ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

Objective To investigate the correlation between coronary heart disease(CHD)and cognitive impairment in rural populations aged 40 and above.Methods From October 2014 to March 2015,all residents aged 40 and above from two villages in Huyi District,Xi'an,were selected as study subjects.Information regarding their demographics,lifestyle habits,medical history,family history,physical examinations,and biochemical tests was collected.The participants were categorized into those with and without the history of CHD.Cognitive function was assessed using the Mini-Mental State Examination(MMSE),with scores below the cutoff(illiteracy≤17;primary school≤20;junior high school and above≤24)defined as cognitive impairment.Chi-square test was used to compare the prevalence of cognitive impairment between the CHD and non-CHD groups.Multivariate Logistic regression was employed to adjust for confounding factors in analyzing the relationship between CHD and cognitive impairment.Results A total of 1 833 subjects were included in the analysis,comprising 735 males(40.1％)and 57 individuals with CHD(3.1％).Among them,234 participants(13.3％)met the criteria for cognitive impairment.Univariate analysis showed a higher prevalence of cognitive impairment in the CHD group compared to the non-CHD group(24.6％vs.12.9％,P=0.016).Unadjusted binary Logistic regression analysis indicated a positive correlation between CHD and cognitive impairment(OR=2.199,95％CI:1.185-4.084,P=0.013).However,after adjusting for confounding factors such as gender,age,education level,hypertension,diabetes,dyslipidemia,stroke history and BMI,the association between CHD and cognitive impairment was not statistically significant(OR=1.265,95％CI:0.656-2.441,P=0.483).In the stratified analysis,among diabetic patients,CHD was significantly associated with a high risk of cognitive impairment(OR=4.191,95％CI:1.464-12.000,P=0.008).The prevalence of cognitive impairment significantly increased in patients with CHD combined with diabetes(OR=4.712,95％CI:1.651-13.449,P=0.004).Conclusion This study did not establish a direct association between CHD and cognitive impairment.However,this study suggests that the presence of CHD and diabetes mellitus is significantly associated with an increased risk of cognitive impairment.Future prospective studies with larger sample sizes should be conducted to further confirm the relationship between the two.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

Epitope vaccine is a novel strategy for vaccine development in recent years,exhibiting ad-vantages such as safety,and the ability to induce specific humoral and cellular immune responses a-gainst pathogens.Among them,the identification and delivery of epitopes are crucial in the design of multi-epitope vaccines.Compared to traditional methods of antigenic epitope identification,vari-ous new techniques such as bioinformatics,ELIspot,and intracellular cytokine staining have been developed.Since the direct immunization of multi-epitope peptides results in low protective effica-cy,efficient delivery systems are urgently needed.The antigenic epitopes commonly used delivery systems include viral vectors,and non-virus vectors such as nanoparticles,etc.Additionally,to en-hance the immunization efficacy of vaccines,antigenic epitopes are usually modified,including mul-tiple epitopes in tandem and epitope targeting modification and other strategies.This review sum-marizes the methods for accurate identification of antigenic epitopes with well immunogenicity as well as effective delivery strategies for antigenic epitopes,providing new insight into the develop-ment of novel multi-epitope vaccines.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

Objective To investigate the correlation between coronary heart disease(CHD)and cognitive impairment in rural populations aged 40 and above.Methods From October 2014 to March 2015,all residents aged 40 and above from two villages in Huyi District,Xi'an,were selected as study subjects.Information regarding their demographics,lifestyle habits,medical history,family history,physical examinations,and biochemical tests was collected.The participants were categorized into those with and without the history of CHD.Cognitive function was assessed using the Mini-Mental State Examination(MMSE),with scores below the cutoff(illiteracy≤17;primary school≤20;junior high school and above≤24)defined as cognitive impairment.Chi-square test was used to compare the prevalence of cognitive impairment between the CHD and non-CHD groups.Multivariate Logistic regression was employed to adjust for confounding factors in analyzing the relationship between CHD and cognitive impairment.Results A total of 1 833 subjects were included in the analysis,comprising 735 males(40.1％)and 57 individuals with CHD(3.1％).Among them,234 participants(13.3％)met the criteria for cognitive impairment.Univariate analysis showed a higher prevalence of cognitive impairment in the CHD group compared to the non-CHD group(24.6％vs.12.9％,P=0.016).Unadjusted binary Logistic regression analysis indicated a positive correlation between CHD and cognitive impairment(OR=2.199,95％CI:1.185-4.084,P=0.013).However,after adjusting for confounding factors such as gender,age,education level,hypertension,diabetes,dyslipidemia,stroke history and BMI,the association between CHD and cognitive impairment was not statistically significant(OR=1.265,95％CI:0.656-2.441,P=0.483).In the stratified analysis,among diabetic patients,CHD was significantly associated with a high risk of cognitive impairment(OR=4.191,95％CI:1.464-12.000,P=0.008).The prevalence of cognitive impairment significantly increased in patients with CHD combined with diabetes(OR=4.712,95％CI:1.651-13.449,P=0.004).Conclusion This study did not establish a direct association between CHD and cognitive impairment.However,this study suggests that the presence of CHD and diabetes mellitus is significantly associated with an increased risk of cognitive impairment.Future prospective studies with larger sample sizes should be conducted to further confirm the relationship between the two.

Epitope vaccine is a novel strategy for vaccine development in recent years,exhibiting ad-vantages such as safety,and the ability to induce specific humoral and cellular immune responses a-gainst pathogens.Among them,the identification and delivery of epitopes are crucial in the design of multi-epitope vaccines.Compared to traditional methods of antigenic epitope identification,vari-ous new techniques such as bioinformatics,ELIspot,and intracellular cytokine staining have been developed.Since the direct immunization of multi-epitope peptides results in low protective effica-cy,efficient delivery systems are urgently needed.The antigenic epitopes commonly used delivery systems include viral vectors,and non-virus vectors such as nanoparticles,etc.Additionally,to en-hance the immunization efficacy of vaccines,antigenic epitopes are usually modified,including mul-tiple epitopes in tandem and epitope targeting modification and other strategies.This review sum-marizes the methods for accurate identification of antigenic epitopes with well immunogenicity as well as effective delivery strategies for antigenic epitopes,providing new insight into the develop-ment of novel multi-epitope vaccines.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.