ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

ObjectiveTo investigate the inhibitory effect of Biejiajian Pills （BJJW） on the growth of liver cancer， as well as its potential mechanism in mediating the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway through mitochondrial energy metabolism. MethodsHuman hepatoma Huh7 cells were used to establish a nude mouse model of subcutaneous xenograft tumor. A total of 18 tumor-bearing nude mice were randomly divided into model group， BJJW group （2.2 g/kg）， and metformin group （250 mg/kg）， and the corresponding drug was given by gavage for 14 consecutive days. Tumor volume and weight were monitored during the experiment； HE staining was used to observe histopathological changes； the levels of reactive oxygen species （ROS） and adenosine triphosphate （ATP） in tumor tissue were measured； immunohistochemistry and Western blotting were used to measure the expression levels of proteins associated with the AMPK/mTOR pathway. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Tukey’s test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the model group， the BJJW group had a tumor inhibition rate of 45.73%， with significant reductions in both tumor volume and weight （P<0.01）. Pathological examination showed that compared with the model group， the BJJW group had a significant reduction in the number of tumor cells and the presence of extensive necrosis. Mechanistic studies showed that compared with the model group， the BJJW group had a significant increase in ROS level （P<0.001） and a significant reduction in ATP level （P<0.001）， as well as significant increases in p-AMPK/AMPK ratio （0.81±0.20 vs 0.13±0.04， P<0.01） and p-ULK1/ULK1 ratio （0.69±0.17 vs 0.18±0.13， P<0.01） and a significant reduction in p-mTOR/mTOR ratio （1.34±0.16 vs 3.20±0.62， P<0.01）. ConclusionBJJW may inhibit the growth of liver cancer by inducing mitochondrial energy metabolism dysfunction， increasing the level of ROS， reducing the level of ATP， and activating the AMPK/mTOR signaling pathway.

Objective To explore the value of multimodal MRI combined with digital breast 3D tomography(DBT)in evaluating lymphatic vascular infiltration(LVI)in patients with invasive breast cancer-non special type(IBC-NST)mass type.Methods A total of 102 patients with IBC-NST mass type were divided into LVI group and non LVI group based on whether LVI occurred.The influencing factors of LVI were analyzed by using multivariate logistic regression.Clinical value of multimodal MRI combined with DBT in evaluating LVI in patients with IBC-NST mass type were analyzed by receiver operating characteristic(ROC)curve.Results Multivariate logistic analysis showed that apparent diffusion coefficient(ADC)value,maximum tumor diameter and peritumoral edema were independent risk factors for LVI in IBC-NST mass type(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of ADC value,maximum tumor diameter and peritumoral edema alone and in combination for LVI in patients with IBC-NST mass type were 0.749,0.655,0.638 and 0.791,respectively.Conclusion ADC value and its combined application model have high efficacy in evaluating LVI in patients with IBC-NST mass type.

Objective:To investigate the influence of contrast-enhanced computed tomography(CECT)on dose calculation in magnetic resonance imaging(MRI)-guided online adaptive radiotherapy(oART)based on the electron density(ED)assignment method for rectal cancer.Methods:A retrospective analysis was conducted on the medical data of 15 patients with locally advanced rectal cancer at middle-low segments,who admitted to the Chinese PLA General Hospital between December 2023 and April 2025.All patients underwent both plain computed tomography(PCT)and CECT scans during location.The average HU and ED value of all organs that were extracted from PCT and CECT images in the treatment plan system were obtained,and the influences of contrast agent of intake on image characteristics of the structure of each organ(small intestine,femoral head,bladder)were analyzed.PCT was used as referred image to design reference plan(Pref).The synthetic CT(sCT)was simulated and generated on the basis of PCT and CECT,respectively.The beam flow field that was same with Pref was used to recalculate dose on sCT,and then,the online plan(PPCT)based on PCT,and the online plan(PCECT)based on CECT were obtained,respectively,which can simulate the online dose calculation of MRI-guided online adaptive radiotherapy(oART).The Pref was used as reference to compare dosimetric parameters for target region and organ at risk(OAR)through dose volume histogram(DVH)and planed evaluation indicators.Additionally,three dimension(3D)slicer software was used to perform γ analysis for the results of dose distribution,and explore the differences among PPCT,PCECT and Pref on dose distribution.Results:In terms of image characteristics,the HU values of soft-tissue organs(intestine,bladder,spinal cord,soft tissue)and planning target volume(PTV)in CECT were higher than those in PCT,and the differences of them were statistically significant(Zintestines=-2.188,Zbladder=-3.196,tspinal cord=-3.767,tsoft tissue=-10.083,tPTV=-4.693,P<0.05),while its influence was less on bone tissue.The statistical results of ED were consistent with those of HU.Regarding to dosimetric parameters,there was no statistically significant difference in target coverage rate between PPCT and Pref(P>0.05),and the D50%of the PPCT[(2724.25±19.91)cGy]was higher than that of the Pref[(2718.99±21.13)cGy],and the difference was statistically significant(t=-3.679,P=0.002).However,the target coverage rate of PCECT was 94.65(94.04,95.27)%,and the difference of that between PCECT and Pref was statistically significant(Z=-2.158,P=0.031).For OAR,the differences of Dmax value of the small intestine,and the V20 of the left femoral head between PPCT and Pref were significant(Z=-2.556,-2.529,P<0.05).The differences of the Dmax of small intestine,and the D50%of bladder between PCECT and Pref were significant(t=-4.821,2.171,P<0.05).The comparative γ passed rates of PPCT,PCECT and Pref under the standards of 3 mm/3%and 2 mm/2%were all above 95%,and the differences were not significant(P>0.05).Conclusions:The influence of CECT on dose calculation in MRI-guided oART based on ED assignment method for rectal cancer is relatively small,which can be directly used in the design of reference plan,but the maximum dose of radiation-sensitive organs such as the small intestine should be paid attention.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

OBJECTIVE: To summarize the research and clinical application progress of foot lengthening surgery. METHODS: Relevant research literature on foot lengthening surgery in recent years at home and abroad was reviewed, and a summary was made from aspects such as the types of lengthening surgery, the types of foot diseases treated by clinical application, effectiveness, and complications. RESULTS: Bone defects and shortening deformities of the foot are relatively common clinically. As an innovative treatment method, foot lengthening surgery has gradually attracted attention, mainly including the Ilizarov technique and one-stage bone grafting lengthening surgery. The former promotes bone regeneration based on the tension-stress principle and is widely used in the treatment of calcaneal defects and congenital metatarsal brachymetatarsia, achieving good curative effects. However, there are also complications such as pin-tract infection, joint stiffness and contracture, non-union and delayed union of bone, re-fracture, and alignment deviation. The latter has a short treatment cycle, but the lengthening length is limited. Bone graft resorption and soft tissue complications are its main complications. CONCLUSION Foot lengthening surgery will develop towards the direction of personalization, intelligence, and precision. With the help of multi-center research, biological materials, and intelligent technologies, the effectiveness and safety will be further improved to better restore the function and appearance of the foot.
Humans ; Bone Transplantation/methods* ; Bone Lengthening/methods* ; Ilizarov Technique ; Osteogenesis, Distraction/methods* ; Foot Deformities/surgery* ; Postoperative Complications ; Treatment Outcome ; Foot/surgery*

Objective:To investigate the influence of contrast-enhanced computed tomography(CECT)on dose calculation in magnetic resonance imaging(MRI)-guided online adaptive radiotherapy(oART)based on the electron density(ED)assignment method for rectal cancer.Methods:A retrospective analysis was conducted on the medical data of 15 patients with locally advanced rectal cancer at middle-low segments,who admitted to the Chinese PLA General Hospital between December 2023 and April 2025.All patients underwent both plain computed tomography(PCT)and CECT scans during location.The average HU and ED value of all organs that were extracted from PCT and CECT images in the treatment plan system were obtained,and the influences of contrast agent of intake on image characteristics of the structure of each organ(small intestine,femoral head,bladder)were analyzed.PCT was used as referred image to design reference plan(Pref).The synthetic CT(sCT)was simulated and generated on the basis of PCT and CECT,respectively.The beam flow field that was same with Pref was used to recalculate dose on sCT,and then,the online plan(PPCT)based on PCT,and the online plan(PCECT)based on CECT were obtained,respectively,which can simulate the online dose calculation of MRI-guided online adaptive radiotherapy(oART).The Pref was used as reference to compare dosimetric parameters for target region and organ at risk(OAR)through dose volume histogram(DVH)and planed evaluation indicators.Additionally,three dimension(3D)slicer software was used to perform γ analysis for the results of dose distribution,and explore the differences among PPCT,PCECT and Pref on dose distribution.Results:In terms of image characteristics,the HU values of soft-tissue organs(intestine,bladder,spinal cord,soft tissue)and planning target volume(PTV)in CECT were higher than those in PCT,and the differences of them were statistically significant(Zintestines=-2.188,Zbladder=-3.196,tspinal cord=-3.767,tsoft tissue=-10.083,tPTV=-4.693,P<0.05),while its influence was less on bone tissue.The statistical results of ED were consistent with those of HU.Regarding to dosimetric parameters,there was no statistically significant difference in target coverage rate between PPCT and Pref(P>0.05),and the D50%of the PPCT[(2724.25±19.91)cGy]was higher than that of the Pref[(2718.99±21.13)cGy],and the difference was statistically significant(t=-3.679,P=0.002).However,the target coverage rate of PCECT was 94.65(94.04,95.27)%,and the difference of that between PCECT and Pref was statistically significant(Z=-2.158,P=0.031).For OAR,the differences of Dmax value of the small intestine,and the V20 of the left femoral head between PPCT and Pref were significant(Z=-2.556,-2.529,P<0.05).The differences of the Dmax of small intestine,and the D50%of bladder between PCECT and Pref were significant(t=-4.821,2.171,P<0.05).The comparative γ passed rates of PPCT,PCECT and Pref under the standards of 3 mm/3%and 2 mm/2%were all above 95%,and the differences were not significant(P>0.05).Conclusions:The influence of CECT on dose calculation in MRI-guided oART based on ED assignment method for rectal cancer is relatively small,which can be directly used in the design of reference plan,but the maximum dose of radiation-sensitive organs such as the small intestine should be paid attention.

Objective To explore the value of multimodal MRI combined with digital breast 3D tomography(DBT)in evaluating lymphatic vascular infiltration(LVI)in patients with invasive breast cancer-non special type(IBC-NST)mass type.Methods A total of 102 patients with IBC-NST mass type were divided into LVI group and non LVI group based on whether LVI occurred.The influencing factors of LVI were analyzed by using multivariate logistic regression.Clinical value of multimodal MRI combined with DBT in evaluating LVI in patients with IBC-NST mass type were analyzed by receiver operating characteristic(ROC)curve.Results Multivariate logistic analysis showed that apparent diffusion coefficient(ADC)value,maximum tumor diameter and peritumoral edema were independent risk factors for LVI in IBC-NST mass type(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of ADC value,maximum tumor diameter and peritumoral edema alone and in combination for LVI in patients with IBC-NST mass type were 0.749,0.655,0.638 and 0.791,respectively.Conclusion ADC value and its combined application model have high efficacy in evaluating LVI in patients with IBC-NST mass type.