Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

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 By observing the regulatory effect of Strengthening Spleen and Eliminating Cancer Formula on N6-methyladenosine(m6A)methyltransferase,To explore the effect of Strengthening Spleen and Eliminating Cancer Formula on inhibiting the IRX5 m6A level in colorectal cancer(CRC),the regulatory effect on N6-methyladenosine(m6A)methyltransferase was observed.Methods Clinically,m6A hypermethylated genes in colorectal cancer was analyzed by m6A sequencing of pathological tissues from five CRC patients after radical surgery,looking for protein detection indexes for validation.23 BALB/c nude mice were selected and injected with HCT116 cells to establish a nude-mouse transplantation model of human colorectal cancer.They were divided into Model group,Western medicine group(5-fluorouracil group),Chinese medicine group(Jianpi Xiaoai Formula low-dose group,Jianpi Xiaoai Formula high-dose group),with 6 rats in each group,5 rats in control group.The tumor volume of all groups was compared.The overall methylation level of m6A was detected by colorimetric method.The protein expression levels of METTL3,METTL14,and WTAP,in tumor were detected by Western blot.The SRAMP website was used to predict the m6A sites of IRX5.HCT116 cells were treated with oe-NC,oe-METTL3,sh-NC,and sh-METTL3.The expression of IRX5 protein was detected by Western blot.HCT116 cell line was treated with Jianpi Xiaoai Formula drug-containing serum,and transfected with oe-METTL3 and oe-IRX5.The group was set as followed:control group,Jianpi Xiaoai Formula drug-containing serum group,Jianpi Xiaoai Formula drug-containing serum group+oe-NC,Jianpi Xiaoai Formula drug-containing serum group+oe-METTL3,Jianpi Xiaoai Formula drug-containing serum group+oe-IRX5,cell cloning experiment and Transwell experiment were performed to detect cell proliferation,migration and invasion ability of each group.The protein expression levels of METTL3 and IRX5 were detected by Western blot.Results The results of m6A sequencing of genes showed that the m6A methylation level increased in patients with CRC,and the m6A methylation levels of SOX1 and IRX5 were significantly elevated.Compared with the model group,the tumor volume of Jianpi Xiaoyou Formula high-dose group,low-dose group and 5-Fu group decreased significantly(P<0.01),and the tumor inhibition effect was more obvious with the increase of Jianpi Xiaoai Formula concentration(P<0.01).The methylation level of m6A in Jianpi Xiaoai Formula high dose group,low dose group and 5-Fu group decreased significantly(P<0.01).The SRAMP website predicted that IRX5 contained multiple m6A sites.Overexpression of METTL3 promoted the expression of IRX5 protein(P<0.001),while knockdown of METTL3 inhibited the expression of IRX5 protein(P<0.001).The drug-containing serum of Jianpi Xiaoai Formula could inhibit the protein expression of METTL3 and IRX5(P<0.05)and inhibit the proliferation,migration and invasion of HCT116(P<0.01).Overexpression of METTL3 and IRX5 reversed the inhibitory effect of Jianpi Xiaoai Formula on HCT116 evil phenotype(P<0.01).Conclusion Jianpi Xiaoai Formula may inhibit METTL3 expression mediated IRX5 low expression to inhibit the progression of colorectal cancer.

Objective To explore the application effect of dexmedetomidine combined with ropivacaine for quadratus lumborum block at the lateral supra-arcuate ligament(QLB-LSAL) in open hepatocellular carcinoma resection.Methods A prospective study was conducted in 60 patients who underwent elective open hepatocellular carcinoma resection at Jining First People's Hospital. The patients were randomly divided into the compound group and the control group,with 30 cases in each group. Patients in the compound group received QLB-LSAL combined general anesthesia,and patients in the control group received simple general anesthesia. All patients underwent patient controlled intravenous analgesia (PCIA)postoperatively. The mean arterial pressure (MAP),heart rate (HR) and visual analogue scale (VAS) scores during rest and coughing at different time points were observed and compared between the two groups. The number of postoperative PCIA compressions,the dosage of sufentanil,the first postoperative exhaust time,the first postoperative ambulation time,the hospital stay and the occurrence of adverse reactions of the two groups were recorded. Results In the compound group,the HR and MAP were significantly lower than those of the control group at the time of skin incision (T2) and at the end of surgery (T3);the VAS scores during rest and coughing were significantly lower than those of the control group at the time of exiting the anesthesia recovery room and 6 hours and 12 hours after surgery;and the PCIA compression times were significantly less than those of the control group;the dosage of sufentanil was significantly lower than that in the control group 0 to 24 hours after surgery,and the dosage of sufentanil was higher than that in the control group 25 to 48 hours after surgery;the first postoperative ambulation time and the first postoperative exhaust time were significantly earlier than those in the control group;and the above differences were statistically significant(P<0.05). There was no significant difference in the HR or MAP at 5 minutes into the operating room (T0) and 5 minutes before skin incision (T1),VAS scores during rest and coughing 24 hours and 48 hours after surgery,hospital stay and incidence of adverse reactions between the two groups (P>0.05).Conclusion For patients with open hepatocellular carcinoma resection,dexmedetomidine combined with ropivazine for QLB-LSAL can provide more ideal postoperative analgesia,reduce perioperative opioid consumption,and have less impact on circulatory system,which is conducive to rapid postoperative recovery.

OBJECTIVE To investigate the pharmacodynamics and related mechanisms of Anmei Dan on hippocampus of mice with coronary heart disease complicated with depression.METHODS The coronary heart disease model combined with chronic and unpredictable mild stress depression model was established,and the mice were randomly divided into blank group,model group,low dose group(1.5 g·kg-1),high dose group(3 g·kg-1)and atorvastatin group(0.3 g·kg-1).Sucrose preference test,open field test and forced swimming test were used to evaluate the behavioral changes of mice.qPCR and ELISA were employed to ascertain the mR-NA expression of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumour necrosis factor-α(TNF-α)in the hippocampus.The changes of neurons and Nissl bodies in CA1,CA3 and DG regions of hippocampus were observed by Nissl staining.The expression of key proteins was detected by Western blot.RESULTS Compared with the blank group,the sucrose preference rate of mice in the model group was decreased(P<0.01),the forced swimming immobility time was extended(P<0.01)and the movement distance in the open field experiment was not significantly changed.The levels of total cholesterol(TC),triglyceride(TG)and low density lipopro-tein cholesterol(LDL-C)were increased significantly(P<0.01)and the level of high density lipoprotein cholesterol(HDL-C)was decreased significantly(P<0.01).The mRNA level and content of IL-1β,IL-6 and TNF-α were significantly increased(P<0.01).The expression of glutamate receptor 1(GluR1),postsynaptic densitin-95(PSD-95),brain-derived neurotrophic factor(BDNF)and phosphorylated calmodulin-dependent kinase(p-CaMKⅡ)in hippocampus was decreased(P<0.01).The expression of cytoskeletal activity regulatory protein(Arc)was increased(P<0.01).In the model group,the cell structure was irregular and differ-ent degrees of damage occurred,the Nissl bodies decreased or disappeared,and the cell membrane broke.Compared with the model group,the sucrose preference rate of mice in each administration group was significantly increased(P<0.01),the immobility time in forced swimming experiment was significantly decreased(P<0.01),and the levels of TC,TG and LDL-C of mice in Anmei Dan groups and atorvastatin group were decreased(P<0.01),while the level of HDL-C increased(P<0.01).The mRNA levels and con-tent of IL-1β,IL-6 and TNF-α in Anmei Dan groups and atorvastatin group were decreased(P<0.01).The expression of GluR1,PSD-95,BDNF and p-CaMKⅡ in hippocampal tissue of Anmei Dan groups were increased(P<0.01),and the expression of Arc was decreased(P<0.01).The morphology and structure of the cells in the Anmei Dan group and the atorvastatin group were improved,with varying degrees of increased Nissl bodies and relatively intact cell membranes.CONCLUSION Anmei Dan can effectively im-prove blood lipids and depression-like behavior of coronary heart disease mice complicated with depression.It can inhibit pro-inflam-matory factors,increase the expression of neurotrophic factors,effectively improve synaptic related proteins,and reduce the damage to neurons,thus effectively preventing the exacerbation of coronary heart disease and depression comorbidity.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.