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*

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.

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.

OBJECTIVE To analyze the changes of temporary abnormal intraepithelial papillary capillary loop(IPCL)in the surgical area of early glottic laryngeal cancer after CO2 laser resection.METHODS A retrospective study was conducted on early-stage glottic carcinoma patients who visited the Department of Otolaryngology,Head and Neck Surgery at the Second Affiliated Hospital from January 2017 to November 2023.Patients who underwent CO2 laser surgery accepted electronic laryngoscopy examination at 1 month,3 months,and 6 months postoperatively(including white light endoscopy and narrowband imaging endoscopy(NBI),and their medical history,treatment methods,laryngoscopy images,imaging data,and pathological results before and after treatment were systematically collected.The changes in laryngoscopy characteristics at different follow-up times after surgery were analyzed.RESULTS This study included 55 patients with non recurrent early glottic carcinoma who underwent CO2 laser surgery.At 1 month,3 months,and 6 months after surgery,there were significant differences in the proportion of patients with pseudomembrane coverage(72.73%vs.25.45%vs.7.27%),granulation formation(60.00%vs.34.55%vs.1.82%),and abnormal IPCL(23.64%vs.7.27%vs.0.00%)on the surface of the surgical area(P<0.001),and abnormal IPCL(mainly type Va and Vb)can be observed under NBI endoscopy from 1 month to 3 months after surgery.Within 6 months after surgery,the pseudomembrane detachment,granulation regression,scar formation,and abnormal IPCL in the surgical area disappeared.CONCLUSION Early glottic carcinoma patients may experience temporary abnormal IPCL within 3 months after receiving CO2 laser resection,but the abnormal IPCL could disappear within 6 months after surgery for some patients.Therefore,close observation is necessary within 6 months after surgery and there is no need for urgent biopsy.

This ENETS guidance for well-differentiated nonfunctioning pancreatic neuroendocrine tumours(NF-Pan-NET),which published on Journal of Neuroendocrinology(2023),has been developed by a multidisciplinary working group,and provides up-to-date and practical advice on the management of these tumours.In this guideline,the authors discussed 10 troublesome questions about clinical practice,and summarized the extensive experience of their centers treating patients with NF-Pan-NET,and suggested that multidisciplinary participation is an essential part of NF-Pan-NET diagnosis and treatment.This paper aims to interpret the key contents of the guidelines in order to provide standardized clinical diagnosis and treatment procedures in NF-Pan-NET.

Objective:To discuss the feasibility and safety of robot-assisted laparoscopic retroperitoneal tumor resection in prone position.Methods:From August 2023 to January 2024, a total of eight patients with retroperitoneal tumors from the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed, including two males and six females. The average age was (47.4±12.5) years, average BMI was (24.4±3.5) kg/m 2 and median ASA grade was 2(2, 3). Retroperitoneal tumors were identified preoperatively through CT or MRI. The imaging revealed 4 cases of adrenal tumors located on the left side, 2 on the right side, and 2 non-adrenal tumors situated on the left side. The preoperative diagnoses included 2 cases of non-functional adrenal tumors, 2 cases of pheochromocytoma, 1 case of Cushing’s syndrome, 1 case of metastatic renal cell carcinoma, and 2 cases of non-adrenal tumors. Robot-assisted laparoscopic retroperitoneal tumor resection was performed with all patients in prone position. The inferior margin of the fourth lumbar vertebra (L4) was determined by the line connecting the highest points of the iliac crests bilaterally. Subsequently, the inferior margins of the L1-L3 vertebrae were sequentially identified. The surgical field was then divided into three equal segments, utilizing the posterior midline of the spine and the midaxillary line as boundaries. The medial division was situated approximately at the lateral border of the vertical spinal muscles, while the lateral division was placed near the tip of the 12th rib. A longitudinal incision of approximately 3 cm in length was created within the lateral division between L2 and L3 for the insertion of a camera trocar. The extraperitoneal space was subsequently dilated using a self-made balloon, and two 8 mm trocars were placed as operative ports along the medial division and the midaxillary line, respectively, under finger guidance. Assistance trocars, one or two 12 mm in diameter, were introduced above the level of the iliac crest. During the operation, the extraperitoneal adipose tissue was removed and the Gerota's fascia was opened. For non-adrenal retroperitoneal tumours, the major blood vessels around the tumour were suspended and fixed, by titanium clips or Hem-o-lok clips to dissect the small arteries and veins, and the tumour was carefully isolated and completely resected. For adrenal tumours, the fat capsule around the upper pole of the kidney were removed, the adrenal gland was exposed, and then the tumour was removed completely along its capsule. If total adrenalectomy is performed, the central adrenal vein was clamped and dissected. The periphery of the adrenal gland was gradually dissected until the adrenal gland was completely removed.The perioperative data, including patient positioning time, trocar placement time, operation time, intraoperative blood loss, postoperative complications, postoperative hospital stay, and postoperative drainage tube removal time, as well as recurrence and metastasis, were recorded.Two patients underwent partial nephrectomy due to renal tumor, and only the time for retroperitoneal tumor resection was included in calculating operation time. Results:All 8 surgeries were successfully completed without dramatic blood pressure fluctuations.There was no conversion to open surgery or abdominal organ injury. The patient positioning time was (5.1±0.4) minutes, trocar placement time was (16.6±1.3) minutes, operation time was (28.8±13.8) minutes, intraoperative blood loss was (65.0±28.7) ml, postoperative hospital stay was (3.6±0.9) days, and drainage tube removal time was (2.8±1.0) days. No intraoperative or postoperative blood transfusions were required. Postoperatively diagnosed pathologies included: 2 cases of adrenal pheochromocytoma, 2 cases of adrenal sebaceous adenoma, 2 cases of retroperitoneal schwannoma, 1 case of adrenal myelolipoma, and 1 case of adrenal metastatic renal cell carcinoma. The average tumor size for all patients was (4.3±1.5) cm. After a follow-up of 2.0-7.2 months, there were no recorded postoperative complications, including haemorrhage, infections, acute hypotension, or adrenocortical insufficiency. Additionally, no evidence of tumor recurrence or metastasis was observed up during foolow-up.Conclusions:Robot-assisted laparoscopic retroperitoneal tumor resection in prone position could be a safe and feasible surgical approach with short operative time, low bleeding, and fast postoperative recovery.