OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

Objective To explore the safety and feasibility of 5G remote robot-assisted thoracoscopic anatomic lobectomy and segmentectomy. Methods A retrospective analysis was conducted on patients who underwent 5G remote robot-assisted thoracoscopic anatomic lobectomy or segmentectomy between July and September 2024. The surgeries were performed collaboratively by Shanghai Chest Hospital, Affiliated Hospital of Yangzhou University, and The First Affiliated Hospital of Nanchang University. Perioperative outcomes were recorded and analyzed. Results Ten patients were included, comprising 4 anatomic lobectomies and 6 segmentectomies. The median age was 61.0 (56.0, 72.0) years. The median intraoperative bi-directional network latency was 52.5 (39.0, 54.0) ms. There were no instances of network interruption, robot-related adverse events, or conversions to open thoracotomy. The median postoperative chest tube drainage volume was 500.0 (375.0, 600.0) mL, and the median hospital stay was 5.5 (4.0, 6.0) days. No complications of Clavien-Dindo grade Ⅱor higher occurred. All patients were recurrence-free and alive during the 6-month postoperative follow-up period. Conclusion 5G remote robot-assisted thoracoscopic surgery demonstrates high safety and operational stability. This technology shows promising potential for clinical application and is worthy of further development and utilization.

Curcumin (Cur), a natural polyphenolic compound extracted from the rhizomes of plants belonging to the Zingiberaceae and Araceae families, has attracted considerable interest for its remarkable antioxidant, anti-inflammatory, antibacterial, and anticancer activities. Extensive studies have focused on its potential in treating various diseases, including cancers, neurodegenerative diseases, inflammation, and autoimmune disorders. However, its clinical application has been hampered by inherent physicochemical challenges, such as poor aqueous solubility, short half-life, and low bioavailability. To address these challenges, nanodrug delivery systems have been developed to improve the pharmacokinetic and pharmacodynamic profiles of curcumin, thereby enhancing its therapeutic efficacy. This review summarizes the pharmacological activities and underlying mechanisms of curcumin, encompassing its antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial effects. Furthermore, it highlights the significant advancements achieved through the development of curcumin-based nanomedicines. By synthesizing current findings, this review aims to provide insights that may inspire innovative strategies for the future design and broader applications of curcumin nanomedicines.

Objective: To investigate the situation and influencing factors of school bullying experienced by primary and middle school students, so as to provide the basis for formulating school bullying intervention measures and promoting students' physical and mental health development. Methods: All the counties (cities, districts) in Zhejiang Province were stratified to urban and suburban areas, primary, junior high and senior high school students were selected using a stratified cluster sampling method. Basic information, lifestyle and school bullying were collected through questionnaire surveys. Factors affecting school bullying experienced by primary and middle school students were analyzed using a multivariable logistic regression model. Results: Totally 137 846 valid questionnaires were recovered, with an effective recovery rate of 97.17%. There were 72 526 males (52.61%) and 65 320 females (47.39%). There were 47 561 primary school students (34.50%), 47 701 junior high school students (34.61%) and 42 584 senior high school students (30.89%). A total of 3 987 students suffered from school bullying, accounting for 2.89%. The proportions of being maliciously teased, being intentionally excluded from group activities/isolated, being teased about physical defects or appearance, being hit/kicked/pushed/shoved/locked in a room, being threatened, and being extorted for money were 2.04%, 1.18%, 1.11%, 0.86%, 0.84% and 0.83%, respectively. Multivariable logistic regression analysis showed that the students who were males (OR=1.122, 95%CI: 1.048-1.202), lived in suburban areas (OR=1.322, 95%CI: 1.233-1.418), lived in areas with medium (OR=1.086, 95%CI: 1.006-1.173) or underdeveloped (OR=1.298, 95%CI: 1.191-1.415) economic level, had higher academic levels (junior high school, OR=1.380, 95%CI: 1.270-1.499; senior high school, OR=1.210, 95%CI: 1.083-1.351), lived on campus (OR=1.489, 95%CI: 1.372-1.616), engaged in fights (OR=6.029, 95%CI: 5.585-6.509), attempted to smoke (OR=1.320, 95%CI: 1.128-1.545), drank (OR=1.735, 95%CI: 1.575-1.912), were scolded and beaten by parents (OR=1.972, 95%CI: 1.822-2.135) and were obese (OR=1.240, 95%CI: 1.132-1.360) were more likely to experience school bullying. Conclusion The harm of school bullying to the physical and mental health of primary and middle school students should be taken seriously, and active policy measures should be adopted to strengthen intervention.

In the context of medical insurance payment reform,the sample hospital has implemented performance management optimization to effectively address the challenges posed by diagnosis-intervention packet(DIP)payment.Reform measures focused on disease quality,rational diagnosis and treatment,operational management,medical technological value,and policy orientation,and they have significantly optimized service ability and performance evaluation indexes of the hospital.Main achievements included a reduction in the cost consumption index and an increase in the clinical performance index,with the overall DIP payment rate increasing from 88.86%to 103.23%and a marked improvement in operational management.The quality control and operational efficiency of the hospital have been effectively enhanced by choosing proper DIP payment evaluation indexes and improving performance management,and provided strong support for the high-quality development of the hospital.

Objective To establish a homozygous zebrafish map3k15 knockout line using CRISPR/Cas9 gene editing technology so to provide an animal model for investigation of potential role of map3k15 in renal diseases.Methods 1)Analyzing the expression pattern of map3k15 in zebrafish;2)Establishing a homozygous map3k15 knockout zebrafish line using CRISPR/Cas9;3)Observing the phenotypic effects of map3k15 deficiency in ze-brafish.Results 1)map3k15 was expressed in the zebrafish pronephros,and map3k15/map3k15 protein was found highly conserved across species;2)map3k15-/-mutant zebrafish model was constructed with+2 bp mutation and+1 bp mutation;3)map3k15 mutant zebrafish exhibited edema in yolk sac,pericardium and head during embryonic development.Conclusions A homozygous zebrafish map3k15 knockout line is successfully developed which may provide an important model for future research on the role of map3k15 in renal development and disease.

To enhance the therapeutic efficacy of the baicalin-berberine complex(BA-BBR) in the treatment of ulcerative colitis(UC), BA-BBR nanocrystal microspheres(BA-BBR NC MS) were prepared using the dropping method. The microspheres were characterized in terms of morphology, particle size, differential scanning calorimetry(DSC), and powder X-ray diffraction(XRD). The release profiles of BA and BBR from the microspheres were measured, and the drug release mechanism was investigated. A rat model of UC was induced by 5% dextran sodium sulfate(DSS) and treated continuously for 7 days to evaluate the therapeutic effects of different formulations. The results showed that the prepared BA-BBR MS and BA-BBR NC MS were uniform gel spheres with particle sizes of(1.77±0.16) mm and(1.67±0.08) mm, respectively. After drying, the gels collapsed inward and exhibited a rough surface. During the preparation process, the BA-BBR nanocrystals(BA-BBR NC) were uniformly encapsulated within the microspheres. The release profiles of the microspheres followed a first-order kinetic model, and the 12-hour cumulative release of BA and BBR from BA-BBR NC MS was higher than that from BA-BBR MS. Compared with BA-BBR, BA-BBR NC, and BA-BBR MS, BA-BBR NC MS further alleviated UC symptoms in rats, most significantly reducing the levels of TNF-α, IL-1β, IL-6, and MPO, while increasing the level of IL-4 in colon tissues. These results indicate that BA-BBR NC MS, based on a "nano-in-micro" design, can deliver BA-BBR to the intestine and exert significant therapeutic effects in a UC rat model, suggesting it as a promising new strategy for the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Rats ; Nanoparticles/chemistry* ; Microspheres ; Male ; Berberine/administration & dosage* ; Flavonoids/administration & dosage* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Particle Size ; Tumor Necrosis Factor-alpha/immunology* ; Drug Liberation ; Drug Compounding

In this report, the protective effect and molecular mechanism of Chaihu Shugan San-containing serum on corticosterone(CORT)-induced mitochondrial damage in pheochromocytoma(PC12) cells was studied based on CORT-induced rat PC12 cell model. The cultured cells were divided into five groups: blank control group, CORT group(400 μmol·L~(-1) CORT), Chaihu Shugan San-containing serum group(400 μmol·L~(-1) CORT + 10% Chaihu Shugan San-containing serum), control serum group(400 μmol·L~(-1) CORT + 10% control serum), and fluoxetine group(400 μmol·L~(-1) CORT + 10% fluoxetine-containing serum). The study was carried out by cell activity detection, mitochondrial morphology observation, membrane potential measurement, energy metabolism analysis, and mitochondrial dynamics-related protein detection. The results showed that CORT treatment significantly reduced the survival rate of PC12 cells, altered mitochondrial morphology, and decreased mitochondrial membrane potential and adenosine triphosphate(ATP) synthetic rate. Both Chaihu Shugan San-and fluoxetine-containing serum significantly increased the survival rate of CORT-treated PC12 cells and the ATP synthetic rate in the mitochondria. Unlike fluoxetine, Chaihu Shugan San-containing serum significantly inhibited the decrease in mitochondrial membrane potential caused by CORT and increased the oxygen consumption rate(OCR) values of both mitochondrial maximum respiration and reserve respiration capacity. Western blot analysis showed that CORT induced upregulated protein expressions of dynamin-related protein 1(Drp1) and peroxisome proliferator-activated receptor gamma co-activator 1α(PGC-1α) in PC12 cells and specific protein expression of optic atrophy protein 1(OPA1), yet it repressed the protein expressions of silent information regulator 1(SIRT1) and mitochondrial fusion protein 1(Mfn1) in PC12 cells. Both Chaihu Shugan San-and fluoxetine-containing serum significantly inhibited the protein expression of Drp1. However, only Chaihu Shugan San-containing serum could significantly inhibit the CORT-induced upregulation protein of PGC-1α. RESULTS:: herein suggest that Chaihu Shugan San-containing serum can alleviate CORT-induced damage in PC12 cells, which may be related to the mitochondrial fragmentation/lipid peroxidation protection by Drp1 inhibition, as well as mitochondrial dynamics and energy metabolism mediated by PGC-1α/SIRT1 signaling pathway.
Animals ; PC12 Cells ; Rats ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Corticosterone/adverse effects* ; Membrane Potential, Mitochondrial/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Protective Agents/pharmacology* ; Cell Survival/drug effects*