship.

OBJECTIVE: To explore the genetic characteristics and pathogenesis for a child with mosaicism trisomy 21 and Congenital leukemia (CL). METHODS: A child who was admitted to Ningbo Women and Children's Hospital in March 2023 was selected as the study subject. A retrospective analysis was carried out on the clinical data, laboratory test results, immunophenotyping, and genetic characteristics of the child. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2024-063). RESULTS: Whole genome sequencing (WGS) revealed that the child has mosaicism trisomy of chromosome 21, with a ratio of approximately 74%. In addition, copy number variations involving multiple OMIM genes that could explain his clinical phenotype were detected and rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). No pathogenic variant was detected with the GATA1 gene. Blood immune typing of the child conformed to the immunophenotype of acute myeloid leukemia. CONCLUSION For children with trisomy 21, even in the absence of GATA1 gene variants, the occurrence of CL should be monitored, and early diagnosis and treatment are of great significance for improving the prognosis.
Child, Preschool ; Humans ; DNA Copy Number Variations/genetics* ; Down Syndrome/genetics* ; GATA1 Transcription Factor/genetics* ; Leukemia/congenital* ; Mosaicism ; Mutation ; Retrospective Studies ; Whole Genome Sequencing

Objective To detect the expression of translationally-controlled tumor protein 1(TPT1)in renal cell carcinoma(RCC)and to explore its role in RCC.Methods Microarray dataset GSE15641(including 23 normal kidney tissue samples and 32 RCC tissue samples)was downloaded from the Gene Expression Omnibus,and differentially expressed genes between RCC tissue and normal kidney tissue were screened using R 4.3.0 software.The TPT1 expression in RCC tissue and adjacent non-tumor tissue of 90 patients diagnosed and treated at Affiliated Hospital of Nantong University,as well as in human RCC cells(769-P,786-O,ACHN,and Caki-1)and human embryonic kidney 293 cell(HEK293)was detected by quantitative polymerase chain reaction(qPCR)and Western blotting.The relationship between TPT1 expression and clinical pathological characteristics of RCC patients was analyzed by χ2 test.The clinical data of 522 RCC patients were derived from The Cancer Genome Atlas,and the correlation between TPT1 expression and prognosis of RCC patients was analyzed by receiver operating characteristic(ROC)curve and Kaplan-Meier survival curve.After in vitro transfection of TPT1 small interfering RNA(siRNA)and its negative control(NC)into 786-O and Caki-1 cells,the TPT1 expression was detected by qPCR and Western blotting;the proliferation,migration,and invasion were detected by cell counting kit 8 assay,scratch assay,and Transwell assay,respectively;and the expression of apoptosis-related proteins was detected by Western blotting.Results TPT1 expression was significantly upregulated in the RCC tissue and cells compared with the normal kidney tissue and HEK293 cells(all P＜0.05).The RCC patients with low TPT1 expression levels had significantly smaller tumor size and lower metastasis rate than those with high TPT1 expression levels(both P＜0.05).The ROC curve analysis results indicated that TPT1 had high diagnostic value for RCC(area under curve was 0.856 9,95%confidence interval was 0.804 5-0.909 3,P＜0.001).The Kaplan-Meier survival analysis results showed that the overall survival of RCC patients in the low TPT1 expression group was significantly longer than that in the high TPT1 expression group(P=0.018 4).In the cell experiment,compared with the siRNA NC group,the proliferation activity,scratch healing rate,and invading transmembrane cell number of 786-O and Caki-1 cells were significantly decreased after transfection with TPT1 siRNA(all P＜0.01);the expression levels of B-lymphoma gene 2(Bcl-2)and matrix metalloproteinase-9 were significantly decreased,while the expression of Bcl-2 associated X protein was significantly increased(all P＜0.05).Conclusion TPT1 is involved in the progression of RCC and may be a potential therapeutic target for RCC.

Objective:To explore the clinical effects of combined surgical and high-frequency electro-acupuncture treatment for aesthetic restoration in children with eyelid split nevus.Methods:A retrospective analysis was conducted on the medical records of children treated for eyelid split nevus in the Plastic Surgery Department of the First Affiliated Hospital of Army Medical University from January 2019 to December 2023. All cases underwent combined surgical excision and high-frequency electro-acupuncture vaporization. Surgical removal was used for nevi with significant pigmentation and deep involvement, and high-frequency electro-acupuncture was simultaneously applied to vaporize residual superficial pigmentation layer by layer based on the depth of the pigmentation. The wounds were repaired using either direct suturing or local flap transfer. Postoperative management included the application of growth factors and anti-scar treatments. Postoperative healing, adverse effects, and pigment clearance rate (categorized as healed, significant effect, improved, or ineffective) were observed by comparsons of the pre-treatment and the last follow-up photographs. Eyelid function, appearance, and scar hypertrophy were assessed during follow-up, and family satisfaction (categorized as very satisfied, satisfied, or dissatisfied) was surveyed via telephone.Results:Five children were included, with one male and four females aged between 2 and 10 years (average 7 years). Pigment areas ranged from 0.3 cm × 0.5 cm to 1.7 cm × 1.1 cm, with surgical excision areas from 0.3 cm × 0.4 cm to 1.5 cm × 1.1 cm. All children had good wound healing without complications such as infection, flap ischemic necrosis, wound dehiscence or bleeding. The pigment clearance rate was over 90%, achieving a healed effect. During the follow-up of 14 to 48 months (average 24.2 months), all patients had normal eyelid function without difficulties in opening or closing the eyes, or epiphora. The eyelid appearance was satisfactory without asymmetry, ptosis, ectropion or hypertrophic scars. The aesthetic outcomes and functionality of the eyelids were ideal, and satisfaction was generally rated as very satisfied.Conclusion:Surgical removal combined with high-frequency electro-acupuncture is beneficial for preserving aesthetic appearance while pigmentation in children with eyelid split nevus is removed, offering a new treatment option.

Purpose To explore the value of CT-based radiomics in the preoperative prediction of lymphatic invasion of node-negative gastric cancer,and to construct a nomogram combined with clinical variables.Materials and Methods The clinical and CT imaging data of 173 gastric cancer patients with lymph node negative and pathologically confirmed gastric cancer in the Sir Run Run Shaw Hospital from January 2019 to June 2021 were retrospectively analyzed.A total of 60 cases with lymphovascular invasion(LVI)positive patients and 113 cases with LVI negative patients were included,and randomly divided into train cohort(n=121)and test cohort(n=52)at 7∶3.Based on the train cohort,the clinical model,the radiomics model,the fusion model were constructed and verified in the test cohort.Clinical data and conventional CT features included age,gender,tumor marker,tumor location,tumor morphology,enhancement range,etc.The clinical significant variables were selected through univariate and multivariate analysis to establish the clinical model.The tumor regions of interest were segmented and radiomics features were extracted by using the 3D-Slicer software.Key features were screened through least absolute shrinkage and selection operator regression analysis,and then the radiomics model was constructed with random forest algorithm,and converted to random forest score(RF score).The fusion model was constructed via combining clinical significant variables and RF score,and visualized as a nomogram.The receiver operator characteristic curve and area under curve(AUC)were used to evaluate the prediction performance of the models.Decision curve analysis was used to calculate the clinical practicability.Results The radiomics model was superior to the clinical model.The radiomics model AUC of the train cohort and the test cohort were 0.872(0.810 to 0.935)and 0.827(0.707 to 0.947),the clinical model AUC were 0.767(0.682 to 0.852)and 0.761(0.610 to 0.913).The nomogram further improved the predictive efficiency,the AUC in train cohort and test cohort reached 0.898(0.842 to 0.953)and 0.844(0.717 to 0.971),respectively.Decision curve analysis demonstrated clinical benefits of nomogram.Conclusion The radiomics model can be used to preoperatively predict LVI of node-negative gastric cancer.The nomogram can further improve the prediction efficiency.

Objective:To explore the clinical effects of combined surgical and high-frequency electro-acupuncture treatment for aesthetic restoration in children with eyelid split nevus.Methods:A retrospective analysis was conducted on the medical records of children treated for eyelid split nevus in the Plastic Surgery Department of the First Affiliated Hospital of Army Medical University from January 2019 to December 2023. All cases underwent combined surgical excision and high-frequency electro-acupuncture vaporization. Surgical removal was used for nevi with significant pigmentation and deep involvement, and high-frequency electro-acupuncture was simultaneously applied to vaporize residual superficial pigmentation layer by layer based on the depth of the pigmentation. The wounds were repaired using either direct suturing or local flap transfer. Postoperative management included the application of growth factors and anti-scar treatments. Postoperative healing, adverse effects, and pigment clearance rate (categorized as healed, significant effect, improved, or ineffective) were observed by comparsons of the pre-treatment and the last follow-up photographs. Eyelid function, appearance, and scar hypertrophy were assessed during follow-up, and family satisfaction (categorized as very satisfied, satisfied, or dissatisfied) was surveyed via telephone.Results:Five children were included, with one male and four females aged between 2 and 10 years (average 7 years). Pigment areas ranged from 0.3 cm × 0.5 cm to 1.7 cm × 1.1 cm, with surgical excision areas from 0.3 cm × 0.4 cm to 1.5 cm × 1.1 cm. All children had good wound healing without complications such as infection, flap ischemic necrosis, wound dehiscence or bleeding. The pigment clearance rate was over 90%, achieving a healed effect. During the follow-up of 14 to 48 months (average 24.2 months), all patients had normal eyelid function without difficulties in opening or closing the eyes, or epiphora. The eyelid appearance was satisfactory without asymmetry, ptosis, ectropion or hypertrophic scars. The aesthetic outcomes and functionality of the eyelids were ideal, and satisfaction was generally rated as very satisfied.Conclusion:Surgical removal combined with high-frequency electro-acupuncture is beneficial for preserving aesthetic appearance while pigmentation in children with eyelid split nevus is removed, offering a new treatment option.

Objective:To provide evidence-based recommendations for the prevention and management of lower limb ischemia in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients during treatment according to search, evaluate, and summarize the best evidence on the prevention and management of lower limb ischemia in patients with VA-ECMO.Methods:Based on the PIPOST framework (population, intervention, professional, outcome, setting, and type of evidence), an evidence-based question was formulated. A systematic search was conducted according to the "6S" evidence pyramid model in both domestic and international databases, as well as professional association websites, for all evidence related to the prevention and management of lower limb ischemia in VA-ECMO patients (aged ≥18 years). The types of evidence included clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and original studies. The search was conducted from the construction of the databases to February 2024. Two researchers independently conducted a literature quality evaluation, extracted and summarized evidence from the studies that met the quality criteria.Results:A total of 13 articles were included, consisting of 3 clinical decisions, 3 guidelines, 3 expert consensus, 3 systematic reviews, and 1 randomized controlled trial. A total of 18 pieces of evidence in 7 dimensions were summarized, including risk factors of VA-ECMO lower limb ischemia, evaluation before catheterization, evaluation and monitoring during treatment, prevention of lower limb ischemia, treatment of lower limb ischemia, management of distal perfusion catheter (DPC), and monitoring after VA-ECMO weaning.Conclusion:This evidence summary provides evidence-based recommendations for the prevention and management of lower limb ischemia in VA-ECMO patients, aiming to assist clinical healthcare professionals in developing tailored strategies for the prevention and management of lower limb ischemia based on during VA-ECMO support.

Objective:To investigate the clinical efficacy of pentoxifylline sequential therapy combined with rasagiline and levodopa in the treatment of elderly patients with symptoms of Parkinson disease (PD), and the influence on hemorheology and serum Toll-like receptor 4 (TLR4) signaling pathway downstream related inflammatory factors.Methods:A prospective study method was used to select 90 elderly patients with PD with fluctuating symptoms who were admitted to the Eighth People′s Hospital of Hebei Province from June 2021 to October 2022 as research objects. The patients were divided into observation group and control group with 45 cases in each group according to random number table method. The observation group was treated with pentoxifylline sequential therapy combined with rasagiline and levodopa. The control group was treated with rasagiline combined with levodopa. The clinical efficacy of the two groups was compared. The unified Parkinson disease rating scale (UPDRS), Montreal cognitive assessment scale (MoCA), Berg balance scale (BBS) and 39-item Parkinson disease quality of life questionnaire (PDQ-39) were scored before and after treatment. Hemorheology indexes and serum levels of related inflammatory factors downstream of TLR4 signaling pathway, including whole blood high viscosity (HBV), whole blood low shear viscosity (LBV), plasma viscosity (PV), fibrinogen (FIB); TLR4, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF) -α, were detected before and after treatment in both groups. The adverse reactions of the two groups were compared.Results:The total effective rate in observation group was significantly higher than that in control group: 93.33% (42/45) vs. 77.78% (35/45), and there was statistical difference ( P<0.05). After treatment, the UPDRS mental activity and emotional disorders, daily living ability, motor function, motor complications scores and PDQ-39 score of the two groups were significantly lower than before treatment, the MoCA and BBS scores were significantly higher than before treatment, and the improvement was more significant in the observation group, there were statistical differences ( P<0.05). After treatment, HBV, LBV, PV and FIB in the observation group were significantly decreased compared with those before treatment: (6.52 ± 0.92) mPa·s vs. (7.25 ± 1.24) mPa·s, (11.45 ± 1.24) mPa·s vs. (14.13 ± 1.64) mPa·s, (1.55 ± 0.17) mPa·s vs. (1.88 ± 0.22) mPa·s, (3.25 ± 0.47) g/L vs. (3.82 ± 0.52) g/L, and there were statistical differences ( P<0.05). There were no significant differences in hemorheology indexes of control group before and after treatment ( P>0.05). After treatment, serum levels of TLR4, IL-1β, IL-6 and TNF-α in both groups were significantly decreased compared with those before treatment, and the indexes in observation group were significantly lower than those in control group: (2.07 ± 0.18) ng/L vs. (2.58 ± 0.21) ng/L, (1.42 ± 0.17) ng/L vs. (2.28 ± 0.25) ng/L, (1.56 ± 0.22) ng/L vs. (2.42 ± 0.28) ng/L, (46.31 ± 3.17) ng/L vs. (54.34 ± 3.65) ng/L, and the differences were statistically significant ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Pentoxifylline sequential therapy combined with rasagiline and levodopa can effectively improve the hemorheology of elderly patients with PD accompanied by symptom fluctuations, reduce the levels of related inflammatory factors downstream of serum TLR4 signaling pathway, and improve clinical efficacy.

Objective To investigate the content stability of polymyxin B sulfate in high concentration solution and its finished infusion,and to provide a scientific basis for clinical administration.Methods Polymyxin B sulfate was dissolved in 0.9%sodium chloride injection and 5%glucose solution to the concentrations of 0.5 mg·mL-1,1 mg·mL-1 and 5 mg·mL-1,respectively.The content of polymyxin B was determined at 0,2,4,6,8,12,16,20 and 24 h by high-performance liquid chromatography under storage conditions of 4℃and 25℃.Results Polymyxin B sulfate was stable in the concentrations of 0.5 mg·mL-1,1 mg·mL-1 and 5 mg·mL-1,respectively,in 0.9%sodium chloride injection or 5%glucose injection.Under the storage conditions of 4℃and 25℃,the content of polymyxin B1 and polymyxin B2 ranged from 97.23%to 101.26%and 97.30%to 102.63%,respectively.Conclusion Polymyxin B sulfate was stable within 24 h dissolved either in 0.9%sodium chloride injection or in 5%glucose injection with the concentrations of 0.5 mg·mL-1,1 mg·mL-1 and 5 mg·mL-1 under the storage condition of 4℃and 25℃.