OBJECTIVE To evaluate the cost-effectiveness of iruplinalkib for ALK-positive non-small cell lung cancer （NSCLC） patients who had not previously received ALK-tyrosine kinase inhibitors （TKIs） from the perspective of the Chinese healthcare system. METHODS Based on the INSPIRE clinical trial， a three-health state partitioned survival model was developed to simulate the progression of disease， with model cycle of 3 weeks and a life-year time range of 15 years； the discount rate was 5%. For the treatment of ALK-positive advanced NSCLC， total cost， quality-adjusted life year （QALY）， and incremental cost- effectiveness ratio （ICER） were compared between iruplinalkib and crizotinib； using 1-3 times China’s per capita gross domestic product （GDP） （89 358-268 074 yuan） in 2023 as the willingness-to-pay （WTP） threshold， the cost-effectiveness of two regimens were compared. The sensitivity analysis and scenario analysis （altering the distribution of survival curves， utility values） were conducted to assess model robustness. RESULTS Compared with the crizotinib regimen， the ICER for the iruplinalkib regimen was 194 412.74 yuan/QALY， which was below the WTP threshold of three times China’s per capita GDP in 2023 yuan）. The results under the scenario of altering the survival curve distribution were consistent with the base case analysis. However， after increasing the utility value of the disease progression state， the ICER exceeded the WTP threshold， and iruplinalkib no longer had a cost-effective advantage. The results of the one-way sensitivity analysis indicated that the cost of iruplinalkib and the utility values of disease progression states had a significant impact on the ICER. The probabilistic sensitivity analysis confirmed the robustness of the base case analysis results. CONCLUSIONS From the perspective of China’s healthcare system， compared with crizotinib regimen， the therapy with iruplinalkib is cost-effective for ALK-positive NSCLC patients who have not previously received ALK-TKIs.

The three-dimensional (3D) printed bone tissue repair guide scaffold is considered a promising method for treating bone defect repair. In this experiment, chitosan (CS), sodium alginate (SA), and mineralized collagen (MC) were combined and 3D printed to form scaffolds. The experimental results showed that the printability of the scaffold was improved with the increase of chitosan concentration. Infrared spectroscopy analysis confirmed that the scaffold formed a cross-linked network through electrostatic interaction between chitosan and sodium alginate under acidic conditions, and X-ray diffraction results showed the presence of characteristic peaks of hydroxyapatite, indicating the incorporation of mineralized collagen into the scaffold system. In the in vitro collagen release experiments, a weakly alkaline environment was found to accelerate the release rate of collagen, and the release amount increased significantly with a lower concentration of chitosan. Cell experiments showed that scaffolds loaded with mineralized collagen could significantly promote cell proliferation activity and alkaline phosphatase expression. The subcutaneous implantation experiment further verified the biocompatibility of the material, and the implantation of printed scaffolds did not cause significant inflammatory reactions. Histological analysis showed no abnormal pathological changes in the surrounding tissues. Therefore, incorporating mineralized collagen into sodium alginate/chitosan scaffolds is believed to be a new tissue engineering and regeneration strategy for achieving enhanced osteogenic differentiation through the slow release of collagen.
Chitosan/chemistry* ; Alginates/chemistry* ; Tissue Scaffolds/chemistry* ; Printing, Three-Dimensional ; Osteogenesis ; Collagen/chemistry* ; Cell Differentiation ; Animals ; Tissue Engineering/methods* ; Cell Proliferation ; Biocompatible Materials ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry*

Small cell lung cancer (SCLC) is the thoracic malignant tumor and accounts for about 15% of lung malignancies and transfer often occurs by the time of diagnosis. Extensive stage-small cell lung cancer (ES-SCLC) accounts for about 2/3 of all SCLC. For many years, radiotherapy has occupied an important position in the treatment of SCLC, especially in the treatment of ES-SCLC, because SCLC is more sensitive to radiotherapy. However, in recent years, immune checkpoint inhibitor has shown more excellent antitumor activity in the treatment of ES-SCLC and become the mainstream argument for the treatment of ES-SCLC. However, will radiotherapy be buried by the times among the therapeutic approaches for ES-SCLC? In this article, we will review the clinical progress of radiotherapy, immunotherapy and combination therapy for ES-SCLC.
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Humans ; Small Cell Lung Carcinoma/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy ; Neoplasm Staging ; Radiotherapy/methods* ; Combined Modality Therapy

Objective To investigate the safety and efficacy of combined confluence microdissection or balloon dilatation followed by laparoscopic transcystic common bile duct exploration (LTCBDE) in day surgery laparoscopic cholecystectomy. Methods The clinical data of 203 patients with day surgery laparoscopic cholecystectomy combined with LTCBDE from June 2021 to June 2024 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. They were divided into an observation group (59 cases, including 42 cases of confluent microdissection and 17 cases of balloon dilatation) and a conventional group (144 cases) according to the surgical technique used. Baseline characteristics, intraoperative exploration results, operation time, postoperative recovery and complications were compared between the two groups. Results The history of preoperative cholangitis or pancreatitis (P<0.001) was more common in the observation group. And total bilirubin level was significantly higher in the observation group than in the conventional group (P=0.035). The observation group had a longer operative time (P=0.014) and higher hospitalization costs (P=0.001), but there was no difference in intraoperative bleeding and postoperative discharge time. There were no serious postoperative complications in either group. Conclusions Under the premise of strict patient screening, day surgery LTCBDE combined with confluence microdissection or balloon dilatation can effectively solve the problem of difficult choledochoscopic access, with high safety and thoroughness of exploration. Both techniques provide a feasible minimally observation solution for day surgery biliary exploration.

The control and utilization of microorganisms in space-based animal culture constitute a pivotal challenge underpinning research domains such as space life sciences and extraterrestrial life-support system.This paper systematically examines the origins,transmission routes,and latent risks of microbial contamination in space-based animal culture facilities.A comprehensive analysis is conducted on the advancements in on-orbit implementation of microbial containment strategies,including physical filtration systems,antimicrobial surface coatings,and environmental parameter optimization.Additionally,the study evaluates the prospective applications of probiotic consortia and functionally engineered microorganisms in enhancing animal welfare,stabilizing biosphere conditions,and enabling closed-loop waste recycling.Notably,this work highlights the paradigm shift from reactive microbial suppression to proactive microbiome engineering in space-based animal husbandry,thereby establishing a theoretical framework for sustainable development of space-based animal culture.

Objective To explore the interaction mechanisms among different dimensions of online learning competence in undergraduates,providing scientific evidence for optimizing software design and online education strategies.Methods A cross-sectional study was conducted with 347 undergraduates from Kunming Medical University via an online questionnaire in October 2024.Reliability testing and exploratory factor analysis were performed using SPSS 26.0,while structural equation modeling was constructed with Amos 24.0.Results Driving force directly and positively influenced regulatory force(β=0.778,P<0.001)and reciprocal force(β=0.302,P=0.003),but had no significant direct effect on adaptive force(β=0.131,P=0.182).Regulatory force and reciprocal force both exerted direct positive effects on adaptive force(β=0.262,P=0.022;β=0.410,P<0.001).The indirect effect of driving force on adaptive force accounted for 78.1%of the total effect(P=0.007),with regulatory force showing a significant mediating role(β=0.178,P=0.023),while reciprocal force alone did not(β=0.108,P=0.060).A chain mediating effect(driving force→regulatory force→reciprocal force→adaptive force)was confirmed(β=0.124,P=0.004).Conclusion Driving force serves as the core of online learning competence,and adaptive capacity is enhanced through regulatory and reciprocal forces.To promote knowledge internalization and adaptability,it is required to optimize feedback mechanisms and deepen interactive designs in online learning platforms.

ObjectiveTo analyze and validate how Jiawei Sanpian decoction treats migraines by integrating network pharmacology, molecular docking technology, and experimental studies.MethodUsing network pharmacology, the chemical components and core target proteins of the Jiawei Sanpian decoction were analyzed. Key chemical components were docked with core targets using molecular docking, and the results were visualized. Nitroglycerin was injected into the dorsal cervical region to establish a rat migraine model. Finally, experiments were conducted to verify the effects of Jiawei Sanpian on related pathways and targets.ResultsFour notable chemical components were identified, namely, β-sitosterol, quercetin, mairin, and kaempferol. Five representative targets were identified, namely, insulin-like growth factor 1 (IGF-1), matrix metallopeptidase 2 (MMP-2), interleukin-2 (IL-2), superoxide dismutase 2 (SOD2), and inducible nitric oxide synthase (NOS2). Molecular docking results revealed that the minimum binding energies between the four chemical components and the five targets were below −5 kcal/mol, indicating favorable binding activity. Enzyme linked immunosorbent assay (ELISA) results demonstrated the efficacy of high-dose Jiawei Sanpian decoction in treating migraine by targeting IGF-1, IL-2, MMP-2, and SOD2 (P .001). Real-time quantitative polymerase chain reaction (RT-qPCR) results demonstrated the effectiveness of high-dose Jiawei Sanpian decoction in treating migraine by targeting IGF-1, IL-2, MMP-2, and SOD2 (P .001). After using erastin, the therapeutic effect of Jiawei Sanpian decoction declined.ConclusionThis study provides initial insights into the complex and multilayered therapeutic mechanisms of Jiawei Sanpian decoction in treating migraine, primarily through its diverse components, targets, and pathways. These findings indicate that Jiawei Sanpian decoction may exert its effects mainly through processes linked to the mitochondrial inflammatory pathway, thereby providing therapeutic benefits for migraine.

Objective To compare the efficacy of retroperitoneal robot-assisted laparoscopic partial nephrectomy(RALPN)in the treatment of ventral and dorsal renal tumor.Methods The clinical data of 131 patients with renal tumor who underwent retroperitoneal RALPN at our hospital during Jan.2021 and Feb.2024 were retrospectively analyzed.The patients were divided into the ventral renal tumor group(n=35)and dorsal renal tumor group(n=96)according to preoperative images.Perioperative outcomes and prognosis were compared between the two groups.Results All 131 surgeries were successfully completed without conversion to open surgery or abdominal organ injury.There were no significant differences in warm ischemia time[median(interquartile range,IQR):20(16.75)min vs.22(IQR:15.25)min],operation time[57.0(IQR:29.5)min vs.58.5(IQR:39.75)min],estimated intraoperative blood loss[50(IQR:80)mL vs.50(IQR:80)mL],proportion of patients with intraoperative blood transfusion(0 vs.2.1％),proportion of patients using four arms during operation(42.9％vs.37.5％),postoperative reduction of hemoglobin(Hb)[(-12.9±9.0)g/L vs.(-11.5±9.4)g/L],reduction of estimated glomerular filtration rate(eGFR)[(-3.8±12.4)mL/min vs.(-7.0±13.6)mL/min],postoperative hospital stay[4(IQR:0)d vs.4(IQR:2)d],and proportion of meeting"Trifecta"criteria(94.3％vs.86.5％,P＞0.05).During the median follow-up of 9.8(5.5,24.0)months,no death occurred,and no recurrence or metastasis were observed except that bone metastasis occurred in 1 patient in the dorsal renal tumor group.Conclusion Both ventral and dorsal renal tumors can be treated with retroperitoneal RALPN,and the surgical outcomes of both are comparable.

Objective:To discuss the effect of royal jelly acid(10-HDA)on the proliferation and migration of the human colon cancer SW620 cells based on the network pharmacology,and to clarify its related molecular mechanism.Methods:The active ingredients such as 10-HDA and their corresponding targets were retrieved by using the keyword"royal jelly"from the Traditiomal Chinese Medicine Systems Pharmacology(TMSCP)Database and the Traditiomal Chinese Medicine Integrated Database(TCMID);the small molecule targets were predicted by the Swiss Target Prediction Database.The GeneCards Database and the Online Mendelian Inheritance in Man(OMIM)Database were used to obtain the targets with the keyword"Colon Cancer";the protein-protein interaction(PPI)network was constructed by using the String Database and Cytoscape 3.8.0 Software to screen the core targets;the Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were analyzed by Metascape Database;the specific ingredient 10-HDA was screened for the in vitro activity experiments.The human colon cancer SW620 cells with good growth status were divided into control group and different doses(1,5,10,15,and 20 mmol·L-1)of 10-HDA groups.The viabilities of the cells in various groups were detected by MTT method and the survival rates of the cells were calculated.The SW620 cells were divided into control group,low dose(5 mmol·L-1)of 10-HDA group,middle dose(10 mmol·L-1)of 10-HDA group,and high dose(15 mmol·L-1)of 10-HDA group;Hoechst33342 staining method was used to observe the morphology of the cells in various groups;cell scratch test was used to detect the scratch healing rates of the cells in various groups;flow cytometry was used to detect the percentages of the cells at different cell cycles in various groups;biochemical method was used to detect the activities of total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)in the cells in various groups;Western blotting method was used to detect the expression levels of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),cysteine-containing aspartate proteolytic enzyme-3(Caspase-3),cysteine-containing aspartate proteolytic enzyme-9(Caspase-9),glycogen synthase kinase 3β(GSK3β),β-catenin,and cyclin D1 proteins in the cells in various groups.Results:Six active ingredients of royal jelly were screened out by the TCMSP Database,and 28 core targets of 10-HDA in the treatment of colon cancer were obtained.The GO function enrichment analysis mainly included the signaling pathways such as cell proliferation and apoptosis.The KEGG signaling pathway enrichment analysis included the cell cycle,prostate cancer,cell senescence,and p53 signaling pathways;the GSK3β/β-catenin signaling pathway was closely related to the cell cycle.Compared with control group,the viabilities of the cells in 5,10,15,and 20 mmol·L-110-HDA groups were decreased in a dose-dependent manner(P<0.05 or P<0.01),the numbers of apoptotic cells in different doses of 10-HDA groups were significantly increased,and the scratch healing rates of the cells were significantly decreased(P<0.05 or P<0.01);the percentages of the cells at S phase in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),the activities of T-AOC and SOD in the cells in different doses of 10-HDA groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the expression level of Bcl-2 protein in the cells in low dose of 10-HDA group was significantly decreased(P<0.01),and the expression level of GSK3β protein was significantly increased(P<0.05);compared with control group,the expression levels of Bax,Caspase-3,Caspase-9,and GSK3β proteins in the cells in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),and the expression levels of Bcl-2,β-catenin,and CyclinD1 proteins were significantly decreased(P<0.01).Conclusion:10-HDA can significantly inhibit the proliferation and migration of the colon cancer cells and promote the apoptosis and oxidation levels of the colon cancer cells,and its mechanism may be related to the activation of the GSK3β/β-catenin signaling pathway.

Objective To investigate the mechanism of circadian clock protein Bmal1(Bmal1)on renal injury with chronic periodontitis,we established an experimental rat periodontitis model.Methods Twelve male Wistar rats were randomly divided into control and periodontitis groups(n=6,each group).The first maxillary molars on both sides of the upper jaw of rats with periodontitis were ligated by using orthodontic ligature wires,whereas the control group re-ceived no intervention measures.After 8 weeks,clinical periodontal parameters,including probing depth,bleeding index,and tooth mobility,were evaluated in both groups.Micro-CT scanning and three-dimensional image recon-struction were performed on the maxillary bones of the rats for the assessment of alveolar bone resorption.Histopatholo-gical observations of periodontal and renal tissues were conducted using hematoxylin-eosin(HE)and periodic acid-Schiff(PAS)staining.Renal function indicators,such as creatinine,albumin,and blood urea nitrogen levels,and oxida-tive stress markers,including superoxide dismutase,glutathione,and malondialdehyde levels,were measured using bio-chemical assay kits.MitoSOX red staining was used to detect reactive oxygen species(ROS)content in the kidneys.The gene and protein expression levels of Bmal1,nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)in rat renal tissues were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)and immuno-histochemical staining.Results Micro-CT and HE staining results showed significant bone resorption and attachment loss in the maxillary first molar region of the periodontitis group.Histological examination through HE and PAS staining revealed substantial histopathological damage to the renal tissues of the rats in the periodontitis group.The findings of the assessment of renal function and oxidative stress markers indicated that the periodontitis group exhibited abnormal levels of oxidative stress,whereas the renal function levels showed abnormalities without statistical significance.Mito-SOX Red staining results showed that the content of ROS in the renal tissue of the periodontitis group was significantly higher than that of the control group,and RT-qPCR and immunohistochemistry results showed that the expression levels of Bmal1,Nrf2,and HO-1 in the renal tissues of the rats in the periodontitis group showed a decreasing trend.Conclu-sion Circadian clock protein Bmal1 plays an important role in the oxidative damage process involved in the renal of rats with periodontitis.