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

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.

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.

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.

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 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.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Objective To explore the cut-off value of three dimensional(3D)vena contracta area(VCA)in diagnosing severe tricuspid regrugitation(TR)under different etiologies and its accuracy and practicality in clinical application.Methods From Mar 2019 to May 2021,ninety-two patients with confirmed TR underwent two dimensional(2D)and 3D transthoracic echocardiography.The correlation and consistency between 3D VCA 3D calculated based on the proximal isokinetic surface area(PISA)effective regurgitant orifice area(EROA)was calculated.Comprehensive 2D multi-parameter method was used as a reference method to calculate the cut-off value of the diagnosis of severe TR.Results A total of 85 patients were ultimately included.3D VCA and 3D PISA EROA had similar and acceptable correlations in both primary TR and secondary TR(primary TR:r=0.831,P<0.01;secondary TR:r=0.806,P<0.01).Bland-Altman analysis showed that 3D VCA overestimated TR compared with 3D PISA EROA(62%overestimated in the total patient population,51%overestimated in primary TR,and 74%overestimated in secondary TR).In secondary TR,the cut-off value of 3D VCA for diagnosing severe TR was 0.45 cm2(sensitivity 89%,specificity 82%);combining clinical symptoms,positive 2D PISA EROA results and 3D VCA results for severe TR,the chi-square value was higher than those only included clinical symptoms or incorporated clinical symptoms and positive 2D PISA EROA results(42.168 vs.26.059 and 16.759,P<0.01).Conclusion 3D VCA would overestimate TR,and had high and incremental diagnostic value for evaluating severe TR in secondary TR.

Objective To explore the role of quality control circle in reducing the rate of extravasation during"bolus-type"intravenous injection of radiopharmaceuticals.Methods A total of 624 patients who underwent emission computed tomography(ECT)examinations were retrospectively selected as the pre-quality control circle use analysis group,125 patients who underwent ECT examinations were selected as the post-quality control circle use experiment group,and 70 patients were selected as the control group.This study applied the continuous quality improvement tools of the quality control circle,including grasping the current situation,selecting injection tools,personnel training,brainstorming,root cause analysis,key factor evaluation,true cause verification,strategy formulation and measure implementation,to continuously improve the quality of"bolus-type"radioisotope injection and reduce the rate of radiopharmaceuticals extravasation.Results In the experiment group,the rate of radioisotope extravasation after nurses performed"bolus-type"intravenous injection was 14.2％,compared to 33.3％in the control group,an improvement of 19％,and the situation of radiopharmaceuticals extravasation was significantly improved.Skillful use of quality improvement tools,especially in areas such as insufficient compression time,improper compression method,slow blood flow speed in fine blood vessels,and failed puncture,was crucial for radioisotope sur-face imaging.Conclusion Through continuous quality improvement by the quality control circle,this study successfully reduces the rate of extravasation during"bolus-type"intravenous injection of radiopharmaceuticals,reduces skin contamination,and improves the quality of nuclear medicine images,which is of great significance for improving the safety and diagnostic accuracy of nuclear medicine ECT examinations.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis