ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 （C6） was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction， resulting in two types of micelles： Tfn/PCL_H and Tfn/PCL_L. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively， and the efficiency of the two methods， along with the purity of the final micelles， was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm， and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCL_L and Tfn/PCL_H， respectively. The micelle population was monodisperse. The purification results showed that， for the ultrafiltration method， after two and one rounds of purification， the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCL_H and Tfn/PCL_L， respectively. For the dextran gel filtration method， the Tfn/C6 ratio reached 23.7 for the Tfn/PCL_H group after two rounds of purification. However， for the Tfn/PCL_L group， the Tfn/C6 ratio increased during four rounds of dextran gel purification， and a significant difference （P = 0.042 4） was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method， the Tfn density of Tfn/PCL_H and Tfn/PCL_L were 94.9% and 13.8%， respectively. For the dextran gel filtration method， the density of the two micelles were 95.6% and 14.4%， respectively. For Tfn/PCL_L group， the density results revealing a statistically significant difference （P=0.000 2）. ConclusionThe purification efficiency of the two methods is comparable. However， the purity of the final micelles shows a significant difference， with the dextran gel filtration method resulting in higher purity， particularly for the Tfn/PCL_L micelles.

Objective To investigate the effect of subanesthetic dose of esketamine on emergence agitation(EA)in patients undergoing laparoscopic hernia repair.Methods Seventy-two male patients who treated with lapa-roscopic hernia repair under general anesthesia were randomly divided into AS group(subanesthetic esketamine)and control group.In the AS group,0.2 mg/kg of esketamine was administered intravenously 30 minutes before the surgery ended,while the control group was given an equal volume of normal saline.Upon surgery completion,patients were transferred to PACU with endotracheal tube retained,and the time to extubation was recorded.Hemo-dynamic parameters were measured immediately after extubation and at 10 min,30 min,1 h,and 4 h thereafter.Patients' pain and sedation levels were assessed at the above time points using RASS and VAS,respectively.The incidence of EA was evaluated using the Confusion Assessment Method for the Intensive Care Unit(CAM-ICU).Observation duration in the PACU and recovery outcomes within 24 hours postoperatively were assessed via the QoR-40 and adverse events were recorded.Results Compared to those in the control group,patients in the AS group had higher HR and MAP at 10 min post-extubation,and the changes in HR and MAP over time were more stable(P<0.05).The RASS and VAS scores in the AS group were significantly lower than those in the control group at the time of extubation and all subsequent time points(P<0.05),both groups showed temporal changes in RASS and VAS scores(P<0.05),but the change process in the AS group was more stable(P<0.05).Postoperative extubation time,PACU observation duration,and adverse event rates(delirium,respiratory depression,nausea and vomiting)did not differ significantly between the two groups(P>0.05),while recovery quality was markedly better in the AS group(P<0.05).Conclusion Subanesthetic esketamine effectively alleviates pain and the incidence of EA,supports hemodynamic stability during PACU stay,and enhances recovery quality in patients undergoing laparo-scopic hernia repair,demonstrating clinical value.

OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin(IMP)on doxorubicin(DOX)resistance in breast cancer.METHODS The effects of maximum non-toxic concentration(100 μg/mL)of IMP combined with different concentrations of DOX(12.5,25,50,75,100 μg/mL)on the proliferation of MCF-7/DOX cells were determined by MTT method.MCF-7/DOX cells were divided into blank control group(1‰ dimethyl sulfoxide),DOX group(50 μg/mL),IMP+DOX group(100 μg/mL IMP+50 μg/mL DOX)and IMP group(100 μg/mL).mRNA and protein expressions of multidrug resistance protein 1(MDR1)and multidrug resistance-associated protein l in each group were measured.The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology,along with gene ontology(GO)enrichment analyses and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.RESULTS Compared with DOX alone,the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL,the reverse fold was 1.90,and the mRNA expression of MDR1 was significantly down-regulated(P＜0.05).The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification,multiple biological processes,and cell killing.The main pathway involved was the p53 signaling pathway,and the key targets mainly included constitutively photomorphogenic protein 1(COP1),cyclin E1(CCNE1),growth arrest and DNA damage-inducible protein 45A(GADD45A)and GADD45B.The results of the verification experiments showed that compared with DOX group,there was a trend of up-regulation of COP1 mRNA,and significant down-regulation of CCNE1,GADD45A,and GADD45B mRNA expression in IMP+DOX group(P＜0.05).CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1,CCNE1,GADD45A and GADD45B targets in the p53 signaling pathway.

Objective To explore the application value of iterative model reconstruction(IMR)technique in low-dose lumbar CT scanning.Methods A total of 48 patients who underwent lumbar CT plain scan were selected and divided into regular-dose group(group A)and ultra-low dose group(group B).The group A underwent imaging with 120 kV tube voltage,automatic tube current modulation technology,and iDose 4 reconstruction.The group B was scanned with a tube voltage of 100 kV and a tube current of 80 mAs,and the images of B1 and B2 groups were reconstructed by iDose 4 and IMR,respectively.The standard deviation(SD)value(the SD value represents the noise of the measured tissue),signal-to-noise ratio(SNR),and contrast-to-noise ratio(CNR)of cancellous bone,intervertebral disc,dural sac,and psoas muscle were measured and calculated at the L3-L4 vertebral body level.Two diagnosticians rated the image quality.Sample t-test and ANOVA were used to compare the measurement results and subjective scores.Results The comparison of SD for intervertebral disc,dural sac,and psoas muscle showed group B2＜group A＜group B1,while the subjective score comparison indicated group A＞group B2＞group B1.The SNR for intervertebral disc and psoas muscle demonstrated group B2＞group A＞group B1.There was no significant difference in bone quality score between group A and group B1(P＞0.05),but there was a significantly different between the bone quality scores of group B2 and those obtained with iDose 4 reconstruction(group A and group B1)(P＜0.05).The effective dose(ED)of group B was reduced by approximately 70.28％compared with group A.Conclusion IMR can significantly reduce SD,improves SNR and CNR,resulting in high-quality images.Compared to iDose 4 technique,IMR has more advantages in soft tissue display,while iDose 4 technique is superior in observing fine bone structures.The combined application of iDose 4 and IMR technique ensures high-quality images for diagnosis,while significantly reducing the radiation dose to patients.

The neuropsychiatric disorder course is among the most challenging subjects in medical education, currently facing the "three difficulties" of teaching, learning, and transition from theory to practice. This study attempts to carry out clinical thinking informatization technology-based teaching reform guided by clinical competence. A cognitive map for neuropsychiatric disorders was developed using a symptom-based framework. Leveraging this cognitive map and integrating artificial intelligence, a clinical thinking teaching application for neuropsychiatric disorders was designed and continuously refined. Reform initiatives were explored and summarized in areas such as theoretical teaching, practical teaching, standardized training for resident physicians, teaching assessment, and textbook reform. The reform improved the clinical thinking and clinical competence of students for neuropsychiatric disorders.

Objective To evaluate the safety and efficacy of enteroscopy in the treatment of rare small intestinal diseases,including Peutz-Jeghers syndrome(PJS),blue rubber bleb nevus syndrome(BRBNS),and cryptogenic multifocal ulcerative stenosing enteritis(CMUSE),thereby providing a reference for clinical diagnosis and treatment.Methods Patients with rare small intestinal diseases diagnosed and treated in the De-partment of Gastroenterology,Shanghai Changhai Hospital,from January 2020 to December 2024 were included.Detailed records of patients' general information,clinical manifestations,auxiliary examinations,and endoscopic treatment data were collected and systematically analyzed.Results A total of 30 PJS patients un-derwent 88 small intestinalpolypectomies under enteroscopy,including 62 procedures via the oral approach(mean operative time:92.8±30.1 min;largest polyp diameter:2.9±1.2 cm)and 26 via the anal approach(95.0±29.4 min;1.9±1.3 cm).Six adverse events occurred in the oral approach group.Ten BRBNS patients received 26 endoscopic treatments(25 sclerosing agent injection under enteroscopy and 1 sclerosing agent injec-tion combined with ligation session),with a mean operative time of 68.1±17.4 min.Eleven intestinal venous aneurysms were ligated,and 4 adverse events were reported.Five CMUSE patients underwent 6 endoscopic treatments(5 samll intestinal stenosis balloon dilations and 1 samll intestinal stenosis incision),with no ad-verse events observed.Conclusions Small intestinal endoscopy is feasible,safe,and effective for treating rare small intestinal diseases such as PJS,BRBNS,and CMUSE.For PJS patients,the oral approach should be pri-oritized.Sclerosing agent injection under enteroscopy for intestinal venous aneurysms in BRBNS via small bowel endoscopy is safe and effective,though the safety of ligation of venous aneurysms under enteroscopy requires further investigation.Stenosis balloon dilation and incision under enteroscopy are both feasible options for CMUSE,and these two approaches can complement each other.

Objective To evaluate the safety and efficacy of enteroscopy in the treatment of rare small intestinal diseases,including Peutz-Jeghers syndrome(PJS),blue rubber bleb nevus syndrome(BRBNS),and cryptogenic multifocal ulcerative stenosing enteritis(CMUSE),thereby providing a reference for clinical diagnosis and treatment.Methods Patients with rare small intestinal diseases diagnosed and treated in the De-partment of Gastroenterology,Shanghai Changhai Hospital,from January 2020 to December 2024 were included.Detailed records of patients' general information,clinical manifestations,auxiliary examinations,and endoscopic treatment data were collected and systematically analyzed.Results A total of 30 PJS patients un-derwent 88 small intestinalpolypectomies under enteroscopy,including 62 procedures via the oral approach(mean operative time:92.8±30.1 min;largest polyp diameter:2.9±1.2 cm)and 26 via the anal approach(95.0±29.4 min;1.9±1.3 cm).Six adverse events occurred in the oral approach group.Ten BRBNS patients received 26 endoscopic treatments(25 sclerosing agent injection under enteroscopy and 1 sclerosing agent injec-tion combined with ligation session),with a mean operative time of 68.1±17.4 min.Eleven intestinal venous aneurysms were ligated,and 4 adverse events were reported.Five CMUSE patients underwent 6 endoscopic treatments(5 samll intestinal stenosis balloon dilations and 1 samll intestinal stenosis incision),with no ad-verse events observed.Conclusions Small intestinal endoscopy is feasible,safe,and effective for treating rare small intestinal diseases such as PJS,BRBNS,and CMUSE.For PJS patients,the oral approach should be pri-oritized.Sclerosing agent injection under enteroscopy for intestinal venous aneurysms in BRBNS via small bowel endoscopy is safe and effective,though the safety of ligation of venous aneurysms under enteroscopy requires further investigation.Stenosis balloon dilation and incision under enteroscopy are both feasible options for CMUSE,and these two approaches can complement each other.

Objective To investigate the effect of subanesthetic dose of esketamine on emergence agitation(EA)in patients undergoing laparoscopic hernia repair.Methods Seventy-two male patients who treated with lapa-roscopic hernia repair under general anesthesia were randomly divided into AS group(subanesthetic esketamine)and control group.In the AS group,0.2 mg/kg of esketamine was administered intravenously 30 minutes before the surgery ended,while the control group was given an equal volume of normal saline.Upon surgery completion,patients were transferred to PACU with endotracheal tube retained,and the time to extubation was recorded.Hemo-dynamic parameters were measured immediately after extubation and at 10 min,30 min,1 h,and 4 h thereafter.Patients' pain and sedation levels were assessed at the above time points using RASS and VAS,respectively.The incidence of EA was evaluated using the Confusion Assessment Method for the Intensive Care Unit(CAM-ICU).Observation duration in the PACU and recovery outcomes within 24 hours postoperatively were assessed via the QoR-40 and adverse events were recorded.Results Compared to those in the control group,patients in the AS group had higher HR and MAP at 10 min post-extubation,and the changes in HR and MAP over time were more stable(P<0.05).The RASS and VAS scores in the AS group were significantly lower than those in the control group at the time of extubation and all subsequent time points(P<0.05),both groups showed temporal changes in RASS and VAS scores(P<0.05),but the change process in the AS group was more stable(P<0.05).Postoperative extubation time,PACU observation duration,and adverse event rates(delirium,respiratory depression,nausea and vomiting)did not differ significantly between the two groups(P>0.05),while recovery quality was markedly better in the AS group(P<0.05).Conclusion Subanesthetic esketamine effectively alleviates pain and the incidence of EA,supports hemodynamic stability during PACU stay,and enhances recovery quality in patients undergoing laparo-scopic hernia repair,demonstrating clinical value.

Paradoxical psoriasis is a special adverse drug reaction characterized by the new onset, exacerbation, or phenotypic change of psoriatic lesions during treatment with biological agents. In recent years, with the increasing use of biologics, this condition has garnered growing attention from clinicians. The pathogenesis of paradoxical psoriasis is complex and its clinical manifestations are highly heterogeneous. Diagnosis currently relies primarily on clinical features and medication history due to the lack of unified diagnostic criteria. Furthermore, treatment strategies—such as whether to discontinue the original biologic agent or switch therapies—remain controversial, posing significant challenges in clinical management.This article presents a case of paradoxical psoriasis occurring in a patient with ankylosing spondylitis following treatment with the tumor necrosis factor-α inhibitor (TNFi) infliximab. By discussing the clinical characteristics of this case, we aim to enhance clinicians' understanding of this condition, reduce misdiagnosis and underdiagnosis, and provide valuable insights for its diagnosis and treatment.

Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.