Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.

Objective To evaluate the impact of dynamic changes in proteinuria on the deterio-ration of renal function in patients with IgA nephropathy(IgAN).Methods A total of 105 patients with IgAN were selected as the study subjects,and they had complete 3-year follow-up data.Based on the initial 24 h proteinuria levels,the patients were categorized into mild proteinuria(group A,＜1.0 g),moderate proteinuria(group B,1.0 to 3.0g)and severe proteinuria(group C,＞3.0 g).The primary endpoint of this study was the incidence of an annual decline rate of ≥30％in the esti-mated glomerular filtration rate(eGFR),while the secondary endpoint was the occurrence of end-stage renal disease events.Survival analysis was conducted using the Kaplan-Meier method.Cox pro-portional hazards regression model was employed to assess the impact of different clinical variables on renal function decline.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive efficacy of changes in proteinuria levels on disease progression.Results Statistically sig-nificant differences were observed among the three groups in terms of the proportion of patients with eGFR decline rate of ≥30％and hormone therapy(P＜0.05).The mean survival time was 35.686 months in the group A,34.644 months in the group B,and 29.760 months in the group C.Both the initial proteinuria level(OR=4.068,P＜0.001)and the change in proteinuria level(OR=3.914,P＜0.001)were significant predictors of renal function decline.The initial proteinuria level[area under the curve(AUC)=0.825,P＜0.001]demonstrated higher predictive efficacy for the deterioration of IgAN compared to the change in proteinuria level(AUC=0.643,P＜0.05).Con-clusion The initial proteinuria level and its dynamic changes are important predictors of renal func-tion progression in patients with IgAN.Monitoring the dynamic changes in proteinuria can facilitate early intervention in renal function deterioration.

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Objective To measure the transaction costs of compact urban medical groups and analyze the evaluation of transaction costs by various stakeholders.Methods Using the typical sampling method,it took the Compact Urban Medical Group of J District General Hospital in Zhengzhou City,Henan Province as an example.A questionnaire sur-vey was conducted on the construction party(health administration department,leading hospital and member units)and related staff from January 19 to 24,2024.The contents of the survey included institutional statements,basic information of the respondents,relevant fees or costs of each participant,and the evaluation of transaction costs by the staff of each institutional participant.Results In 2023,the total transaction cost of District J Medical Group in Zhengzhou City was 75 811 014.49 yuan;the majority of transaction costs were borne by the leading hospi-tal(98.1％);all stakeholders confirmed the existence of transaction costs in the medical group,but there were dif-ferences in the perception of the manifestations and distribution of transaction costs(P＜0.05).Conclusion The transaction costs of compact urban medical group are high,most of which are borne by the leading hospital;The stakeholders have not yet clearly understood the form and distribution of transaction costs.The measures to deal with transaction costs include"facing up to the widespread existence of transaction costs","improving the compensation incentive mechanism"and"establishing a saving system supply path".

Objective To measure the transaction costs of compact county medical alliance and propose counter-measures.Methods Based on Williamson-Zhang Wuchang analysis paradigm,it established the measure matrix of transaction cost of compact county medical alliance.Through the typical sampling method,the medical community of D city in Haixi Prefecture,Qinghai Province was selected as a research example to carry out an empirical study.Results The total transaction cost of the compact county medical community was 6 292 500.00 yuan,the transac-tion cost of the leading hospital was 6 234 300.00 yuan,accounting for 99.07％,and the special investment of the leading hospital reached to 5 887 100.00 yuan,accounting for 94.43％.The total transaction cost of the 298 referred patients was 308 400.00 yuan,and the average transaction cost per patient was 1 035.05 yuan.Conclusion The transaction costs of compact county medical alliance was generally high,most of which was borne by the leading hospital,and the patients also had to bear the corresponding transaction costs.In the next stage,the transaction costs should be dealt with from three aspects,including recognizing the secrecy and universality of the transaction costs,establishing economical system supply and establishing a sound compensation mechanism.

Objective To measure the transaction costs of the health management alliance with the clue of the re-ferral treatment of patients with hypertension and diabetes.Methods Based on the Williamson-Zhang Wuchang analy-sis paradigm,a transaction cost measurement matrix of health management alliance was established.Through the typical sampling method,the health management alliance of County N in Shandong Province was selected as a re-search example to carry out empirical research.Results In 2023,the total transaction costs of the sampled health management alliance reached to 6 726 700.00 yuan,and the average transaction cost per referral patient was 3 846 yuan.The leading hospital accounted for 79.45％of the transaction cost,followed by the CDC.Meanwhile,busi-ness coordination cost accounted for 47.18％of the total transaction cost,and the average transaction cost per refer patient with hypertension or diabetes was 700.90 yuan.Conclusion The total transaction costs of the health manage-ment alliance was large,and it was mainly borne by the leading hospital.Patients also need to bear considerable transaction costs.The countermeasures included improving the service integration mechanism,establishing economi-cal system supply path,and coordinating actions between social health insurance system and health care system.

Objective To measure the transaction costs of compact urban medical groups and analyze the evaluation of transaction costs by various stakeholders.Methods Using the typical sampling method,it took the Compact Urban Medical Group of J District General Hospital in Zhengzhou City,Henan Province as an example.A questionnaire sur-vey was conducted on the construction party(health administration department,leading hospital and member units)and related staff from January 19 to 24,2024.The contents of the survey included institutional statements,basic information of the respondents,relevant fees or costs of each participant,and the evaluation of transaction costs by the staff of each institutional participant.Results In 2023,the total transaction cost of District J Medical Group in Zhengzhou City was 75 811 014.49 yuan;the majority of transaction costs were borne by the leading hospi-tal(98.1％);all stakeholders confirmed the existence of transaction costs in the medical group,but there were dif-ferences in the perception of the manifestations and distribution of transaction costs(P＜0.05).Conclusion The transaction costs of compact urban medical group are high,most of which are borne by the leading hospital;The stakeholders have not yet clearly understood the form and distribution of transaction costs.The measures to deal with transaction costs include"facing up to the widespread existence of transaction costs","improving the compensation incentive mechanism"and"establishing a saving system supply path".

Objective To measure the transaction costs of compact county medical alliance and propose counter-measures.Methods Based on Williamson-Zhang Wuchang analysis paradigm,it established the measure matrix of transaction cost of compact county medical alliance.Through the typical sampling method,the medical community of D city in Haixi Prefecture,Qinghai Province was selected as a research example to carry out an empirical study.Results The total transaction cost of the compact county medical community was 6 292 500.00 yuan,the transac-tion cost of the leading hospital was 6 234 300.00 yuan,accounting for 99.07％,and the special investment of the leading hospital reached to 5 887 100.00 yuan,accounting for 94.43％.The total transaction cost of the 298 referred patients was 308 400.00 yuan,and the average transaction cost per patient was 1 035.05 yuan.Conclusion The transaction costs of compact county medical alliance was generally high,most of which was borne by the leading hospital,and the patients also had to bear the corresponding transaction costs.In the next stage,the transaction costs should be dealt with from three aspects,including recognizing the secrecy and universality of the transaction costs,establishing economical system supply and establishing a sound compensation mechanism.

Objective To measure the transaction costs of the health management alliance with the clue of the re-ferral treatment of patients with hypertension and diabetes.Methods Based on the Williamson-Zhang Wuchang analy-sis paradigm,a transaction cost measurement matrix of health management alliance was established.Through the typical sampling method,the health management alliance of County N in Shandong Province was selected as a re-search example to carry out empirical research.Results In 2023,the total transaction costs of the sampled health management alliance reached to 6 726 700.00 yuan,and the average transaction cost per referral patient was 3 846 yuan.The leading hospital accounted for 79.45％of the transaction cost,followed by the CDC.Meanwhile,busi-ness coordination cost accounted for 47.18％of the total transaction cost,and the average transaction cost per refer patient with hypertension or diabetes was 700.90 yuan.Conclusion The total transaction costs of the health manage-ment alliance was large,and it was mainly borne by the leading hospital.Patients also need to bear considerable transaction costs.The countermeasures included improving the service integration mechanism,establishing economi-cal system supply path,and coordinating actions between social health insurance system and health care system.