Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective To evaluate the policy of human organ transplantation in China, aiming to provide theoretical basis for further optimizing the policy of human organ transplantation. Methods Based on text mining and statistical analysis, seven normative policies of human organ transplantation formulated by national government from 2000 to 2022 were quantitatively evaluated by constructing policy modeling consistency (PMC) with 10 first-level variables and 35 second-level variables. Results Among the seven policies, six were graded as excellent policies and one as perfect policy, with an average PMC index of 8.476. Except X₈ policy audience, the scores of other second-level variables of P5 were higher than or equal to the mean. The scores of all second-level variables of P1 were lower than or equal to the mean. P1 and P5 significantly differed in X₃ policy timeliness, X₄ policy norms and X₆ policy tools. P5 was more specific and relatively comprehensive in these aspects, and its score was significantly higher than that of P1. Conclusions Human organ transplantation policies in China are generally excellent, scientific and rational. Health administrative departments at all levels should pay attention to the grasp of policy timeliness, the combination of policy tools, and fully mobilize the initiative and enthusiasm of all policy audience to participate in organ transplantation management when formulating organ transplantation policies.

Glaucoma is one of blind causing diseases. The cup-to-disc ratio is the main basis for glaucoma screening. Therefore, it is of great significance to precisely segment the optic cup and disc. In this article, an optic cup and disc segmentation model based on the linear attention and dual attention is proposed. Firstly, the region of interest is located and cropped according to the characteristics of the optic disc. Secondly, linear attention residual network-34 (ResNet-34) is introduced as a feature extraction network. Finally, channel and spatial dual attention weights are generated by the linear attention output features, which are used to calibrate feature map in the decoder to obtain the optic cup and disc segmentation image. Experimental results show that the intersection over union of the optic disc and cup in Retinal Image Dataset for Optic Nerve Head Segmentation (DRISHTI-GS) dataset are 0.962 3 and 0.856 4, respectively, and the intersection over union of the optic disc and cup in retinal image database for optic nerve evaluation (RIM-ONE-V3) are 0.956 3 and 0.784 4, respectively. The proposed model is better than the comparison algorithm and has certain medical value in the early screening of glaucoma. In addition, this article uses knowledge distillation technology to generate two smaller models, which is beneficial to apply the models to embedded device.
Humans ; Optic Disk/diagnostic imaging* ; Glaucoma/diagnosis* ; Algorithms ; Diagnostic Techniques, Ophthalmological ; Databases, Factual

Objective To study the effect of multi-disciplinary team (MDT) management on the outcome in neonates with omphalocele.Method A retrospective non-randomized controlled clinical study was conducted.Neonates who were diagnosed as omphalocele and admitted to the surgical neonatal intensive care unit of the Guangzhou Women and Children Medical Center from December 2010 to December 2017 were collected.Because MDT was established in December 2014,infants were assigned into non-MDT group and MDT group according to their dates of admission.The characteristics and outcomes between non-MDT group and MDT group were compared using x2,t-test or rank-sum test.Multivariate analysis was performed by Logistic regression.Result A total of 91 neonates were included in the study,50 were in non-MDT group and 41 were in MDT group.The mortality in MDT group (2.4％,1/41) was lower than that in non-MDT group (18.0％,9/50),the difference was statistically significant (P ＜ 0.05).The median time of mechanical ventilation of giant omphalocele in non-MDT group (18.3 hours) was longer than that in MDT group (41.7 hours),the difference was also statistically significant (P ＜ 0.05).After adjusting for the associated confounding risk factors,the risk of death in non-MDT group was 54 times higher than that in MDTgroup (OR=54.19,95％CI2.64 ～1 113.49,P＜0.05).Conclusion There was significant association between the MDT management and the decreased risk of death of omphalocele.

Amino Acid Substitution ; Antineoplastic Agents/pharmacology* ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; Gastrointestinal Neoplasms/pathology* ; Humans ; MAP Kinase Signaling System/genetics* ; Mutation, Missense ; Receptor, ErbB-3/metabolism* ; Receptor, Fibroblast Growth Factor, Type 1/metabolism*

OBJECTIVETo study the pharmacokinetics and bioequivalence of asparaginase loaded in hyaluronic acid-graft-poly(ethylene glycol)/ sulfobutylether-β-cyclodextrin nanocapsules (AHSP) in SD rats.

METHODSThe morphology of AHSP was observed under the transmission electron microscope and the particle size and zeta potential were measured. AHSP and free asparaginase were intravenously injected in rats, and the plasma asparaginase activity was measured at different time points after the injections. The pharmacokinetic parameters were calculated using the software DAS 2.1.1 to assess the bioequivalence of AHSP and free asparaginase.

RESULTSAHSP had an average particle size of 413.80∓10.97 nm with a zeta potential of -20.37∓2.38 mV. The AUC(0-48 h) of AHSP and free asparaginase was 137.34∓1.82 U/mL and 46.38 ∓1.98 U/mL, and their AUC(0-∞) was 164.66∓6.88 U/mL and 51.44∓3.01 U/mL with half-lives of 4.62∓0.60 h and 1.86∓0.38 h, respectively. Compared with free AN, AHSP exhibited increased AUC(0-48 h), AUC(0-∞), and half-life by 2.24, 2.55 and 2.32 folds, respectively. The 90% confidential intervals of AUC(0-48 h), AUC(0-∞) and Cmax of the tested formulation were 75.0%-76.5%, 74.3%-76.1%, and 95.1%-96.7%, respectively.

CONCLUSIONAHSP can improve the bioavailability and extend the biological half-life of asparaginase in rats, and AHSP and free asparaginase are not bioequivalent.

Animals ; Area Under Curve ; Asparaginase ; pharmacokinetics ; Biological Availability ; Half-Life ; Injections, Intravenous ; Nanocapsules ; Rats ; Rats, Sprague-Dawley ; Therapeutic Equivalency

OBJECTIVETo study the radiobiological characteristics of a HepG2 cell line with mitochondrial DNA (mtDNA) deletion.

METHODSHepG2 cells were cultured in a medium containing ethidium bromide, acetylformic acid and uracil. The HepG2 cell line with mtDNA deletion (ρ(0)HepG2 cells) were acquired after 30 subcultures by limited dilution cloning. The cell survival was then observed in the absence of acetylformic acid and uracil, and the total mtDNA deletion in the cells was confirmed by PCR. The radiosensitivity of HepG2 and ρ(0)HepG2 cells was evaluated by exposure to gradient doses of 6 MV X ray irradiation. The cell apoptosis was assessed following a 2 Gy X-ray exposure with Hochest33342 staining, and the invasiveness of ρ(0)HepG2 cells was measured by Transwell assay.

RESULTSHepG2 cells could survive 30 subcultures in the presence of ethidium bromide, and massive cell death occurred after removal of acetylformic acid and uracil from the medium. PCR confirmed total mtDNA deletion from ρ(0)HepG2 cells, whose α/β value was significantly lower than that of HepG2 cells. ρ(0)Hep-G2 cells showed an obviously lowered cell apoptosis rate following X-ray exposure with enhanced cell invasiveness.

CONCLUSIONHepG2 cells can be induced by ethidium bromide into ρ(0)HepG2 cells with an increased radiation resistance, anti-apoptosis ability and cell invasiveness.

Apoptosis ; Culture Media ; chemistry ; DNA, Mitochondrial ; genetics ; Ethidium ; chemistry ; Hep G2 Cells ; radiation effects ; Humans ; Radiation Tolerance ; genetics ; Sequence Deletion ; X-Rays

Objective To study the radiobiological characteristics of a HepG2 cell line with mitochondrial DNA (mtDNA) deletion. Methods HepG2 cells were cultured in a medium containing ethidium bromide, acetylformic acid and uracil. The HepG2 cell line with mtDNA deletion (ρ0HepG2 cells) were acquired after 30 subcultures by limited dilution cloning. The cell survival was then observed in the absence of acetylformic acid and uracil, and the total mtDNA deletion in the cells was confirmed by PCR. The radiosensitivity of HepG2 andρ0HepG2 cells was evaluated by exposure to gradient doses of 6 MV X ray irradiation. The cell apoptosis was assessed following a 2 Gy X-ray exposure with Hochest33342 staining, and the invasiveness of ρ0HepG2 cells was measured by Transwell assay. Results HepG2 cells could survive 30 subcultures in the presence of ethidium bromide, and massive cell death occurred after removal of acetylformic acid and uracil from the medium. PCR confirmed total mtDNA deletion fromρ0HepG2 cells, whoseα/βvalue was significantly lower than that of HepG2 cells.ρ0Hep-G2 cells showed an obviously lowered cell apoptosis rate following X-ray exposure with enhanced cell invasiveness. Conclusion HepG2 cells can be induced by ethidium bromide intoρ0HepG2 cells with an increased radiation resistance, anti-apoptosis ability and cell invasiveness.

Objective To study the radiobiological characteristics of a HepG2 cell line with mitochondrial DNA (mtDNA) deletion. Methods HepG2 cells were cultured in a medium containing ethidium bromide, acetylformic acid and uracil. The HepG2 cell line with mtDNA deletion (ρ0HepG2 cells) were acquired after 30 subcultures by limited dilution cloning. The cell survival was then observed in the absence of acetylformic acid and uracil, and the total mtDNA deletion in the cells was confirmed by PCR. The radiosensitivity of HepG2 andρ0HepG2 cells was evaluated by exposure to gradient doses of 6 MV X ray irradiation. The cell apoptosis was assessed following a 2 Gy X-ray exposure with Hochest33342 staining, and the invasiveness of ρ0HepG2 cells was measured by Transwell assay. Results HepG2 cells could survive 30 subcultures in the presence of ethidium bromide, and massive cell death occurred after removal of acetylformic acid and uracil from the medium. PCR confirmed total mtDNA deletion fromρ0HepG2 cells, whoseα/βvalue was significantly lower than that of HepG2 cells.ρ0Hep-G2 cells showed an obviously lowered cell apoptosis rate following X-ray exposure with enhanced cell invasiveness. Conclusion HepG2 cells can be induced by ethidium bromide intoρ0HepG2 cells with an increased radiation resistance, anti-apoptosis ability and cell invasiveness.