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.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

OBJECTIVE To clarify the current development status of clinical pharmacist training bases and the pharmacist workforce in China， and to provide evidence for standardizing base construction and promoting the high-quality development of hospital pharmacy. METHODS Questionnaires were distributed to all clinical pharmacist training bases for urgently-needed health professionals and clinical pharmacist training bases under the Chinese Hospital Association that had been approved by the end of 2023 to collect data including base profiles and pharmacist staffing conditions. Expert teams carried out field investigations to verify the collected data. Descriptive statistical analyses were conducted on the quantity， type and regional distribution of training bases， and the influencing factors of pharmacist staffing in the bases were analyzed. RESULTS Field surveys were completed covering 297 training bases across 31 provincial-level administrative regions. Among the base hospitals， 87.88% were Grade A tertiary general hospitals， and 65.32% were located in provincial capitals. The eastern region had the largest number of bases （136， accounting for 45.79%）， followed by the western region （79， 26.60%）. Great disparities existed among provinces in terms of base quantity and hospital scale. The median proportion of pharmaceutical technical personnel in base hospitals was 4.05%， and the median number of clinical pharmacists per 100 hospital beds was 0.53. Both indicators reached the highest in the eastern region （0.57， 4.43%） and the lowest in the northeastern region （0.45， 3.01%）. A total of 3 627 full-time clinical pharmacists were employed in all surveyed bases， among whom 83.68% held clinical pharmacist training certificates， 35.43% possessed senior professional titles， and 78.19% had postgraduate or higher educational background. The total annual training capacity of the surveyed bases was 4 291 trainees， with obvious differences in annual training capacity across regions and provinces. Training specialties covered 19 specialized disciplines plus one general discipline， and no province could deliver training for all 20 specialties simultaneously. Multivariate Logistic regression analysis showed that geographic region exerte d a significant impact on the proportion of pharmaceutical technical personnel （≥4%） （ P ＜0.05）， while the approval time of training bases and hospital scale had significant effects on the number of clinical pharmacists per 100 beds （≥0.6） （ P ＜0.05）. CONCLUSIONS China’s clinical pharmacist training system has basically matured and taken initial shape. The distribution of clinical pharmacist training resources is generally consistent with regional population and economic development levels. However， the allocation of pharmaceutical staff and clinical pharmacists has not yet met national standards and clinical service demands.

OBJECTIVE To clarify the current development status of clinical pharmacist training bases and the pharmacist workforce in China， and to provide evidence for standardizing base construction and promoting the high-quality development of hospital pharmacy. METHODS Questionnaires were distributed to all clinical pharmacist training bases for urgently-needed health professionals and clinical pharmacist training bases under the Chinese Hospital Association that had been approved by the end of 2023 to collect data including base profiles and pharmacist staffing conditions. Expert teams carried out field investigations to verify the collected data. Descriptive statistical analyses were conducted on the quantity， type and regional distribution of training bases， and the influencing factors of pharmacist staffing in the bases were analyzed. RESULTS Field surveys were completed covering 297 training bases across 31 provincial-level administrative regions. Among the base hospitals， 87.88% were Grade A tertiary general hospitals， and 65.32% were located in provincial capitals. The eastern region had the largest number of bases （136， accounting for 45.79%）， followed by the western region （79， 26.60%）. Great disparities existed among provinces in terms of base quantity and hospital scale. The median proportion of pharmaceutical technical personnel in base hospitals was 4.05%， and the median number of clinical pharmacists per 100 hospital beds was 0.53. Both indicators reached the highest in the eastern region （0.57， 4.43%） and the lowest in the northeastern region （0.45， 3.01%）. A total of 3 627 full-time clinical pharmacists were employed in all surveyed bases， among whom 83.68% held clinical pharmacist training certificates， 35.43% possessed senior professional titles， and 78.19% had postgraduate or higher educational background. The total annual training capacity of the surveyed bases was 4 291 trainees， with obvious differences in annual training capacity across regions and provinces. Training specialties covered 19 specialized disciplines plus one general discipline， and no province could deliver training for all 20 specialties simultaneously. Multivariate Logistic regression analysis showed that geographic region exerte d a significant impact on the proportion of pharmaceutical technical personnel （≥4%） （ P ＜0.05）， while the approval time of training bases and hospital scale had significant effects on the number of clinical pharmacists per 100 beds （≥0.6） （ P ＜0.05）. CONCLUSIONS China’s clinical pharmacist training system has basically matured and taken initial shape. The distribution of clinical pharmacist training resources is generally consistent with regional population and economic development levels. However， the allocation of pharmaceutical staff and clinical pharmacists has not yet met national standards and clinical service demands.

OBJECTIVE To investigate the current status of quality management in clinical pharmacist training bases in China， and to provide references for the standardized development and improvement of these bases. METHODS A combined approach of questionnaire survey and on-site investigation was adopted， targeting the healthcare highly sought-after talent （clinical pharmacist） training bases in 31 provinces of China as well as the clinical pharmacist training bases affiliated with the Chinese Hospital Association. A training quality management evaluation index system consisting of 25 tertiary indicators was established. Investigations were conducted from two dimensions： structural quality of training and quality management of training processes. Data were statistically analyzed using descriptive statistical methods. RESULTS On-site investigations were completed for 297 clinical pharmacist training bases across the 31 provinces， among which 284 were affiliated with the Chinese Hospital Association and 271 were healthcare highly sought-after talent （clinical pharmacist） training bases. In terms of structural quality， the core indicator compliance rate for hospital-level training systems exceeded 80%， the rate of special fund utilization for designated purposes reached 80.13%， and the overall compliance rate for software and hardware facilities surpassed 88%. A total of 1 348 preceptors were employed across the training bases， among whom those with senior professional titles and full-time specialist clinical pharmacists as lead preceptors accounted for 62.91% and 94.36%， respectively. Regarding process quality， the compliance rate for “establishment of clinical practice teaching groups in accordance with regulations during clinical department rotations” was 85.19%， and 79.80% and 76.09% of the bases were found to implement strict confidentiality in theoretical examinations and meet the required scale of assessment cases， respectively. However， formal documents of corresponding training management regulations were formulated in only 57.91% of the bases， and the completeness and standardization rate of training manual completion was merely 47.47%. In addition， considerable disparities in quality management levels were observed among provinces， with issues in training process quality being particularly prominent. CONCLUSIONS The management system， hardware facilities， and preceptor staffing of clinical pharmacist training bases in China are relatively well-established， yet notable variations in quality management exist among training bases across different provinces.

Objective:To explore the correlations between the monocytes/high-density lipoprotein ratio (MHR), alkaline phosphatase (ALP), and all-cause mortality in patients undergoing maintenance peritoneal dialysis (PD), and to provide references for clinical prevention and treatment strategies.Methods:A retrospective analysis was conducted on the clinical data of 336 PD patients who were treated in the Affiliated Hospital of Jining Medical University from June 2014 to August 2023. According to the survival status of the patients during the follow-up period, they were divided into the death group ( n=55) and the survival group ( n=281). The differences in clinical data, blood routine, laboratory biochemical indicators, monocyte count, high-density lipoprotein cholesterol, and ALP indicators between the two groups were collected and compared. Multivariate Cox regression analysis was used to screen the risk factors for all-cause mortality in PD patients, and Pearson correlation analysis was used to evaluate the correlation between the survival time of patients and related indicators. Results:In this study, there were 55 patients who died of all causes. The causes of death were cardiovascular events in 26 cases (47.27%), gastrointestinal bleeding in 3 cases (5.45%), infection in 7 cases (12.73%), multiple organ failure in 8 cases (14.55%), and unexplained death in 11 cases (20.00%). There was no statistically significant difference in gender, age, weight, serum parathyroid hormone (PTH), and total cholesterol (TC) between the death group and the survival group (all P>0.05). The treatment time, neutrophil count, red blood cell volume distribution width (RDW), ALP, blood uric acid (UA), blood calcium, MHR and creatinine in the death group were all higher than those in the survival group (all P<0.05), while the lymphocyte count was lower than that in the survival group ( P<0.05). The Cox risk model showed that MHR, ALP, treatment duration, neutrophil count, lymphocyte count, RDW, UA, and creatinine were independent risk factors for all-cause mortality in PD patients ( OR=1.578, 2.881, 1.021, 1.122, 1.476, 2.231, 1.018, 1.008, all P<0.05); Pearson correlation analysis revealed that the survival time of PD patients was negatively correlated with MHR and ALP ( r=-0.305, -0.246, all P<0.05). Conclusions:The levels of MHR and ALP are closely related to the risk of all-cause mortality in PD patients and are independent risk factors for all-cause mortality in patients.

Diabetic foot ulcer (DFU) have emerged as a serious global health issue due to its high rates of occurrence, disability, and mortality. DFU exhibit an exceptionally high recurrence rate, driven by a combination of behavioral and biological factors, leading to the recognition of fully epithelialized ulcers as being in "remission" rather than cured. However, the pathogenic factors underlying recurrent DFU (RDFU) remain poorly understood. This review examines the epidemiological characteristics and pathophysiological mechanisms of RDFU. Key mechanisms include neuropathy, angiopathy, epigenetic modifications, and metabolic memory. Research demonstrates that RDFU development results from the interplay of multiple factors: hyperglycemia-induced metabolic abnormalities, chronic inflammatory responses, vascular and neurological damage, as well as dysregulated epigenetic control. These factors interact synergistically, creating a vicious cycle that increases the risk of recurrence and delays recovery. By synthesizing current knowledge, this review aims to provide a foundation for future research and clinical management of RDFU. The insights presented support the development of personalized treatment strategies and effective preventive measures to reduce recurrence and improve patient outcomes.

Objective:To explore the correlations between the monocytes/high-density lipoprotein ratio (MHR), alkaline phosphatase (ALP), and all-cause mortality in patients undergoing maintenance peritoneal dialysis (PD), and to provide references for clinical prevention and treatment strategies.Methods:A retrospective analysis was conducted on the clinical data of 336 PD patients who were treated in the Affiliated Hospital of Jining Medical University from June 2014 to August 2023. According to the survival status of the patients during the follow-up period, they were divided into the death group ( n=55) and the survival group ( n=281). The differences in clinical data, blood routine, laboratory biochemical indicators, monocyte count, high-density lipoprotein cholesterol, and ALP indicators between the two groups were collected and compared. Multivariate Cox regression analysis was used to screen the risk factors for all-cause mortality in PD patients, and Pearson correlation analysis was used to evaluate the correlation between the survival time of patients and related indicators. Results:In this study, there were 55 patients who died of all causes. The causes of death were cardiovascular events in 26 cases (47.27%), gastrointestinal bleeding in 3 cases (5.45%), infection in 7 cases (12.73%), multiple organ failure in 8 cases (14.55%), and unexplained death in 11 cases (20.00%). There was no statistically significant difference in gender, age, weight, serum parathyroid hormone (PTH), and total cholesterol (TC) between the death group and the survival group (all P>0.05). The treatment time, neutrophil count, red blood cell volume distribution width (RDW), ALP, blood uric acid (UA), blood calcium, MHR and creatinine in the death group were all higher than those in the survival group (all P<0.05), while the lymphocyte count was lower than that in the survival group ( P<0.05). The Cox risk model showed that MHR, ALP, treatment duration, neutrophil count, lymphocyte count, RDW, UA, and creatinine were independent risk factors for all-cause mortality in PD patients ( OR=1.578, 2.881, 1.021, 1.122, 1.476, 2.231, 1.018, 1.008, all P<0.05); Pearson correlation analysis revealed that the survival time of PD patients was negatively correlated with MHR and ALP ( r=-0.305, -0.246, all P<0.05). Conclusions:The levels of MHR and ALP are closely related to the risk of all-cause mortality in PD patients and are independent risk factors for all-cause mortality in patients.

Objective:To develop an evidence-based nursing practice program based on the Stetler model to extend the lifespan of arteriovenous fistulas (AVF) in maintenance hemodialysis (MHD) patients and evaluate its effectiveness.Methods:An evidence-based nursing practice program was constructed based on the best evidence for extending AVF lifespan in MHD patients. Expert group discussions were held to determine review indicators. A baseline survey was conducted among 100 MHD patients and 42 nurses using covenience sompling at the Blood Purification Center of Wuxi People's Hospital from January to December 2023, to identify barriers and facilitators. In the following year, from January to December 2024, the evidence-based practice was implemented at the same hospital, and the AVF surgical intervention rate and AVF self-management levels of MHD patients were compared before and after the practice.Results:No statistically significant difference was found in the AVF surgery rates before and after the evidence-based practice ( P>0.05) . However, after implementing the evidence-based practice, MHD patients' scores on the AVF self-management scale significantly improved, and the difference was statistically significant ( P<0.01) . Conclusions:The evidence-based practice based on the Stetler model is beneficial for standardizing the clinical management of AVF, reducing the need for surgical interventions, and improving MHD patients' ability to self-manage their AVF.