The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

Medical artificial intelligence （AI） is a new type of application formed by the combination of machine learning， computer vision， natural language processing， and other technologies with clinical medical treatment. With the continuous iteration and development of relevant technologies， medical AI has shown great potential in improving the efficiency of diagnosis and treatment， and service quality， but it also increases the possibility of triggering ethical issues. Ethical issues resulting from the clinical application of medical AI were analyzed， including the lack of algorithmic interpretability and transparency of medical AI， leading to information asymmetry and cognitive discrepancies； the concerning status of security and privacy protection of medical data； and the complex and unclear division of responsibilities due to the collaborative participation of multiple subjects in the clinical application of medical AI， resulting in increased difficulty in the identification of medical accidents and clarification of responsibilities. The paper proposed the principles of not harming patients’ interests， physician’s subjectivity， fairness and inclusiveness， and rapid response. It also explored the strategies and implementation paths for responding to the ethical issues of medical AI from multiple perspectives， including standardizing the environment and processes， clarifying responsibility attribution， continuously assessing the impact of data protection， guaranteeing data security， ensuring model transparency and interpretability， carrying out multi-subject collaboration， as well as the principles of being driven by ethical values and adhering to the “human health-centeredness.” It aimed to provide guidance for the healthy development of medical AI， ensuring technological progress while effectively managing and mitigating accompanying ethical risks， thereby promoting the benign development of medical AI technology and better serving the healthcare industry and patients.

Objective:To investigate the effect of Isoorientin(Iso)on development of oral squamous cell carcinoma(OSCC)and the regulation on immune response mediated by cGAS-STING signaling pathway.Methods:CAL 27 cells were divided into control group,low,medium and high concentration Iso groups and high concentration Iso+cGAS inhibitor group(high concentration Iso+RU.521 group).Proliferation activity of CAL 27 cells was detected by MTT;TUNEL method was applied to detect apoptosis of CAL 27 cells;Transwell chamber test was applied to detect migration and invasion of CAL 27 cells;Western blot was applied to detect expressions of cGAS-STING pathway related proteins in CAL 27 cells;the tumor transplantation model of mice was prepared,and the tumor inhibi-tion rate was calculated.At the same time,peripheral blood was taken to detect the differentiation of T lymphocyte subsets in peripheral blood of mice in each group by flow cytometry.Results:Compared with control group,proliferation activity,numbers of migration and invasive cells in Iso treated groups were decreased,apoptosis rate,expressions of cGAS,STING protein,and phosphorylation expres-sions of TBK1,IRF3,tumor inhibition rate of mice,and percentages of CD4+T,CD8+T cells in peripheral blood were increased(P<0.05);further use of cGAS inhibitors reversed the inhibitory effect of Iso on development of OSCC and the promotion on cGAS-STING signaling pathway(P<0.05).Conclusion:Iso can inhibit the development of OSCC by activating the immune response mediated by cGAS-STING signaling pathway.

Objective:This study analyzes the clinicopathological features and prognostic factors of early-stage gastric mixed adenoneuroendocrine carcinoma (G-MANEC), which is an exceedingly rare malignancy, in an effort to provide evidence-based insights for clinical decision-making.Methods:A retrospective observational study was conducted using the clinical data of 36 patients with early-stage G-MANEC who underwent surgical resection at Zhongshan Hospital, Fudan University, from July 2014 to May 2022. The observed indicators included clinicopathological data and follow-up information on recurrence, metastasis, and overall survival (OS).Results:Among the 36 patients there were 21 males and 15 females, aged 32-84 (65±11) years. The most common initial symptoms were abdominal pain and distension (19/36, 52.8%), followed by incidental findings during physical examinations (7/36, 19.4%). Tumors were located in the proximal stomach in 13 cases (36.1%), the middle stomach in 4 cases (11.1%), and the distal stomach in 19 cases (52.8%). Average tumor diameter was (2.48±1.18) cm. Gross morphology included elevated type in 12 cases (33.3%), flat type in 20 cases (55.6%), and depressed type in 4 cases (11.1%). Ulceration was present in 12 cases (33.3%). There were 11 cases (30.6%) at T1a stage and 25 cases (69.4%) at T1b stage. Lymph node metastasis was positive in 10 cases (27.8%), and the differentiation grades of the adenocarcinoma component were Grade I, II, and III in 3 (8.3%), 10 (27.8%), and 23 (63.9%) cases, respectively. Furthermore, the proportion of neuroendocrine carcinoma component was ≥50% in 18 cases (50.0%) and <50% in 18 cases (50.0%). Lymphovascular or perineural invasion was present in 18 cases (50.0%). Lauren classification included mixed type in 10 cases (27.8%), intestinal type in 19 cases (52.8%), and diffuse type in 7 cases (19.4%), and chromogranin A (CgA) positivity was found in 20 cases (55.6%). Additionally, the Ki-67 index positivity was found in 26 cases (72.2%). Total gastrectomy was performed in 12 cases (33.3%) and partial gastrectomy in 24 cases (66.7%), with a median follow-up duration of 77.5 months. The 3-year and 5-year OS rates were 88.89% and 79.67%, respectively. Univariate analysis revealed that age, gross morphology, ulceration, proportion of neuroendocrine carcinoma component, lymphovascular or perineural invasion, and chromogranin A (CgA) positivity showed statistical significance in their association with OS ( P<0.10). Multivariate Cox regression analysis further identified ulceration (HR=7.74, 95%CI: 1.24-48.30, P=0.028) and CgA positivity (HR=21.76, 95%CI: 1.86-53.97, P=0.014) as independent risk factors of OS. Conclusions:Patients with early-stage G-MANEC are typically asymptomatic, and those with ulceration or positive CgA immunohistochemical staining tend to have a poor prognosis.

Objective:To investigate clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) complicated with asthma.Methods:A self-controlled study before and after treatment was conducted to retrospectively analyze 45 patients with moderate to severe atopic dermatitis combined with asthma who received dupilumab in the respiratory allergy clinic of North Theater Command General Hospital from January 2021 to May 2024, which age ≥12 years, including 27 males, 18 females. The treatment period was 4 to 12 months. All patients were treated with dupilumab combined with inhaled glucocorticoids and long-acting beta2-receptor agonists, as well as symptomatic drugs for atopic dermatitis. Analyze the clinical data of the patients before and after treatment, including lung function, asthma and AD-related assessment scales. Generalized estimation equation was used to analyze the simple effect of time on the repeated measurement data following non-normal distribution, and Wilcoxon signed rank test was used to compare the differences of each observation index before and after treatment.Results:Among 45 patients with moderate to severe atopic dermatitis complicated with asthma, after treatment with dupilumab, the FEV 1 increased from 2.39 (1.87, 2.83) L at baseline to 2.50 (1.84, 2.97) L 3 months after treatment ( Z=2.417, P=0.016), 2.60 (1.95, 3.14) L 6 months after treatment ( Z=2.896, P=0.004); the FEV 1pred% increased from 74.10% (67.70%, 78.75%) at baseline to 77.09% (68.40%, 80.24%) at 3 months after treatment ( Z=2.574, P=0.010), and 77.20% (71.10%, 80.72%) at 6 months after treatment ( Z=2.861, P=0.004). Meanwhile, there were statistically significant differences in the ACT and Mini-AQLQ scales at 3, 6, and 12 months after treatment compared with those before treatment (ACT score Z=3.170, 4.216, 5.723; Mini-AQLQ score Z=3.231, 4.133, 5.826; all P<0.05). The EASI scale decreased from baseline 25.90 (18.95, 33.45) to 6.20 (1.15, 8.35) at 4 months after treatment ( Z=5.842, P<0.05) and 4.90 (2.75, 8.35) at 6 months after treatment ( Z=5.841, P<0.05), 4.00 (3.15, 5.05) at 12 months after treatment ( Z=5.841, P<0.05); The scores of each scale of IGA, NRS and DLQI decreased significantly compared with the baseline after 4 months, 6 months and 12 months of treatment, and this trend became more obvious with the extension of treatment time. The differences were statistically significant (IGA score Z=6.247, 6.070, 5.946; NRS score Z=5.960, 5.893, 5.879; DLQI score Z=5.880, 5.850, 5.848; all P<0.05). During treatment, 1 patient had local adverse reactions at the injection site and 1 patient had conjunctivitis. Conclusion:Dupilumab may have a positive effect on improving the clinical efficacy of patients with moderate to severe atopic dermatitis complicated with asthma. During the 12-month observation period, this biological agent generally demonstrated good safety characteristics.

Objective:To investigate, for multi-sensitized allergic rhinitis (AR) patients allergic to dust mites combined with other allergens (pollen, mold, animal dander, etc.), whether the single dust mite subcutaneous immunotherapy (SCIT) can improve the specific symptoms caused by other allergens in the patients, and to analyze the relationship between the effectiveness of symptom improvement in these patients and the type, quantity and severity of the allergens.Methods:A multicenter retrospective study was conducted to collect mul-sensitized AR patients from allergy or respiratory departments of 5 hospitals who received house dust mite allergen preparation SCIT for 12 to 36 months and met other inclusion and exclusion criteria from February to July 2024. General clinical data were collected and the perennial or seasonal symptoms before and after treatment were evaluated with visual analogue scale (VAS) to assess whether there was an perennial or allergen-specific symptom improvement (VAS score decrease ≥30%), by which the patients were divided into effective group and ineffective. R software was used to analyze the differences between groups by using Fisher′s exact test and Mann-Whitney U test. Results:A total of 62 patients were enrolled, and the treatment were effective in 39 of them, with an effective rate of 62.9%. For allergen-specific symptoms, the median age of the effective group was higher than that of the ineffective group (12 years old vs. 8 years old, P=0.039), and the effective rate in dust mite specific immunoglobin E (sIgE) grade ≤5 group was higher than that in sIgE grade >5 group (81.6% vs. 45.5%, P=0.008), and the effective rate of mold sIgE grade ≤2 group was higher than that of sIgE grade >2 group (83.3% vs. 28.6%, P=0.045), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). For perennial symptoms, the effective rate in the mold grade ≤2 group was higher than that in the sIgE grade >2 group (91.3% vs. 28.6%, P=0.010), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). There was no significant correlation between the treatment effectiveness of perennial or allergen-specific symptoms and the number of combined allergens, the grade of skin test, and the difference between the grade of combined allergens and that of dust mites ( P>0.05). Conclusion:Among the patients with multi-sensitized AR allergic to dust mites included in this study, single dust mite SCIT is effective in some of them, and for allergen-specific symptoms, the effective group was elder, and dust mite sIgE grade 6 and mold sIgE grade ≥2 was related to the low effective rate of SCIT. The present results are insufficient for selecting single or multiple AIT in any type of multi-sensitized patients.

OBJECTIVE To investigate the effect and underlying mechanism of hydroxytyrosol(HT)on mouse chondrocyte injury induced by oxidative stress.METHODS Mouse chondrocytes were incubated with varying concentrations of HT 0-400 μmol L-1 for 24 h,and the viability of the mouse chondrocytes was assessed using CCK-8 kit.An oxidative stress model of chondrocytes was estab-lished by the addition of H2O2 200 μmol L-1.The experimental groups included the cell control group,H2O2 group,and H2O2+HT 10,50 and 250 μmol·L-1 groups.After 24 h,the mRNA expression levels of interleukin-6(IL-6),cyclooxygenase-2(COX-2),prostaglandin E2(PGE2),inducible nitric oxide synthase(iNOS),matrix metalloproteinase-3(MMP-3),MMP-13,a disintegrin and metalloproteinase with throm-bospondin motifs-4(ADAMTS-4),ADAMTS-5,SRY-box transcription factor-9(SOX-9)and aggrecan(ACAN)in mouse chondrocytes were detected by real-time quantitative PCR,the intracellular reactive oxygen species(ROS)level in chondrocytes was measured with 2,7-dichlorodihydrofluorescein diace-tate(DCFH-DA)staining,while the mitochondrial membrane potential was evaluated using JC-1 staining.After 48 h,the protein expression levels of iNOS,COX-2,MMP-13,and type Ⅱ collagen(Col-2)in mouse chondrocytes were detected using Western blotting.RESULTS HT at concentrations≤350 μmol·L-1 had no significant effect on the survival of mouse chondrocytes.Compared with the cell control group,after 24 h,the mRNA expression levels of IL-6,COX-2,PGE2,iNOS,MMP-3,MMP-13,ADAMTS-4 and ADAMTS-5 in the chondrocytes of mice in the H2O2 group were increased,while the mRNA expression levels of SOX-9 and ACAN were decreased.Additionally,there was an elevation in the ROS level and a significant loss of mitochondrial membrane potential in the chondrocytes of mice.Compared with the H2O2 group,after treatment with HT 10,50 and 250 μmol·L-1,there were significant decreases in mRNA expression levels of IL-6,COX-2,PGE2,iNOS,MM P-3,MMP-13,ADAMTS-4 and ADAMTS-5,the mRNA expressions of SOX-9 and ACAN were increased,the ROS level was lowered.After treatment with HT 50 and 250 μmol L-1,the loss of mitochondrial membrane potential was ameliorated.Compared to the cell control group,the protein expressions of iNOS,COX-2 and MMP-13 were upregulated in the H2O2 group,while the protein expression of Col-2 was downregulated after 48 h.Compared to the H2O2 group,treatment with HT at concentrations of 10,50 and 250 μmol·L-1 resulted in decreased protein expressions of iNOS,COX-2 and MMP-13 in mouse chondrocytes,but the protein expression of Col-2 increased following treatment with HT 50 and 250 μmol L-1.CONCLUSION HT can ameliorate H2O2-induced chondrocyte injury by reducing intracellular ROS levels and alleviating the loss of mitochondrial membrane potential,suppressing the release of inflammatory cytokines,inhibiting catabolic processes,and promoting anabolic activities.

Objective To explore the characteristics,potential challenges,and optimization paths of high-quality development policies for public hospitals in China,and to provide reference for policy formulation and implementation.Methods The 31 policy documents on high-quality development of public hospitals issued at the central and provincial levels between 2021 and 2024 were coded using Nvivo 11 software,and a three-dimensional analytical framework was constructed on the basis of the policy tools,stakeholders,and system dimensions,combining both quantitative and qualitative methods for content analysis.Results It found that the distribution of policy content in the three dimensions was characterized by stage imbalance:policy tools were mainly environmental,followed by supply,and demand;stakeholder attention was focused on public hospitals and healthcare administrations,and patient attention was low;The system dimension focused mainly on the macro level,with less distribution at the meso and micro levels.Although the unbalanced distribution of policy instruments is relevant at certain stages,the long-term structural imbalance may lead to insufficient systemic policies and weakened stakeholder synergies,and there is an urgent need to optimize the structure of instruments.Conclusions It is recommended to increase the proportion of demand-based policy instruments in policy design and dynamically adjust the synergistic application of the three types of instruments;to strengthen the attention to vulnerable stakeholders,such as patients;and to optimize the design of policies at the meso-levels and micro-levels in order to enhance the systemicity and sustainability of policy implementation.

Objective To investigate the value of stress hyperglycemia ratio(SHR)in predicting symptomatic intracranial hemorrhage(sICH)after successful recanalization of endovascular ther-apy(EVT)in patients with non-diabetic acute large vascular occlusive(LVO)stroke.Methods A total of 150 non-diabetic patients with acute stroke due to LVO admitted in our hospital from June 2022 to June 2024 were recruited,and all of them underwent EVT and obtained successful recanalization.According to whether sICH occurred 24 h after surgery,they were divided into a sICH group(15 cases)and a non-sICH group(135 cases).They were also assigned into a poor prognosis group(55 cases)and a good prognosis group(95 cases)according to the prognosis in 3 months after surgery.The general clinical data were compared between groups,and multivariate logistic regression analysis was used to identify the influencing factors for sICH and prognosis after successful EVT recanalization in the non-diabetic acute stroke patients.ROC curves were plotted to analyze the predictive value of SHR in sICH and prognosis after successful EVT reca-nalization in the patients.Results Significantly larger proportion of embolic occlusion,higher NIHSS score at admission and SHR were observed in the sICH group than the non-SICH group(66.67％vs 37.04％,P＜0.05;20.15±3.68 vs 15.62±3.10,P＜0.01;1.25±0.25 vs 1.01±0.28,P＜0.01).The poor prognosis group had obviously larger female ratio,advanced age,higher NIHSS score at admission,larger proportion of previous stroke history and higher SHR than the good prognosis group(49.09％vs 29.47％,P＜0.05;75.41±5.38 years old vs 72.56±5.63 years old,P＜0.01;18.65±3.71 vs 16.27±3.21,P＜0.01;32.73％vs 14.74％,P＜0.05;1.16±0.23 vs 1.02±0.25,P＜0.01).Multivariate logistic regression analysis showed that embolic occlusion,NIHSS score at admission and SHR were risk factors for sICH after successful EVT recanaliza-tion in non-diabetic acute stroke due to LVO(OR=2.038,95％CI:1.138-4.234,P=0.000;OR=2.026,95％CI:1.173-4.317,P=0.000;OR=1.996,95％CI:1.101-4.027,P=0.000),while gender,age,NIHSS score at admission,previous stroke history,and SHR were risk factors for poor prognosis in the patients(OR=2.004,95％CI:1.085-3.407,P=0.000;OR=2.075,95％CI:1.138-4.067,P=0.000;OR=2.010,95％CI:1.208-4.106,P=0.000;OR=2.034,95％CI:1.137-4.821,P=0.000;OR=2.038,95％CI:1.138-4.234,P=0.000).ROC curve analysis showed that the AUC value of SHR in predicting sICH and prognosis of the non-diabetic patients with acute stroke due to LVO after successful EVT recanalization was 0.797 and 0.823,with a sensitivity of 80.00％and 81.82％,and a specificity of 82.22％and 80.00％,respectively.Conclusion SHR can affect sICH and prognosis after successful EVT recanalization in non-diabetic acute LVO stroke patients,and it has a certain predictive value for sICH and poor prog-nosis of the patients.