Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, its therapeutic potential and mechanisms against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we evaluated the in vivo neuroprotective effects of indobufen through both pretreatment and posttreatment regimens in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vitro, human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were employed to investigate the relationship between indobufen and the pyroptosis-associated NF-κB/Caspase-1/GSDMD pathway. The pharmacodynamic tests revealed that indobufen ameliorated I/R injury by decreasing the level of thromboxane B2 (TXB2), infarct size, brain edema and neurological impairment in rats and rescuing cell pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway. Overall, these studies indicate that indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

Prostate cancer is one of the most common malignant tumors of male genitourinary system. Prostate cancer has the following characteristics： insidious onset， early asymptomatic or not obvious symptoms， complex etiology and pathogenesis， long incubation period and so on. Therefore， the realization of its early diagnosis and treatment is of great significance to the prognosis of patients. Prostate-specific membrane antigen （PSMA） is a type 2 transmembrane glycoprotein that is highly expressed on the membrane of almost all primary and metastatic prostate cancer cells， and is an ideal target for prostate cancer imaging and treatment. In recent years， with the approval of urea-containing small molecule PET （positron emission computed tomography） radiopharmaceutical based on PSMA （⁶⁸Ga-PSMA-11， ¹⁸F-PSMA-1007）， PET-CT （positron emission computed tomography/computed tomography） has shown new potential for early diagnosis and accurate staging of prostate cancer patients. This review mainly summarizes the research progress of urea-containing PSMA PET imaging agents and finds that they have defects such as uptake in non-target tissues like the kidneys， lacrimal glands， and salivary glands. Thus， further optimizing their structure to reduce the uptake in non-target tissues， providing provide convenience for the labeling of therapeutic radiopharmaceuticals， thereby achieving the goal of integrated diagnosis and treatment， is an important development direction in this field.

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.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Objective To improve the analysis method of the blood components of Yinchenhao decoction （YCHD） in vivo and explore its anti-hepatocellular carcinoma mechanism. Methods Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS） was used to collect and analyze blood samples from mice. The mice were given a single dose of YCHD with a concentration of 0.1 g/ml and a dose of 25 ml/kg, and then the samples were collected 2 h post–administration, which was to systematically study the chemical components of YCHD in vivo. Network pharmacological methods were used to screen the components and targets of YCHD, and the targets of hepatocellular carcinoma; The common targets of YCHD and hepatocellular carcinoma were identified for GO enrichment and KEGG enrichment. Molecular docking was performed on the main targets to verify the binding ability between the active ingredients and the core targets. The relative mRNA expression levels of serine/threonine-protein kinase（AKT1） and tumor protein p53（TP53） in liver tissues were analyzed via qPCR, including the following mouse groups: mice with concanavalin A（Con-A）-induced acute liver injury without preventive administration, mice with Con-A-induced acute liver injury that received 14 d preventive oral administration of YCHD, and untreated control mice. Results ①The active ingredients of YCHD in the blood were identified by retrieving the data from the in vitro component analysis. They were chrysophanol, herniarin, aloe-emodin, and monotropein. ②The mechanism of action of the blood components against hepatocellular carcinoma （HCC） was further analyzed using network pharmacological methods, and a total of 30 components of YCHD were screened for 213 targets and 215 HCC targets. ③There were 17 intersection targets between YCHD and hepatocellular carcinoma, including AKT1, TP53, receptor tyrosine-protein kinase erbB-2 （ERBB2）, myelocytomatosis oncogene （MYC）, interleukin-1β （IL-1β）, etc. The GO enrichment results indicated that these components were primarily involved in DNA replication，chromosome segregation，leukocyte mediated immunity，leukocyte cell-cell adhesion. The KEGG enrichment results demonstrated that these components were predominantly associated with diverse cancer pathways. Additionally, the results indicated involvement in the citrate cycle （TCA cycle）, pyruvate metabolism, and p53 signaling pathway, ect. ④The results of molecular docking showed that chrysophanol, herniarin, and aloe - emodin had strong binding abilities with AKT1, TP53, ERBB2, MYC, and IL-1β. ⑤The relative expression of AKT1 and TP53 mRNA was significantly higher in the modelling group than in the control group. The relative expression of AKT1 and TP53 mRNA was significantly lower in the drug administration group than in the modelling group. Conclusion There were 4 blood components in YCHD, among which chrysophanol, herniarin, and aloe-emodin may act on AKT1, TP53, ERBB2, MYC, IL-1β and then participated in the regulation of cancer signaling pathways and p53 signaling pathway to play a role in the treatment of HCC.

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.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Objective: To investigate the factors affecting cognition and vaccination willingness to receive human papilloma virus (HPV) vaccine among male university students, so as to provide a basis for formulating health education and promotion strategies for HPV vaccination in males. Methods: From March to June 2025, a convenience sampling method was used to recruit full-time male undergraduate students from 23 universities in Zhejiang Province. Self-administered questionnaires were employed to collect information on participants' basic demographics, sexual behaviors, knowledge of HPV and HPV vaccines, and willingness to receive HPV vaccination. Multivariable logistic regression model was used to analyze the influencing factors for vaccination willingness to receive HPV vaccine among male university students. Results: A total of 402 male university students were surveyed, with a mean age of (20.20±1.95) years. Among them, 65 participants reported having engaged in sexual behavior, accounting for 16.17%. Additionally, 192 students perceived themselves to be at relatively high risk of HPV infection, accounting for 47.76%. Knowledge of HPV and the HPV vaccine was reported by 227 participants, corresponding to an awareness rate of 56.47%. Willingness to receive HPV vaccine was expressed by 242 individuals, reflecting a vaccination willingness rate of 60.20%. Multivariable logistic regression analysis showed that male university students who were medical majors (OR = 3.404, 95% CI: 1.396-8.301), had engaged in sexual behavior (OR = 2.341, 95% CI: 1.102-4.970), perceived themselves to be at higher risk of HPV infection (OR = 1.631, 95% CI: 1.041-2.557), recognized the necessity of HPV vaccination for males (OR = 8.955, 95% CI: 4.705-17.044), and had been exposed to HPV vaccine promotion activities in their university (OR = 2.277, 95% CI: 1.320-3.926) showed a higher willingness to receive HPV vaccine. Conversely, those who had concerns about vaccine safety (OR = 0.510, 95% CI: 0.292-0.890), were unaware of the HPV vaccine appointment process (OR = 0.400, 95% CI: 0.232-0.690), or expressed concerns about the cost of the vaccine (OR = 0.560, 95% CI: 0.322-0.976) exhibited a lower willingness to be vaccinated. Conclusions Male university students in Zhejiang Province demonstrated a relatively low level of cognition regarding HPV and HPV vaccine, yet expressed a comparatively high willingness to receive HPV vaccine. Factors affecting vaccination willingness to receive HPV vaccine among male university students included cognition of HPV and HPV vaccine, self-perceived risk of HPV infection, concerns about vaccine safety, awareness of the vaccine appointment process, and considerations regarding vaccine cost.

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.