ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the efficacy and mechanism of Euphorbia humifusa on acute kidney injury （AKI） based on network pharmacology， molecular docking and experimental verification. MethodsThe active components and targets of E. humifusa were retrieved from TCMSP and SwissTargetPrediction database， and the AKI targets were screened by GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. The drug targets and disease targets were intersected to construct a protein-protein interaction network， and the intersection targets were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. Discover Studio software was used to verify the molecular docking of key components and core targets. Gentamicin （GM） was used to induce AKI rat model. Control group， model group， verapamil （16 mg·kg^-1） group， E. humifusa extract （18， 54， 162 mg·kg^-1·d^-1） group and E. humifusa 70% ethanol extract （423 mg·kg^-1） group were continuously administered for 14 days. Urine volume was detected 24 h after modeling and administration. Serum creatinine （SCr）， Blood urea nitrogen （BUN）， 24-hour urine protein （24 hUTP） and uric acid （UA） content； the contents of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， carbon monoxide synthase （NOS） and lactate dehydrogenase （LDH） in kidney were measured. The levels of interleukin （IL）-6 and tumor necrosis factor （TNF）-α in serum were detected by enzyme linked immunosorbent assay（ELISA） kit. The pathological changes of renal tissue were detected by hematoxylin-eosin （HE） and Masson staining. Western blot was used to detect the expression of PI3K/protein kinase B（Akt）/NF-κB signaling pathway-related proteins. ResultsIn this study， 13 active components such as kaempferol， luteolin， apigenin， gallic acid and quercetin were screened and identified from E. humifusa. Through bioinformatics analysis， these components and AKI have a total of 289 targets， of which 62 are core targets， including Akt1， TNF， tumor protein p53（TP53） and IL-1β. These targets are mainly involved in the regulation of biological processes such as NF-κB signaling pathway， HIF-1 signaling pathway， TNF signaling pathway， PI3K/Akt signaling pathway and mitogen-activated protein kinase（MAPK） signaling pathway. In animal experiments， we successfully constructed a GM-induced AKI model in rats. Compared with the model group， E. humifusa extract could significantly reduce the levels of 24 hUTP， BUN and SCr in rats （P<0.01）， indicating its improvement effect on renal function. In addition， the extract of E. humifusa also significantly reduced LDH activity and MDA content in rat kidney tissue （P<0.05， P<0.01）， and significantly increased SOD， NOS activity and GSH content （P<0.05）， indicating that the extract of E. humifusa has the potential of anti-oxidation and protection of renal function. Further analysis of inflammatory factors showed that the levels of IL-6 and TNF-α in serum of rats treated with E. humifusa extract were significantly decreased （P<0.01）， indicating that E. humifusa extract had anti-inflammatory effects. In addition， the extract of E. humifusa can also regulate the protein expression of PI3K/Akt/NF-κB signaling pathway， which further confirmed its mechanism of reducing GM-induced AKI. ConclusionThe extract of E. humifusa has a significant therapeutic effect on acute kidney injury through its multi-component and multi-target mechanism. Its effect is reflected in improving renal function， anti-oxidation， anti-inflammation and regulating immune response. These findings provide a scientific basis for the application of E. humifusa in the treatment of acute kidney injury， and point out the direction for future drug development and clinical research.

ObjectiveTo identify key ligand-receptor axes that may improve immunotherapeutic strategies for hepatocellular carcinoma with portal vein tumor thrombus （PVTT）. MethodsSingle-cell RNA sequencing （scRNA-seq） data from normal tissues （Norm） and PVTT cells were downloaded from the gene expression omnibus （GEO） database， integrated， and annotated. CellChat was used to infer intercellular communication and compare pathway activities to screen significantly differential candidate ligand-receptor axes. Multiplex immunofluorescence （mIF） was then performed to evaluate the spatial distribution of signals related to candidate axes at the tissue level. The expression of key ligands and receptors was validated by qPCR and flow cytometry in peripheral blood-derived CD8⁺ T cells and the human hepatic stellate cell line LX-2. Functional effects were further assessed in vitro using recombinant proteins and antagonists or neutralizing blockers. ResultsThe analysis revealed strong bidirectional communication between CD8⁺ T cells and activated hepatic stellate cells （aHSCs） in PVTT. The SPP1-CD44 axis was the most prominent in the direction from CD8⁺ T cells to aHSCs， whereas the MIF-（CD74+ CD44） axis was strongly supported in the opposite direction. These axes were consistently supported by bioinformatic screening， tissue spatial analysis， and cellular or functional validation. ConclusionThe SPP1-CD44 and the MIF-（CD74+ CD44） axes may collectively shape the immunosuppressive tumor microenvironment （ITME） of PVTT through stromal activation and T-cell functional reprogramming， suggesting potential targets for improving immunotherapeutic responsiveness in patients with PVTT.

OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

Objective:To identify the main components of Huanglian Jiedu Decoction(HLJDD)using ultra-high-performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS),and to explore the potential mechanism of action of HLJDD in the treatment of gouty arthritis(GA)using network pharmacology and molecular docking methods.Methods:We identi-fied the chemical components of HLJDD by combining UPLC-Q-TOF-MS data acquired in both positive and negative ion modes with reference standards,relevant literature,and database searches.We analyzed the potential therapeutic mechanism of HLJDD for GA by using network pharmacology to determine the intersection targets between the active ingredients of HLJDD and GA for further enrich-ment analysis and visual network mapping.The binding affinity of the active ingredients with the intersection targets was validated through molecular docking.Results:A total of 47 components were identified by UPLC-Q-TOF-MS;54 key components of HLJDD for GA treatment and 37 intersection targets were determined by net-work pharmacology;and the top 10 key targets by Degree value were obtained by protein-protein interaction analysis.The Gene On-tology functional enrichment analysis revealed 20 biological pro-cesses,7 cellular components,and 8 molecular functions.The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated 96 GA-related intervention pathways,in which inflammatory signaling pathways such as interleukin-17(IL-17)and tu-mor necrosis factor(TNF)were involved.Molecular docking verified that the key components of HLJDD had high binding affinity with the core targets.Conclusion:The identified key components in HLJDD,such as phellodendrine,coptisine,wogonin,and β-sitosterol,may alleviate GA by regulating multiple core targets in the IL-17 and TNF pathways,such as PTSG2,which provides a theoretical ba-sis for future investigation into the mechanism of action of HLJDD.

Sepsis refers to a life-threatening organ dysfunction caused by a dysregulated host response to infection,with persistently high morbidity and mortality,posing a significant healthcare burden.As integral components of innate and adaptive immunity,macrophages exhibit high plasticity and can differentiate into distinct phenotypes(M1 pro-inflammatory and M2 anti-inflammatory)in response to various environmental stimuli,playing crucial roles in both the hyperinflammatory phase and late immunosuppressive phase of sepsis.The metabolic profile of M2 macrophages has gradually become a research focus,and it is regulated by a variety of enzymes and signaling pathways,including adenosine 5'-monophosphate-activated protein kinase,peroxisome proliferator-activated receptor and protein kinase RNA-like ER kinase pathways.These pivotal signaling pathways and enzymes can promote the polarization of M2 macrophages and enhance their anti-inflammatory functions by modulating the metabolism of glucose,lipid,and amino acid,thereby conferring protective effects against sepsis and providing new ideas for the targeted treatment.

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Objective To investigate the clinical characteristics,distribution of traditional Chinese medicine(TCM)syndrome types,and the anxiety and depression status in patients with colorectal polyps.Methods From January 2022 to December 2023,a total of 200 cases of patients with colorectal polyps(polyp group)and 100 patients without intestinal abnormalities(non-polyp group)under colonoscope who received colonoscopy or treatment at the Endoscopy Center of Dongguan Hospital,Guangzhou University of Chinese Medicine were enrolled.The relevant medical information of the patients in the two groups were collected,and then TCM syndrome differentiation of patients with colorectal polyps were carried out,the general infromation including gender,age,body mass index(BMI),smoking history and alcohol-intake history was recorded,and Hospital Anxiety and Depression Scale(HAD)score was calculated for assessing their anxiety and depression status.Results(1)The investigation of clinical characteristics showed that between the polyp group and the non-polyp group,the differences in the general information of gender,age,BMI,smoking history and alcohol-intake history were statistically significant(P<0.05 or P<0.01).As for the gender,the polyp group was predominated by the male(63.5%),while the non-polyp group was predominated by the female(58.0%),indicating that male patients were more likely to suffer from colorectal polyps.In terms of the age,the age group of 51-60 years old accounted for a higher percentage(36.0%)in the polyp group,while the age group of 41-50 years old accounted for a higher percentage(38.0%)in the non-polyp group,indicating that the polyp group had an elder average age than the non-polyp group.In addition,the percentages of patients with obesity(BMI≥28.0 kg/m2),smoking history,and alcohol-intake history in the polyp group were higher than those in the non-polyp group.(2)The analysis of features of colorectal polyps showed that the polyps were mostly seen in the left colon,accounting for 53.5%in the polyp group;adenomatous polyps accounted for 57.0%of all polyps;the size of colorectal polyps was usually less than one centimeter,accounting for 81.5%of all polyps;single colorectal polyps accounted for 45.5%,and multiple colorectal polyps accounted for 54.5%,indicating that colorectal polyps were usually multiple.(3)Among the 200 patients with colorectal polyps,there were 93 cases of syndrome of stagnation dampness due to spleen deficiency(46.5%),59 cases of dampness-heat in large intestine syndrome(29.5%),27 cases of liver depression and qi stagnation syndrome(13.5%),and 21 cases of dampness and blood stasis obstruction syndrome(10.5%).There were no statistically significant differences in the distribution of TCM syndrome types among colorectal polyp patients with different genders,ages,BMIs and alcohol consumption(P>0.05).The difference in the distribution of TCM syndrome types among colorectal polyp patients with or without smoking history was statistically significant(P<0.05).No statistically significant differences were shown in the distribution of TCM syndrome types among the colorectal polyp patients with various foci,number of polyps,and pathological types(P>0.05).The difference in the distribution of TCM syndrome types in colorectal polyp patients with different polyp sizes was statistically significant(P<0.05).In the patients with the polyp size0.05).In addition,the differences of anxiety scores and depression scores in the patients with various TCM syndrome types were not statistically significant(P>0.05).Conclusion(1)The distribution of TCM syndrome types of colorectal polyps is predominated by the syndrome of stagnation dampness due to spleen deficiency and dampness-heat in large intestine syndrome.The distribution of TCM syndrome types has no correlation with anxiety and depression,and the polyp foci,number of polyps,and pathological types of polyps,but has certain correlation with the size of the polyps.(2)Anxiety and depression may be the risk factors for colorectal polyps,but the polyp foci,number of polyps,and pathological types of polyps have no correlation with anxiety and depression,and the size of polyps may have certain correlation with anxiety.(3)Gender,age,smoking history and alcohol-intake history may be the risk factors for colorectal polyps.

Objective To evaluate the clinical efficacy of Gushang External Wash Granules combined with extracorporeal shockwave therapy(ESWT)in treating early-to-middle-stage knee osteoarthritis(KOA)with cold-damp obstruction syndrome.Methods A total of 84 patients diagnosed as early-to-middle-stage KOA(cold-damp obstruction syndrome)at the Orthopedic Outpatient Clinic of Dongguan Hospital of Guangzhou University of Chinese Medicine(Dongguan Traditional Chinese Medicine Hospital)from July 2022 to July 2023 were enrolled.Patients were randomly assigned to either the observation group or control group using a random number table,with 42 cases in each group.Both groups received ESWT,while the observation group additionally underwent topical washing with Gushang External Wash Granules.The treatment course lasted 4 weeks for both groups.The changes in traditional Chinese medicine(TCM)syndrome scores,Visual Analogue Scale(VAS)scores for pain,and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores in the two groups were measured before and after treatment,and the clinical efficacy was evaluated after treatment.Results(1)After 4 weeks of treatment,the total effective rate was 95.24%(40/42)in the observation group versus 76.19%(32/42)in the control group.Intergroup comparison(tested by chi-square test)showed significantly superior efficacy in the observation group(P＜0.05).(2)After treatment,both groups demonstrated significant reductions in VAS pain scores compared to those before treatment(P＜0.01),while no statistically significant difference was found between groups(P＞0.05).(3)WOMAC scores were decreased significantly in both groups after treatment(P＜0.01),and the observation group showed significantly greater reduction than the control group(P＜0.01),with statistically significance.(4)After treatment,the scores for the TCM symptoms of intolerance of cold and limb chilling,restricted flexion-extension,and stiffness and numbness in the extremities were significantly reduced in both groups(P＜0.01),and the observation group demonstrated significantly greater improvements in all TCM syndrome scores than the control group(P＜0.01).Conclusion The combination of Gushang External Wash Granules and ESWT demonstrates significant efficacy for the patients with early-to-middle-stage KOA of cold-damp obstruction type,and is effective on alleviating clinical symptoms and improving knee function and quality of life of the patients.