Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Ultrasound technology has been applied in the biomedical field,particularly in drug delivery and cell processing.In this study,the effects of different ultrasound power levels(40 W to 100 W)and time durations(1 min,5 min,or 5 min discontinuously)on the morphology of human red blood cells(hRBCs)membranes were systematically investigated using cryo-electron tomography(Cryo-ET).The hRBCs membranes were firstly subjected to ultrasound at power levels of 40 W and 60 W for 5 min each.Cryo-ET observations revealed minimal morphological changes in the hRBCs membranes following the 40 W treatment,with the membrane structure remaining relatively intact and only minor undulations appearing on the membrane surface.These undulations might result from the mild mechanical stress induced by ultrasound,which was insufficient to disrupt the overall membrane structure.At power of 60 W,the hRBCs membranes largely preserved their structural integrity.When the ultrasonic power was increased to 80 W,the structural damage to the hRBCs membranes became more severe.Cryo-ET images showed irregular ruptures and larger pores on the membrane surface,indicating a significant compromise in membrane integrity.At ultrasound power of 100 W,the hRBCs membranes were completely disrupted,resulting in the formation of numerous membrane fragments,and a complete loss of membrane continuity.To further explore the effects of ultrasound duration on erythrocyte membrane morphology,the ultrasonic power was fixed at 100 W and the impacts of varying treatment durations(1 min,5 min,and intermittent ultrasound)on the membrane structure were systematically investigated.After 1 min of ultrasonic treatment,Cryo-ET images showed minimal changes in erythrocyte membrane morphology.Although some small pores and undulations appeared on the membrane surface,the overall structure remained relatively intact.As the ultrasound duration extended to 5 min,the degree of membrane damage increased significantly.Cryo-ET images revealed extensive rupture and detachment of the membrane,with continuity being severely compromised.As to treatment alternating 1 min of ultrasound with 1 min of rest,for a total of 5 min of ultrasound exposure,Cryo-ET observations showed the integrity of the membrane-cytoskeleton attachment remained.Under intermittent ultrasound treatment,although some pores and ruptures were observed on the membrane surface,the overall structure remained more intact compared to continuous ultrasonic treatment.This preservation might be due to the intermittent treatment providing buffer periods for the membrane,allowing partial recovery after mechanical stress,thereby reducing the cumulative damage caused by continuous ultrasound.This work provided experimental basis for further understanding of mechanism of ultrasound induced change of cell membrane and cytoskeleton.

A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1％and 119％,with relative standard deviations(RSDs)of 0.2％to 9.9％.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.

OBJECTIVE: Ulcerative colitis is closely associated with intestinal stem cell (ISC) loss and impaired intestinal mucus barrier. Sinisan (SNS), a compound Chinese herbal medicine, has a long history in the treatment of intestinal dysfunction, yet whether SNS can relieve acute experimental colitis by modulating ISC proliferation and secretory cell differentiation has not been studied. Our study tested the effect of SNS against acute colitis and focused on the mechanisms involving intestinal barrier recovery. METHODS: Network pharmacology analysis and blood entry component analysis of SNS were used to explore the underlying mechanism by which SNS affects the acute dextran sulfate sodium (DSS)-induced murine colitis model. RNA-sequencing was used to demonstrate the mechanism. Further, reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining, and alcian blue and periodic acid-Schiff staining were performed in vivo and in the colonic organoids to investigate the cell lineage differentiation-related mechanism of SNS. Furthermore, potential active ingredients from SNS were predicted by network pharmacology analysis. RESULTS: SNS dramatically suppressed DSS-induced acute colonic inflammation in mice. RNA-sequencing analysis revealed downregulation of inflammation and apoptosis-related genes, and upregulation of lipid metabolism and proliferation-related genes, such as Irf7, Pparα, Clspn and Hspa5. Additionally, ISC renewal and intestinal secretory cell lineage commitment were significantly promoted by SNS both in vivo and in vitro in colonic organoids, leading to enhanced mucin expression. Furthermore, potential active ingredients from SNS that mediated inflammation, lipid metabolism, proliferation, apoptosis, stem cells and secretory cells were predicted using a network pharmacology approach. CONCLUSION Our study shed light on the underlying mechanism of SNS in attenuating acute colitis from the perspective of ISC renewal and secretory lineage cell differentiation, suggesting a of novel therapeutic strategy against colitis. Please cite this article as: Cai YJ, Lan JH, Li S, Feng YN, Li FH, Guo MY, et al. Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production. J Integr Med. 2025; 23(4): 429-444.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Colon/pathology* ; Mucins/metabolism* ; Mice, Inbred C57BL ; Cell Differentiation/drug effects* ; Male ; Colitis/metabolism* ; Cell Lineage/drug effects* ; Dextran Sulfate ; Stem Cells/drug effects* ; Disease Models, Animal

Objective To investigate the value of conventional radiological features and CT radiomics fea-tures to differentiate parotid adenolymphoma from malignant tumor.Methods Radiological data from 128 patients with adenolymphoma and 39 patients with parotid malignancy were collected between December 2018 and October 2023.Radiomics features were extracted to obtain Rad-score and construct a radiomics model.Conventional radiologi-cal features were analyzed to obtain independent predictors,and a conventional radiological model was constructed.Model performance was compared by the DeLong test,and the Rad-score was combined with radiological features to establish a comprehensive model and plot a nomogram.Results Based on CT venous phase images,9 optimal radiomic features were selected.Conventional radiological features were analyzed by univariate and multivariate logistic regression analysis and found that shape and degree of enhancement were independent predictors of adenolymphoma and malignant parotid tumors.The CT radiomics model is superior to the conventional radiological model(P<0.05).The area under the curve(AUC)of the radiomics model was 0.938(95%CI:0.887～0.988),and the specificity and sensitivity were 0.856 and 0.923,respectively.Conventional radiological features and Rad-score were analyzed by univariate and multivariate logistic regression analysis and found that Rad-score and degree of enhancement were independent predictors of adenolymphoma and malignant parotid tumors.The difference between the diagnostic efficacy of the comprehensive model created by the Rad-score combined with the degree of enhancement and the diagnostic efficacy of the radiomics model was not statistically significant(P>0.05).Conclusion The CT radiomics model per-formed better than the conventional radiological model in discriminating parotid gland adenolymphoma from malignant tumors.The diagnostic performance of the comprehensive model has improved,aiding in clinical decision-making.

Objective:To prepare mesothelin-loaded paclitaxel (PTX) phase change nanoparticles and evaluate their targeting effect and therapeutic effect on ovarian cancer.Methods:PTX-loaded phase-change nanoparticles PTX-NPs were prepared by the thin-film hydration method, and targeted mesothelin-loaded PTX phase-change nanoparticles Ab-PTX-NPs were prepared by attaching anti-mesothelin antibody to the nanoparticles using the biotin-affinity method. Zeta potential and particle size were determined by applying a zeta potential and a particle size analyzer, and the encapsulation rate and the amount of drug loading of PTX was measured by applying a UV spectrophotometer. Flow cytometry was used to detect the connectivity of anti-mesothelin antibody with PTX-NPs. The phase transition of Ab-PTX-NPs was induced by low-power focused ultrasound, and its ultrasonography imaging was observed; laser scanning confocal microscopy and flow cytometry were used to detect the targeting ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells. The targeting and killing ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells was observed by in vitro targeting assay and apoptosis detection assay. The ovarian cancer model of BALB/c nude mice was constructed to observe the distribution of Ab-PTX-NPs in vivo as well as the effects on blood biochemistry and important organs of nude mice. Results:Ab-PTX-NPs were successfully prepared with a zeta potential of -(8.37±2.71) mV, a diameter of (690.46±28.75) nm, an encapsulation rate of (88.2±4.4)% for PTX, a drug loading capacity of (27.3±0.9)%, and a linkage rate of (94.9±2.8)% between anti-mesothelin antibody and PTX-NPs. Low-intensity focused ultrasound could successfully induce phase transition of Ab-PTX-NPs to realize ultrasonography imaging, and 6 W was the optimal excitation power for low-intensity focused ultrasound. Ab-PTX-NPs showed excellent targeting and killing ability to SKOV3 cells, and the apoptosis and necrosis rate of SKOV3 cells in the Ab-PTX-NPs group reached 79.6%. In vivo imaging showed that the fluorescence intensity at the tumor site of nude mice in the Ab-PTX-NPs group was significantly higher than that in the PTX-NPs group. Biosafety assay showed that 15 d after Ab-PTX-NPs administration, the serum aspartate aminotransferase, alanine aminotransferase, creatine kinase, low-density lipoprotein, blood creatinine, and urea nitrogen concentrations of nude mice were (174.163±20.596)U/L, (33.297±2.573)U/L, (1 959.978±72.212)U/L, (22.033±5.030)μmol/L, (0.393±0.058)mmol/L, and (26.405±4.957)mmol/L, which were not significantly different from those of the phosphate buffer solution (PBS) group, the NPs group, and the PTX-NPs group. The organs such as the heart, the liver, the spleen, the lungs and the kidneys remained intact, and what was seen by the naked eye and microscope was similar with those of the PBS group, NPs group and PTX-NPs group. Conclusion:Ab-PTX-NPs were successfully prepared, which had good ovarian cancer targeting ability and killing effect and effectively reduced the toxicity of PTX.

Objective To analyze the satisfaction of medical experience of outpatients in multi-campus of a large tertiary public hospital.Methods From January to March 2024,a questionnaire on outpatient satisfaction was sent to the outpatient department of Peking University First Hospital daily based on the Questionnaire Star platform to analyze the outpatient satisfaction rate and satisfaction score of medical services,and the influencing factors of outpatient satisfaction were explored by logistic regression analysis.Results Among the respondents,64.0％expressed high levels of satisfaction while 26.1％reported being relatively satisfied.Waiting time and consultation time play an important role.The diagnosis,treatment and health education and schedule of follow-up visits may affect the outpatient experience.Outpatient payment,outpatient environment,outpatient perceived complaints and timely resolution of dissatisfaction all could affect outpatient satisfaction.Conclusion The overall satisfaction of outpatients was high,and patient satisfaction of outpatient medical services in multi-campuses was consistent.On the premise of ensuring the quality of medical care,hospitals should actively carry out individualized health education,simplify the medical process,extend the outpatient service,and further improved the sense of gain of outpatients.

Currently, transcatheter intervention is the preferred treatment for patients with anatomically suitable atrial septal defects. However, the use of nickel-titanium alloy occluders in interventional procedures results in lifelong presence of the implant in the body, leading to complications such as metal allergies and arrhythmias in some patients. To overcome the short-term and long-term complications associated with the presence of metal, and to avoid radiation exposure and metal toxicity, this paper reports a case of successful transcatheter closure of atrial septal defect in a pediatric patient with metal allergies using fully biodegradable occluder under ultrasound guidance, achieving excellent results by interventional therapy.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.