Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Fractional flow reserve (FFR), an established modality for functionally assessing coronary artery disease, is increasingly applied to diagnose and manage lower extremity arterial disease. By incorporating functional parameters, FFR enhances revascularization precision by quantifying the hemodynamic impact of stenotic lesions, thereby overcoming limitations of conventional imaging. Key clinical applications in lower extremity disease include functional assessment in moderate intermittent claudication, post-vascular preparation strategy optimization, and predicting revascularization outcomes and complications. Advances in pressure wire and microcatheter systems, alongside non-invasive imaging-derived FFR techniques, are improving its feasibility and applicability. However, widespread adoption is challenged by the complex anatomy of the lower extremity arterial system, frequent severe calcification and diffuse disease, and a current lack of standardized FFR cutoff values. Promoting the standardized use of FFR is crucial for shifting the clinical management paradigm from anatomy-based repair toward functional reconstruction.
Humans ; Lower Extremity/blood supply* ; Peripheral Arterial Disease/diagnosis* ; Fractional Flow Reserve, Myocardial ; Endovascular Procedures/methods* ; Intermittent Claudication/physiopathology*

This study was aimed at exploring the interaction between the nucleoprotein(NP)of influenza A virus(IAV)and TRIM25.The physicochemical properties and protein structure of IAV NP protein were analyzed through bioinformatics methods.The interaction between IAV NP and TRIM25 proteins was simulated with molecular docking techniques,and the in-teraction sites were predicted.With the cDNA of the A/Puerto Rico/8/1934(H1N1)PR8 strain as the template,the NP pro-tein was cloned into the eukaryotic expression vector pCMV-C-Flag through PCR amplification,the eukaryotic expression re-combinant plasmid pCMV-Flag-NP was constructed,and the expression was further verified.The protein expression levels of pCMV-Flag-NP and pCMV-HA-TRIM25 were detected at various time periods.The interaction between NP protein and TRIM25 protein was verified by co-immunoprecipitation.The co-localization of NP protein and TRIM25 protein in cells was ob-served with laser confocal microscopy.Bioinformatics analysis revealed that the NP protein consists of 498 amino acids and 20 amino acids,and is an unstable hydrophilic protein.The NP protein has multiple phosphorylation sites,as well as N-glycosyla-tion and O-glycosylation sites,but no transmembrane domain or signal peptide domain.Additionally,the NP protein's second-ary structure consists of a high proportion of alpha-helices and random coils.The molecular docking prediction results indicated that IAV NP interacts with TRIM25 protein and has multiple potential interaction sites,including the 233rd alanine,234th ala-nine,236th lysine,and 440th alanine of the NP protein.After successfully constructing and expressing the IAV NP protein,we verified the interaction between IAV NP and TRIM25 protein by immunoprecipitation and laser confocal microscopy obser-vations.Our results together suggested that the structure of the IAV NP protein is closely related to its function,and its im-portance to the virus is clear.In addition,the interaction between IAV NP and TRIM25 protein may be associated with TRIM25's anti-influenza virus mechanism.Further in-depth research may provide new ideas for anti-influenza virus strategies.

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

Objective To design a practice courses and competency-oriented training in rehabilitation psychology,in response to the demands of team-based and interprofessional practices for professionals,based on World Health Organization re-habilitation competency framework(RCF).Methods Using the five core domains of RCF(practice,professionalism,learning and development,management and leadership,and research),this study analyzed the competencies and role positioning of undergraduate rehabilita-tion psychology students within team-based and interprofessional rehabilitation settings.It identifies the core competencies needed in these contexts and corresponding practical teaching approaches,to enhance students'ability to translate disciplinary knowledge into team-based and interprofessional practice competencies in real-world rehabilitation scenarios.Results The study yielded a competency-oriented practical curriculum structured around the teamwork and interprofes-sional practice requirements for rehabilitation psychology professionals.Based on RCF,we defined specific core competencies and developed a curricular framework incorporating pedagogical methods such as integrated as-sessments based on International Classification of Functioning,Disability and Health,motivational interviewing,case study analysis,and standardized patient simulations.These methods are designed to build student proficien-cy in team communication,collaborative decision-making,case management and evidence-based practice.Conclusion In undergraduate rehabilitation psychology education,developing competency-based practical courses tar-geting team-based and interprofessional service competencies,which grounded in RCF,can enhance the quality and efficiency of talent cultivation in the field.It also helps improve students'capabilities in collaborative and in-terprofessional practice.RCF provides a theoretical foundation,practical tools,and reference frameworks for building competency-oriented curricula and instructional methods in rehabilitation psychology.

Objective To propose an in vitro cytotoxicity evaluation method for novel iron-based biodegradable mateirals focusing on their degrading characteristics.Methods Half-finished scaffolds of nitrided iron tubes with a higher iron content of over 99％and a nitrogen content of 0.03％to 0.20％were selected as test samples,and based on the treatment mode were divided into an anaerobic treatment group,a non-anaerobic treatment group,a non-anaerobic treatment with removed iron particle group and a non-anaerobic treatment with plate-washing group.The anaerobic treatment group was processed in an anaerobic workstation;the conventional treatment group underwent standard handling in a biosafety cabinet;the conventional treatment with removed iron particle group was subjected to iron particle elimination using a Midimacs Starting Kit manual sorter after conventional treatment;and the conventional treatment with plate-washing group was rinsed with 0.9％sodium chloride injection before tetrazolium salt reagent treatment.Different extraction media(simulated body fluid,cell culture medium,phosphate buffer and 0.9％sodium chloride injection)were used for the immersion treatment of the test samples in each group to compare the effects of the degradation products on the survival rate of L929 cells.Results The anaerobic treatment group and the conventional treatment with removed iron particle group exhibited no detectable cytotoxicity.Trypan blue staining revealed significant cytotoxicity in the conventional treatment group,while false-negative results emerged due to interactions between the tetrazolium salt reagent and degradation products.In the non-anaerobic treatment with washing plate group,the false negative from iron particles was eliminated while potential cytotoxicity was showen,and the result accuracy was affected because some cells were washed out.Conclusion The proposed method can be used for the in vitro cytotoxicity evaluation,and facilitates the safety evaluation of the application of such materials.[Chinese Medical Equipment Journal,2025,46(3):35-41]

Objective To propose an in vitro cytotoxicity evaluation method for novel iron-based biodegradable mateirals focusing on their degrading characteristics.Methods Half-finished scaffolds of nitrided iron tubes with a higher iron content of over 99％and a nitrogen content of 0.03％to 0.20％were selected as test samples,and based on the treatment mode were divided into an anaerobic treatment group,a non-anaerobic treatment group,a non-anaerobic treatment with removed iron particle group and a non-anaerobic treatment with plate-washing group.The anaerobic treatment group was processed in an anaerobic workstation;the conventional treatment group underwent standard handling in a biosafety cabinet;the conventional treatment with removed iron particle group was subjected to iron particle elimination using a Midimacs Starting Kit manual sorter after conventional treatment;and the conventional treatment with plate-washing group was rinsed with 0.9％sodium chloride injection before tetrazolium salt reagent treatment.Different extraction media(simulated body fluid,cell culture medium,phosphate buffer and 0.9％sodium chloride injection)were used for the immersion treatment of the test samples in each group to compare the effects of the degradation products on the survival rate of L929 cells.Results The anaerobic treatment group and the conventional treatment with removed iron particle group exhibited no detectable cytotoxicity.Trypan blue staining revealed significant cytotoxicity in the conventional treatment group,while false-negative results emerged due to interactions between the tetrazolium salt reagent and degradation products.In the non-anaerobic treatment with washing plate group,the false negative from iron particles was eliminated while potential cytotoxicity was showen,and the result accuracy was affected because some cells were washed out.Conclusion The proposed method can be used for the in vitro cytotoxicity evaluation,and facilitates the safety evaluation of the application of such materials.[Chinese Medical Equipment Journal,2025,46(3):35-41]