Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of Paris polyphylla, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione (GSH) peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (Hic1), which binds to the Cx3cl1 promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective:To investigate the long-term efficacy, safety and prognostic factors of intraoperative radiotherapy (IORT) for narrow-margin (resection margin < 1 cm) hepatectomy in patients with hepatocellular carcinoma (HCC) during radical surgery.Methods:A retrospective cohort study was conducted. The data of primary HCC patients undergoing radical surgery and narrow-margin hepatectomy IORT in the Cancer Hospital of the Chinese Academy of Medical Sciences from November 2009 to February 2019 were collected. IORT applied 6 MeV or 9 MeV electron beams and a single irradiation was given to the margin. Kaplan-Meier method was used for the overall survival (OS) and disease-free survival (DFS) analysis; log-rank test was used for survival comparison among subgroups. The recurrence patterns and adverse reactions were recorded. Univariate and multivariate Cox proportional hazards models were used to analyze the factors influencing the OS and DFS.Results:A total of 64 patients were enrolled, with the median age [ M ( Q1, Q3)] of 57 years (49, 63) years. All patients included 55 males (85.9%) and 9 females (14.1%). The median dose of IORT was 15 Gy (range: 12-17 Gy). The median follow-up time was 83.3 (64.4, 91.9) months. The 1-year, 3-year, 5-year, 7-year, 10-year OS rates were 90.4%, 80.6%, 75.5%, 71.4% and 47.6%, respectively; the 1-year, 3-year, 5-year, 7-year,10-year DFS rates were 77.8%, 68.1%, 59.6%, 57.6% and 38.4%, respectively. Univariate Cox regression analysis indicated that preoperative serum alpha-fetoprotein (AFP) > 400 ng/ml was an independent risk factor for poor OS (> 400 ng/ml vs. ≤ 400 ng/ml: HR = 6.57, 95% CI: 2.16-19.96, P < 0.001), while not the independent influencing factor of poor DFS ( HR = 1.71, 95% CI: 0.65-4.52, P = 0.277). The age ≤ 60 years or not, gender, viral hepatitis or not, American Joint Committee on Cancer stage, tumor diameter (> 5 cm or not), tumor number, degree of tumor differentiation, microvascular invasion or not, microsatellite nodules or not, anatomical liver resection or not, and the dose of IORT ≤15 Gy or not were not the independent influencing factors of poor OS and DFS (all P > 0.05). Kaplan-Meier method analysis showed that patients with preoperative serum AFP ≤ 400 ng/ml (48 cases) had better OS compared with those with preoperative serum AFP>400 ng/ml (16 cases) (5-year OS rate: 84.8% vs. 44.9%; 7-year OS rate: 79.9% vs.37.4%), and the difference was statistically significant ( P = 0.002). There was no statistically significant difference in the DFS between the 2 groups ( P = 0.134). During the follow-up, 28 patients (43.8%) relapsed, including 17 cases (26.6%) of early recurrence and 11 cases (17.2%) of late recurrence. No marginal recurrence was observed. There were 22 cases (34.4%) of intrahepatic recurrence alone, 2 cases (3.1%) of extrahepatic recurrence and 4 cases (6.3%) of stimutaneous recurrence inside and outside the liver. The 1-, 3-, 5- and 7-year cumulative recurrence rates inside the liver were 19.0%, 27.2%, 37.4% and 39.3% respectively, and the cumulative recurrence rates outside the liver were 6.4%, 8.0%, 9.6% and 9.6% respectively. There were no adverse reactions above grade 3 in the entire group. There were no surgery-related deaths within 30 d after the operation, and no radiation-induced liver disease occurred. Conclusions:Narrow-margin IORT helps HCC patients receiving hepatectomy to achieve favorable long-term survival and adverse reactions are tolerable. It can be used as a safe and effective adjuvant therapy alternative.

Lung cancer (LC) complicated with interstitial lung disease (ILD) is a relatively common comorbidity in clinical practice, and its management remains complex and challenging. As one of the primary treatment modalities for LC, radiotherapy carries a risk of inducing acute exacerbation of ILD and severe radiation pneumonitis; therefore, it should be used with caution in LC-ILD patients. Advances in radiotherapy technology now allow for more precise tumor targeting and better sparing of healthy lung tissues, potentially offering greater therapeutic benefits for these patients. In this article, current status and recent research progress in the application of radiotherapy in LC-ILD were reviewed, aiming to provide theoretical basis and reference for clinical practice.

Objective:To investigate the intervention effect of five elements music of traditional Chinese medicine and western classical music on the sleep quality of stroke patients, and to compare the difference between the two, to provide a reference for the clinical care measures to improve the sleep quality of stroke patients.Methods:By adopting a randomized controlled trial, 75 stroke patients who were hospitalized in the rehabilitation hospital of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from July 2022 to July 2023 were selected by convenience sampling method as the study subjects, and the patients were randomly divided the conventional treatment group, the five-element music group, and the classical music group according to the method of randomized numerical table with 25 cases in each group. On the basis of general treatment, the conventional treatment group took sleep health education, the five elements music group were given five-element music intervention based on conventional treatment, and the classical music group were given classical music intervention based on conventional treatment. The changes of Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) examination parameters in the 3 groups were compared.Results:There were 2 cases of shedding in the conventional treatment group, and 23 cases were finally included, 15 males and 8 females, aged (54.02 ± 7.80) years; there were no cases of shedding in the five-element music group, and 25 cases were finally included, 12 males and 13 females, aged (53.69 ± 6.02) years; and there was 1 case of shedding in the classical music group, and 24 cases were finally included, 10 males and 14 females, aged (52.34 ± 7.08) years. Comparison of AIS, PSQI and PSG scores among the 3 groups of patients before intervention showed no statistically significant differences (all P>0.05). After the intervention, the AIS scores and PSQI scores of the 3 groups were (9.48 ± 1.53) and (12.22 ± 2.94), (6.76 ± 1.36) and (7.64 ± 2.08), (7.46 ± 1.38) and (10.33 ± 2.82), respectively, and the differences were statistically significant ( F=23.21, 18.44, both P<0.05). PSG sleep structure parameters showed that the total sleep time, REM latency time and sleep efficiency of the patients in the five-element music group after the intervention were (399.89 ± 51.76) min, (136.26 ± 25.36) min, (78.87 ± 8.21)%, higher than (368.45 ± 47.88) min, (124.46 ± 26.25) min, (73.36 ± 7.86)% in the classical music group and (345.48 ± 38.69) min, (111.37 ± 23.23) min, (69.44 ± 7.88)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=8.27, 5.93, and 8.49, all P<0.05); the sleep latency time, awakening time, and number of awakenings in the five-element music group were (28.86 ± 17.68) min, (54.37 ± 25.15) min, and (2.72 ± 1.19) times, respectively, which were lower than those in the classical music group (35.67 ± 16.99) min, (64.28 ± 29.34) min, and (3.67 ± 1.12) times and (42.38 ± 18.96) min, (78.38 ± 37.26) min, (4.87 ± 1.46) times in the conventional treatment group, and the differences between three groups were statistically significant ( F=3.51, 3.66, and 17.56, all P<0.05). The results of the PSG sleep progression showed that the duration of the N1 stage of sleep in the five-element music group after the intervention was (95.71 ± 15.23) min, which was higher than (83.20 ± 18.34) min in the classical music group and (80.93 ± 16.47) min in the conventional treatment group, and the difference between three groups was statistically significant ( F=5.53, P<0.01); the N3 stage sleep time and the sleep percentage of the five-element music group after the intervention were respectively (84.23 ± 20.98) min and (23.98 ± 5.89)%, which were higher than (65.33 ± 18.82) min and (18.34 ± 3.78)% in the classical music group and (45.87 ± 18.65) min and (15.03 ± 5.56)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=23.08, 18.50, both P<0.05). Conclusions:Both five elements music and classical music can improve the sleep quality of stroke patients, and the effect of five elements music to improve sleep is more significant.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Ferroptosis has been shown to mediate the development of fibrosis.Polyphyllin Ⅶ(PP7),a bioactive component of Paris polyphylla,exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis.In this study,treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells(HSCs),which could be suppressed by a ferroptosis inhibitor.In addition,it promoted HSC ferroptosis by suppressing glutathione(GSH)peroxidase 4(GPX4)and enhanced the expression of CX3C chemokine ligand 1(CX3CL1).Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4.Notably,CX3CL1 directly interacted with GPX4,triggering HSC ferroptosis.The transcription factor hypermethylated in cancer 1(Hic1),which binds to the Cx3cl1 promoter,increased the expression of CX3CL1.Its absence resulted in downregulation of CX3CL1,sup-pressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation.HIC1 was found to directly interact with PP7 at the GLY164 site.Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes.HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo.These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

Cerebral autoregulation(CA)refers to the ability of cerebral blood vessels to maintain stable cerebral hemodynamics in response to changes in factors such as carbon dioxide concentration,mean arterial pressure,or cerebral perfusion pressure.Acute ischemic stroke has a high incidence,disability rate,and mortality rate.Previous studies have confirmed varying degrees of impairment in CA among patients with acute ischemic stroke after the onset of the disease,but the specific mechanisms remain not fully understood.This article reviewed the mechanisms of CA,assessment methods,and its application progress in acute ischemic stroke,with the intention of providing references for related research and clinical diagnosis and treatment.

Human immunodeficiency virus(HIV)is the pathogen of acquired immune deficiency syndrome(AIDS).The vi-rus is a highly contagious and highly pathogenic disease caused by the virus attacking the human immune system,which remains a ma-jor global public health problem.Interferon(IFN)is a key cytokine with antiviral and cell-regulatory properties,involved in functions such as cell proliferation,innate and adaptive immune responses.The JAK/STAT signaling pathway is a signal transduction pathway stimulated by cytokines that is involved in many important biological processes such as cell proliferation,differentiation,apoptosis,and immune regulation.With the further in-depth research on AIDS,it has been revealed that IFN and the JAK/STAT pathway play crucial roles in the activation and replication of HIV-1 in target cells.This paper summarizes the structure,signal transduction,and regulatory mechanisms of IFN and the JAK/STAT pathway,and explores the mechanism of IFN-regulated JAK/STAT signaling path-way in HIV-1.It is expected to provide new treatment strategies for the clinical treatment of AIDS.

Objective:To investigate the intervention effect of five elements music of traditional Chinese medicine and western classical music on the sleep quality of stroke patients, and to compare the difference between the two, to provide a reference for the clinical care measures to improve the sleep quality of stroke patients.Methods:By adopting a randomized controlled trial, 75 stroke patients who were hospitalized in the rehabilitation hospital of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from July 2022 to July 2023 were selected by convenience sampling method as the study subjects, and the patients were randomly divided the conventional treatment group, the five-element music group, and the classical music group according to the method of randomized numerical table with 25 cases in each group. On the basis of general treatment, the conventional treatment group took sleep health education, the five elements music group were given five-element music intervention based on conventional treatment, and the classical music group were given classical music intervention based on conventional treatment. The changes of Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) examination parameters in the 3 groups were compared.Results:There were 2 cases of shedding in the conventional treatment group, and 23 cases were finally included, 15 males and 8 females, aged (54.02 ± 7.80) years; there were no cases of shedding in the five-element music group, and 25 cases were finally included, 12 males and 13 females, aged (53.69 ± 6.02) years; and there was 1 case of shedding in the classical music group, and 24 cases were finally included, 10 males and 14 females, aged (52.34 ± 7.08) years. Comparison of AIS, PSQI and PSG scores among the 3 groups of patients before intervention showed no statistically significant differences (all P>0.05). After the intervention, the AIS scores and PSQI scores of the 3 groups were (9.48 ± 1.53) and (12.22 ± 2.94), (6.76 ± 1.36) and (7.64 ± 2.08), (7.46 ± 1.38) and (10.33 ± 2.82), respectively, and the differences were statistically significant ( F=23.21, 18.44, both P<0.05). PSG sleep structure parameters showed that the total sleep time, REM latency time and sleep efficiency of the patients in the five-element music group after the intervention were (399.89 ± 51.76) min, (136.26 ± 25.36) min, (78.87 ± 8.21)%, higher than (368.45 ± 47.88) min, (124.46 ± 26.25) min, (73.36 ± 7.86)% in the classical music group and (345.48 ± 38.69) min, (111.37 ± 23.23) min, (69.44 ± 7.88)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=8.27, 5.93, and 8.49, all P<0.05); the sleep latency time, awakening time, and number of awakenings in the five-element music group were (28.86 ± 17.68) min, (54.37 ± 25.15) min, and (2.72 ± 1.19) times, respectively, which were lower than those in the classical music group (35.67 ± 16.99) min, (64.28 ± 29.34) min, and (3.67 ± 1.12) times and (42.38 ± 18.96) min, (78.38 ± 37.26) min, (4.87 ± 1.46) times in the conventional treatment group, and the differences between three groups were statistically significant ( F=3.51, 3.66, and 17.56, all P<0.05). The results of the PSG sleep progression showed that the duration of the N1 stage of sleep in the five-element music group after the intervention was (95.71 ± 15.23) min, which was higher than (83.20 ± 18.34) min in the classical music group and (80.93 ± 16.47) min in the conventional treatment group, and the difference between three groups was statistically significant ( F=5.53, P<0.01); the N3 stage sleep time and the sleep percentage of the five-element music group after the intervention were respectively (84.23 ± 20.98) min and (23.98 ± 5.89)%, which were higher than (65.33 ± 18.82) min and (18.34 ± 3.78)% in the classical music group and (45.87 ± 18.65) min and (15.03 ± 5.56)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=23.08, 18.50, both P<0.05). Conclusions:Both five elements music and classical music can improve the sleep quality of stroke patients, and the effect of five elements music to improve sleep is more significant.