Dietary interventions such as fasting are gaining increasing attention for their synergistic effects in anti-tumor therapy, yet the precise underlying mechanisms remain incompletely understood. Recent research has unveiled a novel mode of cell death named “mitoxyperilysis”, providing a fresh perspective on the molecular mechanisms by which fasting may interfere with tumor treatment. This form of death is primarily triggered by the synergy between metabolic dysfunction and innate immune activation. Its mechanism involves the mTORC2 signaling pathway mediating prolonged abnormal contact between damaged mitochondria and the plasma membrane. This leads to massive local release of reactive oxygen species (ROS), which further induces lipid peroxidation of the plasma membrane, ultimately resulting in the physical rupture and death of the cell. The most significant distinction between mitoxyperilysis and classical cell death pathways lies in its independence from caspases and GSDMD. This comment aims to systematically elucidate the process, molecular mechanisms, and differences from other classical cell death pathways of mitoxyperilysis, while also exploring its potential for clinical translation in oncological diseases. Targeting induction of mitoxyperilysis may enhance the efficacy of existing anti-tumor drugs and overcome chemotherapy resistance. However, intervention protocols require further optimization to achieve an optimal balance between safety and therapeutic effectiveness in clinical application.

Objective To explore the correlation between lymph node metastasis and clinicopathological features of lung adenocarcinoma with diameter≤3 cm. Methods The clinicopathologic data of the patients with lung adenocarcinoma≤3 cm in diameter were retrospectively analyzed. The relationship between lymph node metastasis and age, gender, smoking history, pathological subtype, tumor diameter, pleural invasion, vascular invasion and other factors was analyzed. The risk factors of lymph node metastasis were analyzed by univariate and multivariate logistic regression. Results Finally 1 718 patients were collected, including 697 males and 1 021 females with an average age of (58.89±9.85) years. The total lymph node metastasis rate was 12.9%, among whom 452 patients of adenocarcinoma in situ and minimally invasive adenocarcinoma did not have lymph node metastasis, and the lymph node metastasis rate of invasive lung adenocarcinoma was 17.5%. Multivariate analysis showed that tumor diameter, micropapillary subtype, solid subtype, micropapillary component, solid component, vascular invasion and pleural invasion were independent risk factors for lymph node metastasis of invasive lung adenocarcinoma with diameter≤3 cm (P<0.05). While age, lepidic subtype and lepidic component were independent protective factors for lymph node metastasis (P<0.05). Conclusion Clinicopathological features can help predict lymph node metastasis of lung adenocarcinoma with diameter≤3 cm.

ObjectiveThis paper aims to investigate the effect and mechanism of Runmu Xiaoyao powder on mice with dry eye and the syndrome of liver depression-heat syndrome based on the toll-like receptor 4 （TLR4）/myeloid differentiation primary response protein 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsSixty-six C57BL/6J female mice were randomly divided into a normal group， a model group， a sodium hyaluronate group， and high-， medium-， and low-dose Runmu Xiaoyao powder groups， with 11 mice per group. Except for those in the normal group， mice in the other groups were subjected to mouse models with dry eye and liver depression-heat syndrome by instilling a benzalkonium chloride solution and applying chronic pain stimulation in a dry environment. After modeling， mice in the high-， medium-， and low-dose Runmu Xiaoyao powder groups were administered intragastrically with 29.7， 14.85， 7.43 g·kg^-1， respectively， twice a day for 14 consecutive days. The mice in the sodium hyaluronate group received 5 μL of sodium hyaluronate eye drops in each eye twice daily. The mice in the normal and model groups were administered intragastrically with an equal volume of deionized water. Measurements were taken of tear secretion in mice， irritability scores， corneal fluorescein staining， and histopathological changes in the cornea， lacrimal glands， meibomian glands， and liver tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-1β （IL-1β） and tumour necrosis factor-α （TNF-α） in serum. Immunohistochemistry （IHC） was used to detect the protein expression of IL-1β and TNF-α in corneal and lacrimal gland tissues. Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot were employed to detect the mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in corneal， lacrimal gland， and meibomian gland tissues. ResultsCompared with those in the normal group， mice in the model group exhibited significantly reduced tear secretion， significantly higher irritability scores， and more pronounced corneal fluorescence staining， with marked pathological damage observed in the cornea， lacrimal glands， meibomian glands， and liver tissue. IL-1β and TNF-α levels in serum were significantly elevated. The protein expressions of IL-1β and TNF-α in corneal and lacrimal gland tissues， as well as the mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in corneal， lacrimal gland， and meibomian gland tissues， were all significantly increased （P<0.01）. Compared with the model group， the sodium hyaluronate group and Runmu Xiaoyao powder groups with different doses exhibited increased tear secretion to varying degrees， alleviated corneal fluorescence staining and histopathological damage， reduced IL-1β and TNF-α levels in serum， and downregulated protein expressions of IL-1β and TNF-α in corneal and lacrimal gland tissues， as well as the mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in corneal， lacrimal gland， and meibomian gland tissues. The high-dose Runmu Xiaoyao powder group demonstrated a more pronounced effect， with multiple indicators showing superior results compared to those in the sodium hyaluronate group （P<0.05， P<0.01）. ConclusionRunmu Xiaoyao powder down-regulates the TLR4/MyD88/NF-κB signaling pathway activity in the cornea， lacrimal glands， and meibomian glands of model mice with dry eye and liver depression-heat syndrome， thereby suppressing inflammatory responses and mitigating ocular surface tissue damage. The therapeutic effect is dose-dependent， and the high-dose group exerts the most prominent effect.

BACKGROUND:How to repair bone defect has been a clinical problem for a long time.The effective ingredients of traditional Chinese medicine have good biological activity and therapeutic effect,and the combination of effective ingredients of traditional Chinese medicine and tissue engineering materials has a broad prospect in the field of bone repair.The combination of different effective ingredients of traditional Chinese medicine and scaffolds has similarities in their functional relationships. OBJECTIVE:To collect the cases of the combinations of effective ingredients of traditional Chinese medicine and scaffolds,then analogize tissue engineering scaffolds and effective ingredients of traditional Chinese medicine into two types of traditional Chinese medicine that generate compatibility relationships based on the inspiration of the compatibility of seven emotions and summarize the relationship between the two based on their functional relationships. METHODS:Relevant articles from January 1998 to January 2024 were searched in PubMed and China National Knowledge Infrastructure(CNKI),using English search terms"traditional Chinese medicine,Chinese medicine,traditional Chinese medicine monomers,bone defect,bone repair,bone tissue engineering,tissue engineering,scaffold"and Chinese search terms"traditional Chinese medicine,effective ingredients of traditional Chinese medicine,traditional Chinese medicine monomers,bone tissue engineering,bone tissue engineering scaffold,scaffold,tissue engineering,bone defect,bone repair."A total of 88 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)Both tissue engineering scaffold materials and active ingredients of traditional Chinese medicine have been widely used in the field of bone repair.Although they have obvious advantages in osteogenesis,there are still many shortcomings.Many studies are dedicated to preparing composite materials from the two,hoping to exert a detoxification and synergism through the interaction between the two.(2)Some drugs and materials can promote each other in osteogenesis,antibacterial,and promoting angiogenesis,enhancing their original effects.Inspired by the traditional concept of prescription compatibility,this article summarized it as a"Mutual promotion"relationship and provided examples to support it.(3)Some drugs can enhance the strength of materials,while some materials can achieve sustained release and controlled release effects,increase drug loading and stability,or achieve targeted delivery of drugs loaded on them.The article summarized this unilateral enhancement effect as a"Mutual assistance"relationship.(4)The combination of some traditional Chinese medicine and materials can reduce the toxic side effects of the other party.The article summarizes this detoxification relationship as"Mutual restraint and detoxification."(5)The article provided a new perspective on traditional Chinese medicine composite scaffolds,inspired by the seven emotions compatibility relationship and based on the classification of action relationships.It introduced traditional Chinese medicine concepts into the field of tissue engineering,providing new research ideas for subsequent researchers of composite scaffolds,and providing certain convenience in material selection and matching.

Background and purpose:The treatment of recurrent,metastatic,and treatment-na?ve advanced cervical cancer remains challenging.Immunotherapy in combination with chemotherapy and targeted therapy has shown preliminary clinical benefits,however,current evidence remains limited.This study aimed to evaluate the impact of camrelizumab combined with chemotherapy and targeted therapy on the prognosis of patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer.Methods:In this study,we conducted a retrospective analysis of the clinical data from 130 patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer admitted to Minhang Branch of Fudan University Shanghai Cancer Center from 2019 to 2025.The patients were categorized into the observation group(n=70),which included those who received camrelizumab with or without chemotherapy and targeted therapy,and the control group(n=60),including those who received chemotherapy and targeted therapy.Survival analysis was performed using the log-rank test,and univariate and multivariate Cox regression analyses were conducted to explore prognostic factors.This study was approved by the Ethics Committee of the Minhang Branch of Fudan University Shanghai Cancer Center[Approval number:(2024)Review No.(015)]and all informed consents were exempted.Results:The objective response rate(ORR)in the observation group was 72.9%,and the disease control rate(DCR)was 80.0%,which were significantly higher than those in the control group with an ORR of 20.0%(χ2=36.1,P＜0.001)and a DCR of 40.0%(χ2=21.8,P＜0.001).The median progression-free survival(PFS)in the observation group was not reached,significantly longer than that in the control group of 7.0 months(P＜0.001).Multivariate Cox regression analysis identified camrelizumab treatment as an independent protective factor for PFS(P＜0.001).Age,site of recurrence/metastasis,initial treatment approach,and histopathological type were not significantly associated with PFS.In the observation group,adverse events of grade 3 or higher were reported in 29 patients(41.4%),which primarily included vasculitis,hypothyroidism,hypersensitivity reactions,and diarrhea.Conclusion:The use of camrelizumab significantly improved treatment outcomes and prognosis for patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer,with significantly improved progression-free survival.Although a certain proportion of patients experienced adverse events of grade 3 or higher,the overall safety profile was acceptable.In clinical practice,immunotherapy offers a more effective treatment option for patients.

Objective To evaluate the diagnostic performance of the minimum-cost-path-based CT angiography-derived fractional flow reserve(MCP-FFR)and the deep learning-driven CT angiography-derived fractional flow reserve(DeepCL-FFR),and to particularly explore the potential value of the DeepCL algorithm in improving diagnostic accuracy within the"gray zone."Methods A retrospective analysis was conducted on 151 coronary vessels from 109 patients with coronary artery disease,who were hospitalized at the General Hospital of the People's Liberation Army between January 2020 and June 2021.Pearson correlation and Bland-Altman plots were employed to assess the correlation and agreement of the two CT-FFR methods with invasive FFR.A CT-FFR range of 0.70-0.80 was defined as the diagnostic"gray zone."The accuracy,sensitivity,specificity,positive predictive value,and negative predictive value for detecting hemodynamic abnormalities were calculated and analyzed.The DeLong test was used to compare the areas under the receiver operating characteristic curves(AUC)between the two CT-FFR calculation methods.Results Both CT-FFR methods exhibited a positive correlation with invasive FFR(MCP-FFR:r=0.75,P＜0.001;DeepCL-FFR:r=0.86,P＜0.001)and showed good agreement(MCP-FFR:mean difference=0.010,P=0.351;DeepCL-FFR:mean difference=-0.003,P=0.772).Both DeepCL-FFR(AUC 0.97,95％CI 0.94-0.99)and MCP-FFR(AUC 0.92,95％CI 0.88-0.97)demonstrated favorable diagnostic performance for detecting hemodynamic abnormalities(P=0.122).In the"gray zone"for hemodynamic abnormality,the diagnostic accuracy of MCP-FFR was 68.8％,whereas DeepCL-FFR increased it to 89.7％.DeepCL-FFR also exhibited superior diagnostic performance(AUC 0.89,95％CI 0.73-0.99)within the"gray zone,"which was significantly higher than that of MCP-FFR(AUC 0.71,95％CI 0.54-0.87)(P＜0.001).Conclusions The deep learning-driven coronary centerline extraction algorithm,DeepCL,demonstrates superior diagnostic performance in CT-FFR for detecting hemodynamic abnormalities,particularly by significantly improving diagnostic accuracy in the"gray zone."

Objective:To evaluate the effectiveness of a workshop-driven interactive teaching model in clinical alarm training for undergraduate nursing interns in the intensive care unit (ICU).Methods:A total of 120 undergraduate nursing students who interned in the ICU from November 2023 to April 2024 were enrolled and randomly assigned using a random number table into a control group ( n=60, traditional teaching) and an intervention group ( n=60, workshop-driven interactive teaching). Clinical alarm knowledge, attitudes, and practices (KAP); perception of patient safety culture; and training satisfaction were assessed before and after the training using validated questionnaires. Differences between groups were analyzed using independent sample t-test, paired sample t-test, chi-square test, and the Mann-Whitney U test with SPSS 22.0. Results:There were no significant differences between the two groups in clinical alarm KAP scores or patient safety culture perception scores before the training ( P>0.05). After the training, the intervention group showed significantly higher scores in clinical alarm KAP [(127.58±6.45) vs. (123.48±7.61), t=3.17, P=0.002] and patient safety culture perception [(99.44±9.17) vs. (95.45±12.03), t=-2.04, P=0.044] compared with the control group. Satisfaction with training content, teaching quality, and overall instructional design was significantly higher in the intervention group than in the control group ( P<0.05). Within-group comparisons showed that the intervention group had significant improvements in clinical alarm KAP [(127.58±6.45) vs. (120.10±10.25), t=-5.10, P<0.001] and patient safety culture perception [(99.44±9.17) vs. (94.46±12.12), t=-2.65, P=0.010] after training. No significant changes were observed in the control group after training ( P>0.05). Conclusions:The workshop-driven interactive teaching model can effectively enhance the clinical alarm KAP levels and patient safety culture perception among undergraduate nursing interns in the ICU. This teaching approach provides a scientific basis for optimizing clinical alarm education and cultivating high-quality nursing professionals.

Objective:To evaluate the music perception ability and appraisal status of cochlear implant adult users, then to compare those with normal-hearing subjects.Methods:The Iowa Musical Background and Appreciation Questionnaire (IMBAQ) was conducted to evaluate 20 cases of post-lingual deafness cochlear implant recipients (9 males, 11 females) aged 12-61(mean=28.8 yrs). Those music perception abilities were tested via Music Perceptional Evaluation Platform. Two kinds of tone(C#3, C#5)were carried out in the music perception test, including the Just Noticeable Difference (JND) Test, the Pitch-Direction Discrimination (PDD) Test and the Melody Contour Identification (MCI) Test. Meanwhile, the timbre identification tests were received by both normal hearing and cochlear implant patients.Results:The total outcomes of cochlear implant recipients were inferior to the normal hearing subjects ( P<0.05). Both of the thresholds of JND ( P=0.001) and PDD ( P<0.001) had a significant difference, while comparing the two frequency values (C#3 and C#5) in cochlear implant adult users. IMBAQ results indicated the lower post-implantation music appreciation and engagement compared to pre-deafness levels. The longer duration of formal music training was positively correlated with better music perception performance in CI recipients. Conclusions:There still has a big gap between the cochlear implant group and normal hearing group in the music perception test. And different frequency value causes effect on the result of cochlear implant patient group.

Objective To explore the effects of honokiol on malignant phenotypes in PANC-1 cells and its mechanisms.Methods In our experiments,MTT assay was used to detect the effects of honokiol on PANC-1 cell viability.The migration and invasion of PANC-1 cells were evaluated by wound healing assay and Transwell assay.The glycolysis level was detected by ELISA and ECAR.Western blotting was used to detect the expressions of OCT4,SOX2,Nanog,LDHA,HK2 and Raf/MEK/ERK pathway related proteins.Results Honokiol could significantly inhibit the migration and invasion abilities of PANC-1 cells(migration rate and invasion rate being 13.78％-59.45％and 12.47％-44.47％,respectively).Mechanistically,honokiol targeted Raf/MEK/ERK signaling pathway and significantly reduced the expressions of LDHA(29.60％)and HK2(31.98％),thereby reducing glycolysis and lactate production(29.42％-56.31％,compared with control group P＜0.05).This metabolic reprogramming effect ultimately inhibited the protein expressions of OCT4(33.38％),SOX2(33.07％),and Nanog(26.24％).Conclusion Honokiol treatment can inhibit the cell viability,migration and invasion abilities of PANC-1 cells.The mechanisms are related to the inhibition of glycolysis and cell stemness by regulating Raf/MEK/ERK pathway.

Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.