Aim To investigate the radio-protective effect of schisandrol B(Sol B)underlying mechanism in alleviating gastrointestinal(GI)toxicity and intesti-nal damage induced by irradiation(IR)exposure dur-ing radiotherapy against abdominal and pelvic malig-nancies or the nuclear accident.Methods The mouse intestinal injury model was established through 4Gy ir-radiation.Immunohistochemistry,immunofluorescence staining,ELISA were used to measure DNA damage,apoptosis,inflammatory reaction,and oxidative stress in the intestine of mice after irradiation.The protective effect of Sol B on intestines injury was evaluated,and the mechanism of the related oxidative stress and in-flammatory response pathway was discussed.Results Sol B significantly improved the survival rates of intes-tinal cells upon IR exposure.The accumulation of DNA damage,apoptosis rate,and inflammatory factors in intestinal tissues were significantly inhibited.The decreased levels of ZO-1 and occludin induced IR inju-ry were rescued by Sol B,indicating the improvement of intestinal structure.The radio-protective activities of Sol B were involved in the stimulation of Nrf2 and the subsequent ferroptosis surveillance.Conclusion Sol B demonstrates a promising agent to ease intestinal in-jury during radiotherapy or nuclear accidents,in which GPX4 related ferroptosis surveillance mediated by Nrf2 is involved in the radio-protective effect of Sol B.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective:To assess the deformation of the bladder-neck opening and the impact of the bladder-neck angle(BNA)on urination in male patients by fluid-structure interaction(FSI)analysis.Methods:We established geometric models of the blad-der,prostate and urethra were established,incorporating both normal and enlarged BNAs,and assessed the effects of BNA alteration on urinary flow by FSI simulation of the flow rate and pressure of the urine within the bladder,bladder neck and urethra,and that of pros-tate displacement as well.We retrospectively analyzed the clinical data on 145 male patients from the Second Hospital of Hebei Medical University between June 2020 and June 2023,39 with acute urine retention(the AUR group)and 106 without(the non-AUR group),and evaluate the impact of BNA on urination based on the urinary flow rate and prostate volume.Results:Comparative simulation a-nalysis showed significant differences in the total urethral pressure and flow rate between the normal and enlarged BNA models(P＜0.05).The maximum prostate displacement was found at the bladder neck,with moderate displacement and unchanged urethral diame-ter in the normal BNA model,but significant displacement and a reduced urethral opening diameter in the enlarged BNA model.FSI analysis confirmed an evident impact of enlarged BNA on urination,more significant in the AUR than in the non-AUR patients(P＜0.05).The BNAs in the patients with the maximum urinary flow rate(Qmax)of＜10,10-15 or＞15 ml/s were 83.7°±2.5°,67.5°±1.8° and 65.1°±4.8° respectively,with statistically significant difference between the former one and the latter two groups(P＜0.05).The BNAs in the patients with normal prostate volume or BPH of grade Ⅰ,Ⅱ,Ⅲ or Ⅳ were 65.0°±3.7°,67.2°±3.1°,71.5°±2.0°,82.8°±3.5° and 105.8°±6.0°,respectively(P＜0.05),with statistically significant difference between BPH grades Ⅲ and Ⅳ(P＜0.05)as well as between these two and the other three groups(P＜0.05),but not among the normal prostate volume,BPH grade Ⅰ and BPH grade Ⅱ groups(P＞0.05).Spearman correlation analysis indicated that BNA was strongly correlated with total prostate volume(TPV),transition zone volume(TZV),intravesical prostatic protrusion(IPP),prostatic urethral angle(PUA),IPSS,and Qmax(P＜0.05).Conclusion:Changes in BNA affect urination and are closely associated with the se-verity of prostate hyperplasia.The BNA may be an important anatomical factor for assessing the severity of lower urinary tract symptoms in BPH patients.

Pulmonary arterial hypertension(PAH)is a severe disease characterized by abnormal pulmonary vascular remodeling and increased right ventricular pressure load,posing a significant threat to patient health.While some pathological mechanisms of PAH have been revealed,the deeper mechanisms of pathogenesis remain to be elucidated.In recent years,bioinformatics has provided a powerful tool for a deeper understanding of the complex mechanisms of PAH through the integration of techniques such as multi-omics analysis,artificial intelligence,and Mendelian randomization.This review focuses on the bioinformatics methods and technologies used in PAH research,summarizing their current applications in the study of disease mechanisms,diagnosis,and prognosis assessment.Additionally,it analyzes the existing challenges faced by bioinformatics and its potential applications in the clinical and basic research fields of PAH in the future.[Chinese Journal of Contemporary Pediatrics,2024,26(4):425-431]

Aim To investigate the protective effect of dimethyl fumarate on spleen injury induced by gamma radiation in mice and the related mechanism. Methods C57BL/6 mice were randomly divided into the blank control group, radiation model group and DMF administration group, which were administered once at 12 h before irradiation and once at 0. 5 h, 12 h, 24 h and 48 h after irradiation. The 30-day survival rate, body weight and pathological injury of spleen were measured after a one-time total body irradiation of Co 7 rays (8 Gy). TUNEL staining was used to detect apoptosis of spleen cells. Enzyme-linked immunoassay ( ELISA) was applied to detect the contents of TNF-a, IL-1 p, IL-6, IL-18, NLRP3 and AIM2 in spleen. Western blot test and immunofluorescence staining test was employed to verify the changes of NLRP3 and AIM2 contents in spleen tissue after irradiation. Results DMF could obviously improve the survival rate of irradiated mice, improve the weight loss of irradiated mice, re-duce the pathological injury of spleen, and inhibit the apoptosis of spleen cells after irradiation. ELISA results showed that DMF could significantly inhibit the increase of spleen inflammatory cytokines TNF-a, IL-lp, IL-6, IL-18 and inflammasome components NL-RP3 and AIM2 induced by irradiation. Western blot and tissue immunofluorescence staining also confirmed that DMF could inhibit the increase of NLRP3 and AIM2 inflammasome protein levels caused by irradiation. Meanwhile, NLRP3 agonist and AIM2 agonist could antagonize the radiation protection effect of DMF on spleen cells. Conclusion DMF can ameliorate spleen injury of Co 7-ray injured mice, and its mechanism is closely related to NLRP3/AIM2 inflamma-somes, which can be used as a potential protective drug for radiation injury.

OBJECTIVE: AP2/ERF (APETALA2/ethylene-responsive factor) superfamily is one of the largest gene families in plants and has been reported to participate in various biological processes, such as the regulation of biosynthesis of active lignan. However, few studies have investigated the genome-wide role of the AP2/ERF superfamily in Isatis indigotica. This study establishes a complete picture of the AP2/ERF superfamily in I. indigotica and contributes valuable information for further functional characterization of IiAP2/ERF genes and supports further metabolic engineering. METHODS: To identify the IiAP2/ERF superfamily genes, the AP2/ERF sequences from Arabidopsis thaliana and Brassica rapa were used as query sequences in the basic local alignment search tool. Bioinformatic analyses were conducted to investigate the protein structure, motif composition, chromosome location, phylogenetic relationship, and interaction network of the IiAP2/ERF superfamily genes. The accuracy of omics data was verified by quantitative polymerase chain reaction and heatmap analyses. RESULTS: One hundred and twenty-six putative IiAP2/ERF genes in total were identified from the I. indigotica genome database in this study. By sequence alignment and phylogenetic analysis, the IiAP2/ERF genes were classified into 5 groups including AP2, ERF, DREB (dehydration-responsive element-binding factor), Soloist and RAV (related to abscisic acid insensitive 3/viviparous 1) subfamilies. Among which, 122 members were unevenly distributed across seven chromosomes. Sequence alignment showed that I. indigotica and A. thaliana had 30 pairs of orthologous genes, and we constructed their interaction network. The comprehensive analysis of gene expression pattern in different tissues suggested that these genes may play a significant role in organ growth and development of I. indigotica. Members that may regulate lignan biosynthesis in roots were also preliminarily identified. Ribonucleic acid sequencing analysis revealed that the expression of 76 IiAP2/ERF genes were up- or down-regulated under salt or drought treatment, among which, 33 IiAP2/ERF genes were regulated by both stresses. CONCLUSION This study undertook a genome-wide characterization of the AP2/ERF superfamily in I. indigotica, providing valuable information for further functional characterization of IiAP2/ERF genes and discovery of genetic targets for metabolic engineering.
Abscisic Acid ; Isatis/genetics* ; Multigene Family ; Phylogeny ; Homeodomain Proteins/genetics* ; Genome, Plant

【Subjects】 To investigate the clinical application value of myocardial contrast echocardiography （MCE） in selecting CTO-PCI patients. MethodsFrom February 2019 to March 2020， a total of 50 patients with chronic coronary artery occlusion were consecutively selected as the research subjects. MCE and two-dimensional speck-tracking echocardiography were completed before and 12 months after interventional therapy. The primary end point was major adverse cardiovascular events. Patients were divided into groups according to the preoperative myocardial perfusion level of MCE. The improvement of left ventricular function was evaluated by two-dimensional echocardiography and left ventricular global longitudinal strain. ResultsCompared with the abnormal perfusion group， the improvement of GLS in the normal perfusion group was greater （P=0.028）. The wall motion score index （WMSI） of the abnormal perfusion group before PCI was higher than that of the normal perfusion group （P=0.002）. WMSI in the abnormal perfusion group was higher than that in the normal perfusion group one year after PCI （P<0.001）. The left ventricular GLS（P=0.008）.WMSI（P=0.016） and left ventricular end-diastolic volume（P=0.032） in the normal perfusion group were improved compared with those before operation； The postoperative perfusion score of patients with abnormal perfusion was significantly improved （ P=0.032）. ConclusionMCE has clinical application value in optimizing the selection of CTO-PCI patients. CTO patients with different myocardial perfusion types have different benefits after PCI.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.
Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Facial Paralysis/etiology* ; Diagnosis, Differential ; Jugular Foramina ; Retrospective Studies ; Cough ; Hoarseness ; Neoplasm Recurrence, Local ; Chondrosarcoma/surgery*