ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

Based on advancements in modern medical research regarding the intricate connection between the endocrine and exocrine functions of the pancreas， as well as the relationship between pancreatic functions and traditional Chinese medicine （TCM） spleen system， this paper discussed the categorization of the pancreas. It is proposed that the pancreas is neither a true zang organ nor a fu organ， but possessed the attributes of an extraordinary fu-organ and can be classified under the spleen. The spleen governs transportation and transformation， ascent of the clear and dispersion of essence， which encompasses the endocrine and exocrine functions， and pancreatic enzymes and glucose-regulating hormones form the material basis for the spleen's function of dispersing essence. Diseases of the pancreas exhibit characteristics of both zang-organ deficiency and fu-organ excess， so treatment should simultaneously supplement zang-organ disease and regulate fu-organ disease when pancreas showing endocrine and exocrine co-morbidities， with focus on restoring the pancreas （spleen）'s dispersing essence function. Therapeutic strategies include supplementing spleen qi， nourishing spleen yin to strengthen spleen earth， unblocking spleen collaterals， raising spleen yang， and removing spleen turbidity to support the spleen's dispersing essence function， so as to replenish the essential qi of zang-fu organs， ensure their distribution throughout the body， and improve the endocrine and exocrine functions of the pancreas.

Objective:To summarize the clinical characteristics and management experience of complications in patients with cervical necrotizing fasciitis （CNF） with or without descending necrotizing mediastinitis （DNM）, in order to provide a basis for optimizing diagnosis and treatment strategies. Methods:A retrospective analysis was conducted on the clinical data of 31 patients diagnosed with CNF and DNM at Shandong Provincial Hospital Affiliated to Shandong First Medical University between October 2019 and March 2024. A comprehensive evaluation was performed based on the patients' clinical characteristics, metagenomic next-generation sequencing （mNGS） pathogen detection results, imaging assessments, surgical interventions, management approaches for specific complications, and prognostic outcomes. Results:Among the 31 patients, 10 had severe diabetes mellitus. Etiological analysis was summarized as follows: 5 cases were odontogenic, 3 were of tonsillar origin, 3 were due to endogenous esophageal injury, 2 were due to exogenous cervical trauma, 2 originated from a congenital branchial cleft fistula, and 16 cases had an unknown etiology. Among them, 29 patients underwent surgery via an external cervical approach, 1 patient underwent surgery via an intraoral approach, and 1 patient received ultrasound-guided puncture and drainage therapy. Ultimately, 29 patients were cured and discharged （including 1 patient who experienced two instances of major neck vessel rupture and successfully underwent two interventional embolization procedures for hemostasis）; 2 patients died after failed rescue efforts due to concurrent sepsis and multiple organ dysfunction. The treatment success rate was 93%, and the mortality rate was 7%. In this cohort of CNF and DNM cases, only a minority had a clearly identified odontogenic cause; although the etiology was unknown in most cases, imaging consistently showed oropharyngeal lymph node necrosis, suggesting a possible pharyngeal origin of infection in adults. The mNGS pathogen profile was predominantly Gram-positive bacteria, accompanied by anaerobic bacilli and fungi. Conclusion:CNF and DNM are severe and rapidly progressive conditions that can lead to life-threatening complications within hours. Timely recognition can reduce unnecessary examinations and expedite treatment.
Humans ; Retrospective Studies ; Fasciitis, Necrotizing/therapy* ; Mediastinitis/complications* ; Neck/pathology* ; Male ; Female ; Middle Aged ; Adult ; Aged ; Prognosis

This study investigates the neuroprotective potential of extracellular vesicles (EVs) delivering quercetin-3-O-β-d-glucuronic acid (QG-EVs) in cerebral ischemia-reperfusion injury (CIRI). Targeted brain delivery of QG-EVs was confirmed, with neuron cells identified as pivotal in modulating CIRI through single-cell RNA sequencing (scRNA-seq). Activating transcription factor 4 (Atf4) was highlighted as a critical regulatory factor, and in vitro studies revealed that silencing Atf4 diminished the neuroprotective effects of QG-EVs, increasing oxidative stress levels and neuronal apoptosis. In a CIRI mouse model, the knockdown of Atf4 attenuated the protective outcomes provided by QG-EVs, further affirming the role of Atf4 in mediating neuroprotection. Behavioral assessments and protein analysis showed that QG-EVs significantly reduced neuronal damage and pro-apoptotic markers, while improving neurological function via Atf4 upregulation. The outcomes hint at the potential of QG-EVs as a beneficial therapeutic modality to mitigate neuronal damage in CIRI by enhancing Atf4 expression, highlighting its potential for improving ischemic stroke outcomes.

With the progress of society,the global development of scientific and technical research activities,and the increasing number of medical Institutional Review Board(IRB)review projects,the construction and management of electronic informatization have become extremely important.In the process of electronic information construction in institutional ethics review,it is necessary to take into account the new policy of ethical governance of science and technology,consider the system and standard operating procedures of IRB,and develop reasonable processes based on practical work,simplify manual operation,improve the accuracy of project management,achieve refined management,and facilitate communication among researchers,ethics committee secretaries,and members.

Objective:To analyze the protective effect of neurotracheal catheter monitoring on recurrent laryngeal nerve in patients with bilateral cervical lymph node dissection of thyroid cancer.Methods:The clinical data of 92 patients undergoing bilateral cervical lymph node dissection for thyroid cancer at the First People's Hospital of Shangqiu from Jul 2019 to Aug 2022 were retrospectively analyzed. Patients were divided into control group (routine exposure, 52 cases) and study group (intraoperative neurotrachatic catheter monitoring, 40 cases) The general data, perioperative indicators, parathyroid function, vocal cord function, voice disorder index, quality of life and postoperative complications were compared between the two groups.Results:The intraoperative blood loss in the study group [(12.3±3.3) ml] was less than that in the control group [(16.9±4.0) ml]. The exposure time [(8.7±2.6) min], operation time [(4.0±0.8) h] and postoperative hospitalization time [(3.2±0.9) d] were shorter than those of control group [(14.4±3.6) min, (4.5±1.2) h, (5.7±1.3) d] ( t=5.770, 8.391, 2.387, 10.853, all P<0.05);Amplitude perturbation (4.85%± 0.58%), fundamental frequency perturbation (0.28%±0.17%), standardized noise energy [(-20.3±4.4) dB], VHI-10 score [(1.6±0.5) score], Quality of life scale for cancer patients 1 month after surgery the TG-V4 score [(43.7±4.8) points] was lower than that of control group [(3.05%±0.54%), (0.42%±0.16%), (-14.6±3.3) dB, (3.3±0.4) points, (50.4±5.6) points]. The harmonic noise ratio [(24.9±4.1) dB] was higher than that of the control group [(20.3±4.4) dB] ( t=10.446, 4.049, 7.036, 19.076, 6.116, 5.144, all P<0.001);The incidence of postoperative complications in the study group (8%) was lower than that in the control group (23%) ( χ2=4.020, P=0.045). Conclusion:Neurotracheal catheter monitoring during bilateral cervical lymph node dissection for thyroid cancer can improve vocal cord function, reduce recurrent laryngeal nerve injury, reduce voice disturbance and improve quality of life.

ObjectiveTo investigate the induction of ferroptosis by polyphyllin Ⅱ （PPⅡ） in hepatocellular carcinoma HepG2 cells and its underlying mechanism. MethodThe effect of PPⅡ （0， 1.5， 3.0， 4.5， 6.0， 9.0， 18.0 mg·L^-1） on the in vitro proliferation of HepG2 cells was assessed using the methyl thiazolyl tetrazolium （MTT） assay. Colony formation ability of HepG2 cells was evaluated through a colony formation assay. Cell migration ability was assessed via a scratch assay. Lactate dehydrogenase （LDH） content in HepG2 cells was measured using a kit. Reactive oxygen species （ROS） levels in HepG2 cells were observed using a fluorescence inverted microscope. Malondialdehyde （MDA）， glutathione （GSH）， and free Fe²⁺ content in HepG2 cells were detected using respective kits. The mitochondrial ultrastructure in HepG2 cells was observed by transmission electron microscopy. The expression of ferroptosis-related proteins p53， solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， and transferrin receptor 1 （TFR1） in HepG2 cells was detected using Western blot. ResultCompared with the control group， the PPⅡ treatment groups showed significantly decreased survival rate of HepG2 cells in a dose-dependent manner （P<0.01）， significantly reduced number of cell colonies （P<0.01）， significantly shortened scratch healing distance， inverse correlation of the migration distance with drug concentration （P<0.01）， significantly increased LDH leakage in cells （P<0.01）， significantly enhanced relative fluorescence intensity of intracellular ROS， and significantly increased accumulation of lipid peroxide MDA （P<0.01）， decreased intracellular GSH content with increasing drug concentration （P<0.01）， and significantly enhanced fluorescence intensity of FeRhoNox-1 in cells （P<0.01）. Moreover， cells exhibited vacuolation， and mitochondria showed significant shrinkage with reduced or even disappeared cristae. Compared with the results in the control group， the expression of p53， ACSL4， and TFR1 proteins significantly increased， while the expression of SLC7A11 and GPX4 proteins significantly decreased in the PPⅡ treatment groups （P<0.05）. ConclusionIn summary， PPⅡ induces ferroptosis in HepG2 cells by regulating the p53/SLC7A11/GPX4 signaling axis， promoting ACSL4 expression and Fe³⁺ uptake， leading to an imbalance in the antioxidant system.

Currently,the ethical review model for organ donation and transplantation in domestic hospitals is generally characterized by suddenness,unpredictability,tight time,difficulty in convening meetings and training committee members,as well as generally low quality and efficiency of ethical review,which cannot meet clinical needs and cause the waste of some scarce resources.The team of the Clinical Application Center of Human Organ Transplantation and the Ethics Committee of the First People's Hospital of Kunming combine more than 10 years of review practice experience,as well as continuously explore and optimize the ethical review process and operating procedures for organ donation and transplantation.The special application has been approved and jointly developed with Soochow University and the Medical Ethics Committee of Fujian Province to build a full-process information software system management platform for organ ethical review of donation and transplantation,giving the full play the advantages of the review information system in improving work efficiency and review quality,facilitating full-process information management,and conducting online training and learning for committee members,with a view to providing a specialized practical model for addressing the difficulties and challenges related to ethical review of human organ donation and transplantation.

Objective: To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced (LPS-induced) depression mouse model. Methods: We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections. The mice were divided into the following groups: control, model, fluoxetine, Tiansi Yin, Sini powder, and low-, medium-, and high-dose Peiyuan Jieyu formula groups. Forced swim and tail suspension tests were used to assess the efficacy of the depression (despair) model, and weight gain rates were also measured. Furthermore, serum levels of various depression and inflammation-associated molecules, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), tryptophan, 5-hydroxytryptamine, kynurenine (KYN), and kynurenic acid (KA) were assessed. Furthermore, the expression levels of ionic calcium-binding adaptor molecule-1 (IBA-1) and indoleamine 2,3-dioxygenase (IDO) mRNA in hippocampal microglia were measured. Results: The model group displayed greater despair-associated immobility, which was shortened in response to various doses of Peiyuan Jieyu formula. Furthermore, formula administration significantly reduced serum TNF-α levels and hippocampal IDO mRNA expression. The high formula dose also reduced IFN-γ and IBA-1 levels, the latter was also decreased in response to the medium formula dose. However, the low formula dose reduced serum KYN level and KYN/tryptophan (TRP) and KYN/KA ratios. Conclusion The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model, potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.