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.

ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

ObjectiveTo address the shortage of high-caliber multidisciplinary professionals in China's rehabilitation engineering field and the prominent issue of "separation between medicine and engineering" in existing curricula, this study introduces the World Health Organization rehabilitation competency framework (RCF) to construct a systematic curriculum system for rehabilitation engineering. MethodsGuided by the four core competency domains of RCF (practice, professionalism, learning and development, management and leadership) and their associated supporting knowledge, the rehabilitation engineering curriculum was restructured into a modular framework, piloted and validated within the Biomedical Engineering (Intelligent Robotics) program at University of Health and Rehabilitation Sciences. ResultsA four-tiered curriculum system comprising General Education-Disciplinary Platform-Professional Core-Diverse Electives with a total of 160 credits was established, achieving precise mapping between competency objectives and course content. The students in the pilot cohort demonstrated outstanding academic performance (50% ranked in the top ten of their major), they also gained a deeper understanding and mastery of interdisciplinary knowledge integrating medicine and engineering. ConclusionThe RCF-based curriculum system effectively promotes the organic integration of medical and engineering knowledge, providing an internationally aligned competency-oriented paradigm for rehabilitation engineering talent cultivation, which holds significant value for broader application.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.

ObjectiveTo compare the hepatic bile acid profile between a mouse model of metabolic-associated steatohepatitis （MASH） induced by a high-fat， high-sugar， and high-cholesterol diet combined with intraperitoneal injection of 10% carbon tetrachloride （CCl₄） and MASH cases in clinical practice， and to investigate the feasibility of this model in studying drug interventions on bile acid profile in MASH. MethodsA total of 30 male C57BL/6J mice were randomly divided into control group and model group， with 15 mice in each group. The mice in the control group were given normal diet and drinking water and weekly injections of olive oil， and those in the model group were given a high-fat， high-sugar， and high-cholesterol diet， high-sugar drinking water， and weekly injections of CCl₄+olive oil. At the end of weeks 8， 12， and 16， 5 mice were selected from each group to collect samples. Behavioral assessments were performed， and body weight and liver wet weight were measured； liver pathology and lipid deposition were evaluated by HE staining， SAF scoring， oil Red O staining， the semi-quantitative analysis of stained area， the serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， and liver triglyceride （TG） content； Sirius Red staining was performed for liver tissue to assess liver fibrosis； ultra-performance liquid chromatography-tandem mass spectrometry and targeted metabolomics were used to measure the hepatic bile acid profile， including cholic acid （CA）， glycocholic acid （GCA）， chenodeoxycholic acid （CDCA）， glycochenodeoxycholic acid （GCDCA）， ursodeoxycholic acid （UDCA）， tauroursodeoxycholic acid （TUDCA）， hyodeoxycholic acid （HDCA）， and glycodeoxycholic acid （GDCA）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the control group at the same time point， the model group had disheveled and dull fur， reduced activity， and relatively slow reactions at weeks 8， 12， and 16， as well as significant increases in liver wet weight （P<0.05）， the serum level of ALT （P<0.05）， the content of TG in the liver （P<0.05）， and SAF score （P<0.05）. As for the differentially expressed bile acids in liver tissue， compared with the control group at week 8， the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA， TUDCA， HDCA， and GDCA （all P<0.05）； compared with the control group at week 12， the model group had significantly higher levels of CA， GCA， CDCA， and GCDCA and significantly lower levels of UDCA and HDCA （all P<0.05）； compared with the control group at week 16， the model group had significantly higher levels of CA， GCA， CDCA， GCDCA， and TUDCA and significantly lower levels of UDCA， HDCA， and GDCA （all P<0.05）. As for the differentially expressed bile acids in the bile acid pool of liver tissue， compared with the control group at week 8， the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA， TUDCA， GDCA， and HDCA （all P<0.05）； compared with the control group at weeks 12 and 16， the model group had significantly higher levels of GCA and GCDCA and significantly lower levels of UDCA， GDCA， and HDCA （all P<0.05）. ConclusionThere are significant changes in the hepatic bile acid profile in a mouse model of MASH induced by a high-fat， high-sugar， and high-cholesterol diet combined with CCl₄， which are similar to the changes in bile acids in MASH cases in clinical practice， suggesting that this model can be used to explore the interventional effect of drugs on the bile acid profile in MASH.

To investigate body composition and associated factors in adolescents undergoing long-term regular sports training.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

To summarize the nursing experience of a patient with Danon disease after heart transplantation.Nursing key points:closely monitor heart function,prevent right heart failure;phased analgesic and sedative measures were implemented to reduce the occurrence of related complications.Skeletal muscle function was evaluated and rehabilitation training was strengthened to promote the prognosis of patients.The patient was transferred to the general ward 5 days after operation,and was discharged 22 days after operation.