There are numerous ethical dilemmas in families of children with kidney disease during the treatment stage. From the perspective of Giddens’ structured theory， this paper analyzed the ethical dilemmas， such as individual and family wealth disparity at the micro-level， doctor-patient information asymmetry and the attribution of medical decision-making rights at the meso-level， as well as unequal medical resources and an incomplete medical security system for children at the macro-level. The ethical dilemmas faced by families of children with kidney disease are the result of the structural constraint effect. The coping strategies they adopt in response to these dilemmas are the basis of structural reproduction and the products of the structural effect. As a group with subjective initiative， they are good at self-reflection. Through repeated cognitive evaluation， they can make a series of effective coping strategies to achieve their own goals， such as relying on family support and linking resources to seek social support， establishing online support groups and building an information sharing platform， assessing children’s best-interests judges and safeguarding their reasonable and legitimate rights and interests， planning and allocating high-quality medical resources and promoting the construction of the medical service system， as well as promoting the reform of the basic medical insurance system for children and improve the protection mechanism for major illnesses.

OBJECTIVE To provide practical basis and policy recommendations for improving the pharmacovigilance （PV） system construction in medical institutions across China. METHODS A questionnaire survey was conducted using a mixed sampling strategy of “online random sampling+offline supplementary sampling” to distribute questionnaires among pharmaceutical professionals in tertiary medical institutions nationwide. The questionnaire covered aspects such as the construction of PV systems， job position settings， information system support， operational practices， and multi-stakeholder collaboration. The data were analyzed using descriptive methods and SPSS 20.0 statistical software. RESULTS A total of 70 valid questionnaires were collected from 66 medical institutions， primarily Class A tertiary hospitals. The survey found that 90.00% had designated PV personnel and 74.29% routinely conducted PV activities. However， there were notable disparities in resource allocation and information system capacity， with less than 50% of the institutions conducting post-marketing drug re-evaluation. PV activities were primarily focused on the collection and reporting of adverse drug reactions， with limited capabilities in signal detection and risk assessment. CONCLUSIONS Among the surveyed tertiary hospitals， PV systems have begun to take shape. However， challenges persist in terms of system establishment， resource allocation， risk assessment， and inter-organizational coordination. Policy efforts should focus on strengthening regulatory frameworks， improving information sharing mechanisms， enhancing professional training， and strengthening collaboration between hospitals and market authorization holders to ensure the effective implementation of PV in medical institutions.

Objective: To investigate the trend in disease burden of interstitial lung disease (ILD) in China from 1990 to 2021, so as to provide a reference for formulating prevention and control strategies for chronic respiratory diseases. Methods: Based on the Global Burden of Disease 2021 database, data on the number of incident cases, incidence, standardized incidence, number of deaths, mortality, standardized mortality, number of disability-adjusted life years (DALY), DALY rate, and standardized DALY rate of ILD in China were collected. The incidence, mortality, and DALY rate were used to analyze the disease burden of ILD. The estimated annual percentage change (EAPC) was employed to assess the trend in standardized incidence, standardized mortality, and standardized DALY rate of ILD from 1990 to 2021. Rate decomposition analysis was applied to identify the main contributing factors affecting the trend in disease burden. Results: In 2021, China reported 48 514 cases, 7 674 deaths, and 222 288 person-years of DALY due to ILD, representing increases of 155.43%, 159.70%, and 97.34%, respectively, compared with 1990. From 1990 to 2021, the standardized incidence and standardized mortality of ILD in China showed upward trends (EAPC=1.106% and 0.239%, both P<0.05), while the standardized DALY rate showed a downward trend (EAPC=-0.230%, P<0.05). From 1990 to 2021, the standardized incidence and standardized mortality among males showed upward trends (EAPC=1.199% and 0.520%, both P<0.05), while the trend in the standardized DALY rate was not statistically significant (P>0.05). Among females, the standardized incidence of ILD showed an upward trend (EAPC=0.966%, P<0.05), while the standardized mortality and standardized DALY rate showed downward trends (EAPC=-0.306% and -0.760%, both P<0.05). In 2021, the incidence, mortality, and DALY rate of ILD in China increased with age, peaking in the group aged ≥95 years at 14.84/105, 13.90/105, and 124.71/105, respectively. Across all age groups aged ≥55 years, the incidence, mortality, and DALY rate of ILD were consistently higher in males than in females. The increase in the number of incident cases, deaths, and DALY due to ILD in China from 1990 to 2021 was primarily influenced by population aging, with contribution rates of 42.65%, 68.25%, and 69.79%, respectively. Conclusions From 1990 to 2021, the incidence and mortality risk of ILD in China showed upward trends, while the disability risk demonstrated a downward trend. Males bore a heavier disease burden of ILD, and aging was identified as the primary factor contributing to the increased burden of ILD in China.

Objective To investigate the diagnostic value of color Doppler ultrasound of neck vessels combined with head and neck CT angiography (CTA) in detecting carotid artery stenosis among patients with stroke. Methods A total of 104 patients with stroke admitted to the hospital between January 2023 and November 2024 were enrolled. All patients underwent color Doppler ultrasound of neck vessels and head and neck CTA, with digital subtraction angiography (DSA) used as the gold standard. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic performance of each modality alone and in combination for detecting carotid artery stenosis in patients with stroke. Results According to the DSA results, among the 104 patients, 7 were normal, while 47, 16, 25, and 9 cases showed mild, moderate, and severe stenosis and occlusion, respectively. Color Doppler ultrasound results showed 6 normal cases, and 45, 20, 23, and 10 cases of mild, moderate, and severe stenosis and occlusion, respectively. Using DSA as the gold standard, the sensitivity, specificity and kappa value for diagnosing carotid artery stenosis were 98.97%, 85.71% and 0.848, respectively. Head and neck CTA results showed 5 normal cases, and 47, 19, 22, and 9 cases of mild, moderate, and severe stenosis and occlusion, respectively. The sensitivity, specificity and kappa value of head and neck CTA for diagnosing carotid artery stenosis were 100.00%, 71.43% and 0.823, respectively. The combined examination results showed that among the 104 patients, there were 7 normal cases, and 46, 18, 24, and 9 cases of mild, moderate, and severe stenosis and occlusion, respectively. The sensitivity, specificity and kappa value of the combined diagnosis were 100.00%, 100.00% and 1.000, respectively. In the ROC analysis, the areas under the curves of color Doppler ultrasound, head and neck CTA, and the combined method were 0.968, 0.934, and 1.000, respectively, with no significant difference among the three ROC curves (Z = 1.017, 0.994, 1.527, respectively, P = 0.309, 0.320, 0.167, respectively). Conclusion Color Doppler ultrasound of neck vessels combined with head and neck CTA shows good consistency with DSA in diagnosing carotid artery stenosis and its severity among patients with stroke. This combined method demonstrates high diagnostic performance, making it worthy of clinical application and promotion.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism* ; Arthritis, Rheumatoid/immunology* ; Animals ; Dendritic Cells/metabolism* ; Paroxetine/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Lymphocyte Activation/drug effects* ; Female ; T-Lymphocytes/metabolism* ; Middle Aged

Breast cancer is the most common malignant tumor in women worldwide.HER2-positive and HER2-low breast cancers are highly aggressive subtypes with poor prognosis.First-line combination therapies targeting HER2 have significantly improved treatment outcomes for patients with advanced and metastatic breast cancer,but resistance inevitably develops.The emergence of antibody-drug conjugates(ADCs)brings new hope for the treatment of advanced HER2-positive and HER2-low breast cancers.This article analyzes the efficacy and safety of key ADC drugs,including adotrastuzumab emtansine(T-DM1),trastuzumab deruxtecan(DS-8201,T-DXd)and other drugs in the treatment of advanced HER2-positive and HER2-low breast cancers.It also reviews mechanisms of ADC resistance and discusses corres-ponding management strategies,aiming to provide more efficient and personalized treatment options for patients with advanced HER2-pos-itive and HER2-low breast cancers.

Objective To observe the value of artificial intelligence iterative reconstruction(AIIR)for reconstruction CT images of phantoms.Methods AIIR was developed through combining model-based iterative reconstruction(MBIR)with deep learning(DL)techniques.CT scanning of CCT MITA IQ phantom,CT ACR 464 phantom,Catphan 700 phantom,disc stack phantom and CT PBU-60 whole body phantom were performed,and the images were reconstructed with conventional algorithms like filtered back projection(FBP)and KARL 3D iterative reconstruction,as well as AIIR,respectively.Then the noise,X-ray dosage,as well as low contrast resolution,high contrast spatial resolution,cone-beam artifacts and streaking artifacts of various reconstructed images were compared.Results Compared to CT images reconstructed with conventional algorithms,those reconstructed with AIIR showed 61.74％—99.76％ reduction of image noise and 60.00％—90.00％ reduction of X-ray dosage,while increased image low contrast resolution to 1.99-4.86 times and high contrast spatial resolution to 1.55-2.57 times.Additionally,AIIR significantly reduced cone-beam artifacts and streaking artifacts.Conclusion AIIR showed obvious advantages for reconstruction CT images of phantoms compared with conventional algorithms.

Objective:To establish an element framework and template of broad informed consent applicable to clinical research,and to standardize the collection,storage,and reuse of medical data and biological samples,making them comply with ethical and legal requirements.Methods:A literature review and group discussion were employed to construct the draft of the element framework and template of broad informed consent form.The Delphi expert consultation method was used to conduct two rounds of correspondence with 13 experts in relevant fields to determine the two-level element framework and template of broad informed consent form.Results:The response rates for the two rounds of expert consultation questionnaires were above 90%,the experts'positive coefficients were good,and the coefficients of authority(Cr)were higher than 0.85.In the second round of consultation,the average importance value was≥4.4,the coefficient of variation(CV)was<0.17,and Kendall's W was 0.184(P<0.001),indicating that the expert opinions tended to be consistent.Ultimately,an element framework and template of broad informed consent form was established,consisting of 4 first-level items and 21 second-level items.Conclusion:The constructed element framework and template of broad informed consent form is highly scientific and applicable,providing references for clinical research.