1.Phosphatidylethanolamine promotes macrophage senescence and liver injury by activating endoplasmic reticulum stress
Longchuan HAN ; Yue LI ; Zhihui ZOU ; Jing LUO ; Ruoyi LI ; Yingting ZHANG ; Xinxin TANG ; Lihong TIAN ; Yuheng LU ; Ying HUANG ; Ming HE ; Yinkun FU
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(6):693-704
Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.
2.Preparation of polyvinyl butyral nanofiber membrane loaded with propolis and its property
Zhihui DAI ; Yungang LUO ; Zhihui LIU
Journal of Jilin University(Medicine Edition) 2025;51(1):238-244
Objective:To prepare a polyvinyl butyral(PVB)nanofiber membrane loaded with propolis,and to clarify its physicochemical properties,drug release behavior,antibacterial activity,and biocompatibility.Methods:Propolis with a mass fraction of 0.12%was dissolved in 18%(mass fraction)PVB methanol solution.PVB and PVB-propolis(PVB-P)nanofiber membranes were prepared using electrospinning from PVB and PVB-P solutions,respectively.Scanning electron microscope(SEM)was used to observe the microscopic morphology of PVB-P nanofibers,and the Nano Measurer software was used to analyze the fiber diameter distribution.Fourier transform infrared spectroscopy(FTIR)was used to analyze the chemical composition of PVB-P.Water contact angle measurements were used to evaluate the hydrophilicity of PVB-P.UV spectrophotometer was used to detect the cumulative release of propolis at different time points.PVB and PVB-P nanofiber membranes were co-cultured with Staphylococcus aureus(S.aureus),Escherichia coli(E.coli),Candida albicans(C.albicans),Salmonella,and Pseudomonas aeruginosa(P.aeruginosa)and divided into PVB group and PVB-P group.The absorbance method was used to calculate the antibacterial values of PVB and PVB-P against the five types of bacteria.The NIH-3T3 cells were seeded on PVB and PVB-P nanofiber membranes and divided into PVB group and PVB-P group.The CCK-8 method was used to detect the survival rates of NIH-3T3 cells on the nanofiber membranes in PVB group and PVB-P group at 1,3,and 7 d.Results:The SEM results showed that PVB and PVB-P nanofibers were interconnected in a mesh-like porous structure,with uniform thickness and no beads.The Nano Measurer software measurement results showed that the diameter of PVB nanofibers was(0.50±0.10)μm,and the diameter of PVB-P nanofibers was(0.54±0.16)μm.FTIR analysis showed that PVB-P nanofiber membranes exhibited characteristic peaks of PVB(1 140 and 1 002 cm-1)and propolis(1 161 cm-1).The water contact angle measurement results showed that the contact angle of PVB membrane was(144.26°±2.90°)and that of PVB-P membrane was(128.13°±1.36°).The UV spectrophotometer results showed that the cumulative release of propolis was 0.04 mg at 1d,0.07 mg at 3 d,and reached a steady state of 0.79 mg at 7 d.The absorbance method results showed that the antibacterial values of PVB-P nanofiber membranes against S.aureus,E.coli,C.albicans,Salmonella,and P.aeruginosa were 4.39,1.27,5.68,3.16,and 1.87,respectively.The CCK-8 method results showed that the survival rates of NIH-3T3 cells on PVB and PVB-P nanofiber membranes was>90%at 1,3,and 7 d,and there were no significant differences between various groups(P>0.05).Conclusion:The diameter of PVB nanofiber membranes loaded with propolis is increased,and these membranes exhibit antibacterial effects against S.aureus and C.albicans,while also achieving sustained release of propolis.
3.Dicentrine inhibits lipopolysaccharide-induced inflammatory response by modulating apoptosis in RAW264.7 cells
Zhihui LUO ; Zhengtang SUN ; Wenju LI ; Zhiqiang TANG
Chongqing Medicine 2025;54(11):2538-2543
Objective To investigate the role of Dicentrine in regulating lipopolysaccharide(LPS)-induced inflammatory responses in RAW264.7 macrophages and its underlying mechanisms.Methods RAW264.7 macropha-ges were cultured and pretreated with different concentrations of Dicentrine(250,500,1 000 μmol/L).An inflam-matory response model was established using LPS stimulation(model group),with a control group receiving no treatment.Cytotoxicity of Dicentrine was evaluated by MTT assay.Nitric oxide(NO)levels in cell culture supernatants were measured using the Griess method.Fluorescence microscopy was employed to observe in-tracellular reactive oxygen species(ROS)accumulation and apoptosis.Finally,mRNA expression levels of in-flammatory cytokines including IL-1β,IL-6,inducible nitric oxide synthase(iNOS),and tumor necrosis factor-α(TNF-α)were analyzed by qPCR.Results MTT assay results indicated that Dicentrine exhibited no cyto-toxic effects at concentrations below 1 000 μmol/L.Griess method and fluorescence microscopy showed signif-icantly elevated NO and ROS levels in the model group compared to the control group(P<0.05).Compared with the model group,the 250,500,and 1 000 μmol/L Dicentrine groups demonstrated significantly reduced NO and ROS levels(P<0.05).qPCR analysis revealed significantly increased mRNA expression of IL-1β,IL-6,iNOS,and TNF-α in the model group versus the control group(P<0.05).Compared with the model group,the 250,500,and 1 000 μmol/L Dicentrine groups showed significantly decreased mRNA expression of IL-1β,IL-6,iNOS,and TNF-α(P<0.05).Conclusion Dicentrine regulates macrophage apoptosis,thereby ef-fectively inhibiting LPS-induced inflammatory responses in macrophages.
4.Practice of individual scientific research performance evaluation for medical staff in tertiary public hospitals under the background of breaking the " five only" evaluation criteria
Fei LUO ; Zhigang LIU ; Yuefang JIAO ; Yingcong ZHANG ; Zhihui WANG ; Qingsong WU ; Zibing WANG ; Zheng WANG ; Qiang YAO ; Yang JIN
Chinese Journal of Hospital Administration 2025;41(2):127-132
Under the background of breaking the " five only" evaluation criteria, continuously optimizing the scientific research performance evaluation system of hospitals to mobilize the enthusiasm and creativity of scientific researchers and guide the direction of scientific research development plays an important role in enhancing the overall scientific research capability of hospitals. Through literature analysis and expert consultation, a certain hospital has constructed a personal scientific research performance evaluation index system for medical staff in tertiary public hospitals, oriented towards innovation quality and member contributions, and began to implement it throughout the hospital in 2021. This index system included four categories of scientific research performance: vertical scientific research projects, academic influence, science and technology awards, and transformation of achievements, with a total of 20 indicators. The annual scientific research performance score of an individual would serve as the basis for the distribution of year-end scientific research performance and an important reference for applying for key and major projects within the hospital. After the application of this evaluation index system, the enthusiasm of medical staff for scientific research has been effectively stimulated. The average individual scientific research performance score increased from 0.974 in 2020 to 1.220 in 2023. All scientific research indicators involved in the evaluation system have shown growth, with a significant increase in high-quality results. This evaluation system can provide a reference for the scientific research performance evaluation of public hospitals under the background of breaking the " five only" evaluation criteria.
5.Total 3D laparoscopic ileal ureters replacement for bilateral ureters combined with bladder augmentation in the management of post-radiotherapy bilateral ureteral strictures and contracted bladder
Wanwei HUANG ; Xianshen SHA ; Yibao ZHANG ; Guohao WU ; Feng LUO ; Zhihui CHEN ; Dongming YE ; Xue-song LI ; Caiyong LAI
Journal of Peking University(Health Sciences) 2025;57(4):789-795
Objective:To retrospectively evaluate the clinical efficacy and safety of total 3D laparo-scopic ileal ureters replacement for bilateral ureters combined with bladder augmentation in patients with post-radiotherapy long-segment bilateral ureteral strictures and contracted bladder.Methods:Clinical data of two patients(aged 72 and 54 years)with radiation-induced long-segment bilateral ureteral stric-tures and reduced bladder capacity,treated at the Sixth Affiliated Hospital of Jinan University from Octo-ber 2023 to June 2024,were analyzed.Both presented with bilateral flank pain,recurrent chills/fever,urinary frequency,and urgency.Preoperative ureteral stricture lengths were measured as follows:left 10.4 cm and right 8.7 cm in the first case;left 10.6 cm and right 11.7 cm in the second case.Bladder capacity assessed by nephrostomy-assisted antegrade urography was 90 mL and 130 mL respectively.Both underwent single-position,one-stage totally 3D laparoscopic bilateral ileal ureteral replacement and blad-der augmentation based on membrane anatomy principles,with regular postoperative follow-up.Results:Procedures were completed by the same experienced urologist.Operative times were 420 min and 355 min,with intraoperative blood loss of 50 mL(no transfusion required).Postoperative bowel function re-sumed at the end of 4.5 and 3 days.No major perioperative complications occurred.Ureteral stents were removed at 2 months postoperatively,with imaging showing improved hydronephrosis,unobstructed ure-teral drainage,symmetrical bladder morphology,and smooth walls.Postoperative bladder capacities were 230 mL and 250 mL.Follow-up durations were 10 and 8 months.Both patients experienced significant relief of flank pain and lower urinary tract symptoms.No complications(enteric fistula,urinary fistula,or metabolic acidosis)were observed.At the final follow-up,one patient had mildly elevated serum cre-atinine,while the other showed reduced levels compared with preoperative values;both remained stable.Conclusion:Membrane anatomy-based dissection facilitates safe mobilization of fibrotic ureters with mini-mal bleeding and collateral damage.Total intracorporeal 3D laparoscopic ileal ureters replacement for bi-lateral ureters combined with bladder augmentation effectively addresses long-segment ureteral obstruction and improves bladder capacity.This approach is technically safe and feasible,though further validation with larger clinical cohorts is warranted.
6.Correlations of Fib/Alb,sTLT-1 and NGAL in peripheral blood at admission with risk of poor prognosis in patients with acute thoracoabdominal trauma and their early warning values
Jucheng LIN ; Shigui LUO ; Qilun HE ; Zhihui HENG ; Shiguo WANG
Journal of Clinical Medicine in Practice 2025;29(18):91-96,116
Objective To investigate the correlations of fibrinogen-to-albumin ratio(Fib/Alb),soluble myeloid cell triggering receptor-like transcript factor-1(sTLT-1)and neutrophil gelatinase-as-sociated lipocalin(NGAL)in peripheral blood at admission with the risk of poor prognosis in patients with acute thoracoabdominal trauma and their early warning values.Methods A prospective study was conducted in 152 patients with acute thoracoabdominal trauma in the hospital from January 2022 to May 2024.The patients were divided into good prognosis group(n=120)and poor prognosis group(n=32)according to their prognosis.Baseline data and the levels of Fib/Alb,sTLT-1 and NGAL in peripheral blood at admission were compared between the two groups.The relationships between the levels of Fib/Alb,sTLT-1,and NGAL in peripheral blood at admission and the severity of trauma[the Circulation,Respiration,Abdomen,Movement,and Speech(CRAMS)score]and the risk of poor prognosis were analyzed.The early warning values of the levels of Fib/Alb,sTLT-1 and NGAL in peripheral blood at admission for the risk of poor prognosis were evaluated.Results The time from injury to admission in the poor prognosis group was longer than that in the good prognosis group,the CRAMS score,the Glasgow Coma Scale(GCS)score,and the levels of Fib,Alb and Fib/Alb in peripheral blood at admission in the poor prognosis group were lower than those in the good prognosis group,while the Sequential Organ Failure Assessment(SOFA)score and the levels of sTLT-1 and NGAL in peripheral blood at admission were higher than those in the good prognosis group,with statistically significant between-group differences(P<0.05).The levels of Fib,Alb and Fib/Alb in peripheral blood at admission showed a decreasing trend,while the levels of sTLT-1 and NGAL showed an increasing trend in patients with mild,severe,and extremely severe trauma,with statistically significant differences(P<0.05).Pearson correlation analysis showed that the level of Fib/Alb in peripheral blood at admission(r=0.839)was positively correlated with the CRAMS score,while the levels of sTLT-1 and NGAL(r=-0.832,-0.808)were negatively cor-related with the CRAMS score(P<0.05).Logistic regression analysis showed that after adjusting for confounding factors,the levels of Fib/Alb(OR=0.769),sTLT-1(OR=1.562)and NGAL(OR=1.575)in peripheral blood at admission were still independently correlated with the risk of poor prognosis(P<0.05).The receiver operating characteristic(ROC)curve showed that the area under the curve(AUC)for the combined early warning of the risk of poor prognosis by the levels of Fib/Alb,sTLT-1,and NGAL in peripheral blood at admission was 0.918,which was superior to the early warning value of individual indicators(Z=2.992,2.291,2.082,P<0.05).Conclusion The levels of Fib/Alb,sTLT-1 and NGAL in peripheral blood are closely related to the severity of trauma and prognosis in patients with acute thoracoabdominal trauma.Combined detection has a certain ear-ly warning value for the risk of poor prognosis and can be used as potential factors for clinical assess-ment of trauma condition and early warning of the risk of poor prognosis.
7.Research Progress on Targeted Therapy and Resistance Mechanisms of Malignant Melanoma
Yifan LIU ; Xing LUO ; Tianci SONG ; Zhihui YANG
Journal of Kunming Medical University 2025;46(2):158-163
Malignant melanoma is an extremely aggressive tumor that can be surgically treated in its early stage.In advanced stages,the invasive and proliferative capabilities of melanoma cells continue to increase,and traditional treatment methods such as radiotherapy,chemotherapy,and immunotherapy have limited efficacy,resulting in poor patient prognosis.Due to the presence of mutations in multiple molecular pathways in malignant melanoma,targeted therapy is now regarded as a more viable treatment option for patients with advanced malignant melanoma,with most patients benefiting from it.However,the development of drug resistance to targeted therapy has always been a serious challenge,as the emergence of resistance limits the efficacy.Therefore,it is necessary to explore the mechanism and drug resistance of targeted therapy of malignant melanoma.
8.Pulmonary Hypertension in Adult With Late-onset Glycogen Storage Disease Type Ⅱ(Pompe Disease):a Case Report
Lixing HU ; Qin LUO ; Zhihui ZHAO ; Li DENG ; Tao YANG ; Qing ZHAO ; Zhihong LIU
Chinese Circulation Journal 2025;40(8):813-815
Glycogen storage disease type Ⅱ,also known as Pompe disease,is an autosomal recessive metabolic myopathy with pulmonary hypertension as a rare complication.We reported a case of pulmonary hypertension in adult with late-onset glycogen storage disease type Ⅱ.Her arterial blood gas results indicated type Ⅱ respiratory failure,lung function indicated severe restricted ventilation dysfunction,sleep monitoring indicated severe sleep apnea hypopnea,severe nocturnal hypoxemia,echocardiography-derived systolic pulmonary pressure was 62 mmHg(1 mmHg=0.133 kPa),electromyography indicated myogenic lesion,and whole exon sequencing indicated GAA gene mutation.Supportive therapy and enzyme replacement therapy are applied in this patient.
9.Effectiveness and Safety of Recombinant Human Brain Natriuretic Peptide for the Treatment of Patients With Right Heart Failure Caused by Pulmonary Arterial Hypertension
Lixing HU ; Qing ZHAO ; Zhihui ZHAO ; Qin LUO ; Li DENG ; Ping JIANG ; Zhihong LIU
Chinese Circulation Journal 2025;40(8):782-786
Objectives:To observe the effectiveness and safety of recombinant human brain natriuretic peptide(rhBNP)for the treatment of patients with right heart failure caused by pulmonary arterial hypertension(PAH).Methods:A total of 421 patients with right heart failure caused by PAH who were hospitalized in Fuwai Hospital from January 2019 to June 2024 were retrospectively included in this study.All patients were treated with rhBNP on top of conventional therapy.24 h urine volume,body weight,liver and renal function index,electrolyte,uric acid,red blood cell distribution width(RBCDW),cardiac function,blood pressure and heart rate before and after the treatment of rhBNP were compared.Clinical symptoms,signs and the occurrence of adverse events during treatment were also observed.Results:Compared with baseline,after treatment with rhBNP,the 24 h urine volume increased.The levels of body weight,transaminase,total bilirubin,direct bilirubin,uric acid,RBCDW,systolic blood pressure,heart rate,and N-terminal pro-B-type natriuretic peptide significantly decreased(all P<0.05).There were no statistically significant differences in the levels of serum creatinine,and tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio(both P>0.05).Dyspnea and lower limbs edema were improved in 75.2%cases(227/302)and 66.9%cases(281/420)respectively.The incidence of adverse events and severe adverse events during rhBNP treatment were 1.2%(5/421)and 0.5%(2/421)respectively.Conclusions:Adding rhBNP on top of standard medication can effectively increase 24 h urine volume,reduce body weight,improve some prognostic indicators,improve the clinical symptoms and signs of heart failure without negatively affecting the renal function in right heart failure patients caused by PAH.Blood pressure should be closely monitored during the treatment process.
10.Interventional Treatment Strategy for Different Types of Pulmonary Artery Lesions in Chronic Thromboembolic Pulmonary Hypertension
Xin LI ; Tao YANG ; Yi ZHANG ; Qin LUO ; Qing ZHAO ; Qixian ZENG ; Sicheng ZHANG ; Zhihui ZHAO ; Zhihong LIU
Chinese Circulation Journal 2025;40(2):190-196
Chronic thromboembolic pulmonary hypertension is characterised by the persistent obstruction of the proximal pulmonary arteries by organized thrombi and peripheral microvascular disease,which can lead to right-sided heart failure and mortality.Pulmonary endarterectomy enables complete removal of visible obstructive elements within the pulmonary arteries and is recommended for operable patients.Nevertheless,over 40%of patients are precluded from pulmonary endarterectomy because of factors such as surgically inaccessible lesions,compromised general health status,or concurrent comorbidities or still with residual pulmonary hypertension after pulmonary endarterectomy.For inoperable patients or those with residual pulmonary hypertension after pulmonary endarterectomy,balloon pulmonary angioplasty is an effective therapeutic option,which could significantly improve the hemodynamic,exercise tolerance and outcome of the patients.With the emerging accumulation of clinical experience and evidence,2022 European Society of Cardiology/European Respiratory Society guidelines of pulmonary hypertension recommend balloon pulmonary angioplasty as an alternative therapeutic option for these patients.However,different types of lesions may have their own lesion characteristics,the strategy and device of balloon pulmonary angioplasty should thus be individually considered for different lesions,in fact,the success rate of treatment and the incidence rate of complications are varied significantly.Therefore,the aim of this review is to comprehensively summarize the existing studies on balloon pulmonary angioplasty treatment strategies for different types of lesions and the management of complications to provide guidance and reference for clinicians.

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