1.Tranexamic acid-fatty alcohol polyoxyethylene ether conjugation/PVA foam for venous sclerotherapy via vascular damage and inhibiting plasmin system.
Jizhuang MA ; Keda ZHANG ; Wenhan LI ; Yu DING ; Yongfeng CHEN ; Xiaoyu HUANG ; Tong YU ; Di SONG ; Haoran NIU ; Huichao XIE ; Tianzhi YANG ; Xiaoyun ZHAO ; Xinggang YANG ; Pingtian DING
Acta Pharmaceutica Sinica B 2025;15(6):3291-3304
Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEOx-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEOx) by ester bonds. AEOx-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEOx-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEOx-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEOx-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.
2.Buzhong Yiqitang Induces Ferroptosis by Regulating PCBP1 to Attenuate Cisplatin Resistance in Non-small Cell Lung Cancer
Yuetong LIU ; He LI ; Qirui MU ; Jingyi HUANG ; Haoran CAI ; Chunying LIU ; Yuan GAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):90-97
ObjectiveTo explore the molecular mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer (NSCLC) by inducing ferroptosis via poly(rC)-binding protein 1 (PCBP1). MethodsThe serum containing Buzhong Yiqitang was prepared and cisplatin-resistant human non-small cell lung cancer (NSCLC) cells (A549/DDP) were cultured and randomly grouped as follows: Blank (10% blank serum), model (10% blank serum+20 mg·L-1 cisplatin), Buzhong Yiqitang (10% serum containing Buzhong Yiqitang+20 mg·L-1 cisplatin), Fe-1 (10% blank serum+20 mg·L-1 cisplatin+5 μmol·L-1 Fe-1), and Buzhong Yiqitang+Fe-1 (10% serum containing Buzhong Yiqitang+20 mg·L-1 cisplatin+5 μmol·L-1 Fe-1). Firstly, PCR Array was used to screen ferroptosis-related genes regulated by Buzhong Yiqitang, and PCBP1 was identified as the target for studying the attenuation of cisplatin resistance by Buzhong Yiqitang. Subsequently, the median inhibitory concentration (IC50) of cisplatin in each group was determined by the cell counting kit-8 (CCK-8) method and the resistance index (RI) was calculated. The ultrastructure of A549/DDP cells in each group was observed by transmission electron microscopy. The protein levels of PCBP1 and glutathione peroxidase 4 (GPX4) were determined by Western blot. The lipid reactive oxygen species (ROS) content in each group was determined by the C11-BODIRY 581/591 fluorescence probe. The ferrous ion assay kit was used to measure the ferrous ion content in each group. The malondialdehyde (MDA) assay kit was used to determine the MDA content in each group. ResultsCompared with model group, the IC50 of cisplatin and the RI of A549/DDP cells decreased in the Buzhong Yiqitang group (P<0.05) but increased in the Fe-1 group (P<0.05). The IC50 of cisplatin and the RI of A549/DDP cells in the Buzhong Yiqitang+Fe-1 group were lower than those in the Fe-1 group (P<0.05). Compared with the model group, the Buzhong Yiqitang group showed obvious mitochondrial ferroptosis, while the mitochondrial damage became less obvious after Fe-1 treatment. Compared with that in the Fe-1 group, the mitochondrial ferroptosis was aggravated after the intervention with Buzhong Yiqitang. Compared with blank group, the model group showed down-regulated expression levels of PCBP1 and GPX4 (P<0.05) and increased content of lipid ROS, ferrous ions, and MDA (P<0.05) in A549/DDP cells. Compared with model group, the Buzhong Yiqitang group showed down-regulated expression levels of PCBP1 and GPX4 (P<0.05) and increased content of lipid ROS, ferrous ions, and MDA (P<0.05), while the Fe-1 group showed up-regulated expression levels of PCBP1 and GPX4 (P<0.05) and reduced content of lipid ROS, ferrous ions, and MDA (P<0.05). Compared with the Fe-1 group, the Buzhong Yiqitang+Fe-1 group showed down-regulated expression levels of PCBP1 and GPX4 and increased content of lipid ROS, ferrous ions, and MDA (P<0.05). ConclusionBuzhong Yiqitang attenuated cisplatin resistance in NSCLC by regulating PCBP1 to induce ferroptosis.
3.Camrelizumab-induced intranasal reactive hemangiomas: a case series report
Haoran HUANG ; Lijun XU ; Danfan LIN ; Haocheng TANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(11):1413-1418
Objective:To analyze the clinical characteristics, treatment options, and prognosis of intranasal reactive hemangioma associated with camrelizumab therapy.Methods:Clinical data from patients with intranasal reactive hemangioma associated with camrelizumab treated at Nanfang Hospital of Southern Medical University from February 2021 to April 2022 were collected, including patients′ demographics, clinical symptoms, endoscopic lesion characteristics, enhanced MRI results of the sinuses, pathological examination results, treatment plans, and disease outcomes at the last follow-up.Results:A total of 5 patients with intranasal reactive hemangioma were included, comprising 3 males and 2 females, with ages ranging from 21 to 61 years. The primary diseases of these patients included advanced primary liver cancer and nasopharyngeal carcinoma with liver and lung metastases. All patients presented with recurrent nasal bleeding and progressively worsening nasal obstruction, rated as grade 2 adverse reactions. The onset of intranasal reactive hemangioma was observed after 2 to 15 cycles of camrelizumab injections, with lesions primarily located in the common nasal passage and nasopharynx. Endoscopically, intranasal reactive hemangiomas appeared as dark red, narrow-based, and easily bleeding tumor-like lesions. Enhanced MRI showed mild to moderate heterogeneous enhancement. All patients underwent endoscopic resection of hemangioma via a lesion-targeted technique, with the surgical procedure confined to the removal of the grossly visible tumor mass and 5 mm surrounding mucosal margins around the tumor bed. Postoperative pathological examination revealed hemangioma characteristics, including variably sized vascular lumens and endothelial cell proliferation. Follow-up duration ranged from 6 to 12 months, during which none of the patients experienced recurrence of intranasal reactive hemangioma.Conclusion:Prompt surgical excision of camrelizumab-induced intranasal reactive hemangioma is recommended upon diagnosis to mitigate bleeding complications.
4.A Geant4-based research on radiation field distribution in a 9 MeV e-FLASH treatment room
Deqi CHENG ; Qin YANG ; Xufan HUANG ; Peng WU ; Haoran XIE ; Jing XIA ; Erfeng WANG ; Guofu YU ; Yu JIANG ; Xianhong LIU
Chinese Journal of Radiological Medicine and Protection 2025;45(11):1152-1156
Objective:To investigate the radiation field distribution characteristics in a 9 MeV electron FLASH (e-FLASH) linear accelerator treatment room.Methods:The Geant4 Monte Carlo program was employed for physical simulating of the radiation field distribution inside and outside the treatment room under a single-beam delivery condition with a total dose of 50 Gy at the reference point and a dose rate of 250 Gy/s. High-sensitivity radiation detectors (AT1123) were used to validate the measurements at key points.Results:The dose rate at the reference point was approximately 9×10 11 μSv/h. Due to the scattering and shielding effects, the deviation of the attenuation rate from the inverse-square law was observed and the isodose lines exhibited spatial drift. Measured dose rates at key points showed good agreement with the simulation result, with a maximum deviation within 30%. Conclusions:The complex radiation field distribution can be effectively simulated using Geant4 in an e-FLASH treatment room. This indicated the Geant4 is not only applicable for the shielding calculations in e-FLASH radiotherapy facilities, but also for the design optimization through, reduction of trial-and-error iterations and engineering costs.
5.Analysis of serum 25-hydroxyvitamin D 3 levels and prognosis in patients with amyotrophic lateral sclerosis
Hongfen WANG ; Haoran WANG ; Yanchen LIN ; Jiongming BAI ; Mao LI ; Xusheng HUANG
Chinese Journal of Internal Medicine 2025;64(4):325-332
Objective:To evaluate serum 25-hydroxyvitamin D 3 [25(OH)D 3] as a potential biomarker for amyotrophic lateral sclerosis (ALS) severity and to identify risk factors influencing ALS prognosis. Methods:This study included 217 ALS patients hospitalized at the Department of Neurology, First Medical Center, Chinese PLA General Hospital, between October 2018 and October 2021, who met the revised El Escorial diagnostic criteria. A cross-sectional analysis assessed differences in clinical indicators-including the ALS Functional Rating Scale-Revised (ALSFRS-R) and forced vital capacity percentage (FVC%)-across different serum 25(OH)D 3 levels. The correlation between 25(OH)D 3 levels and individual ALSFRS-R components was also examined. Conduct a prospective cohort study to identify independent risk factors affecting the survival time of ALS patients. Results:Among three groups categorized by serum 25(OH)D 3 levels, there were significant differences in the proportion of males ( χ2=10.51, P<0.05). Serum 25(OH)D 3 levels correlated positively with lower limb function scores in the ALSFRS-R ( r=0.05, P<0.05), but they were not identified as an independent risk factor for survival ( HR=0.98, 95% CI 0.93-1.04, P>0.05). In contrast, delayed diagnosis( HR=0.94, 95% CI 0.89-0.99, P<0.05) and reduced FVC%( HR=0.94, 95% CI 0.97-0.99, P<0.05) were independent predictors of shorter survival. Conclusion:Serum 25(OH)D 3 levels differ by gender distribution and may be linked to better lower limb function in ALS patients. However, their role in prolonging survival remains uncertain.
6.Effects of childhood trauma on resting blood pressure, heart rate, and heart rate variability in patients with depression
Kuaikuai LIU ; Fanfan HUANG ; Lulu YU ; Meina BAI ; Wenting LU ; Bufan LIU ; Tianyu ZHAO ; Ruojia REN ; Yuanyuan GAO ; Haoran ZHANG ; Xueyi WANG
Chinese Journal of Psychiatry 2025;58(9):681-689
Objective:To explore the effects of childhood trauma on resting blood pressure, heart rate, and heart rate variability in patients with depression.Methods:A cross-sectional study was designed to prospectively collect clinical data on a total of 163 patients with depression, including 47 males and 116 females, aged 18-50 years,with mean[ M( Q1, Q3)] [29.0, (21.0, 37.0)]years, who were either the outpatients or the inpatients in the Mental Health Center of the First Hospital of Hebei Medical University from September 2022 to June 2024. The Childhood Trauma Questionnaire-Short form (CTQ-SF) was used to assess the experience of abuse and neglect during childhood. According to the CTQ-SF score, the subjects were divided into a trauma group ( n=80) and a non-trauma group ( n=83). The 17-item Hamilton Depression Scale (HAMD 17) and Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms in the participants, respectively. A digital blood pressure monitor and an autonomic nervous system response detector were employed to measure resting blood pressure, heart rate, and heart rate variability (HRV). Spearman correlation analysis was used to examine the relationships between childhood trauma and resting blood pressure, heart rate, and HRV. Multiple linear regression analysis was performed to analyze factors influencing these parameters. The Bootstrap method was employed to test the potential mediating role of parasympathetic nervous system activity in the relationships between childhood trauma and resting blood pressure, and heart rate. Results:No significant difference was observed in resting heart rate between the trauma and non-trauma groups ( P>0.05). However, the trauma group exhibited higher resting systolic and diastolic blood pressure [(123.3±9.1) mmHg (1 mmHg=0.133 kPa) vs(116.9±10.8) mmHg, (80.0±8.6) mmHg vs (77.0±8.0) mmHg; Z=4.08, 2.24, all P<0.05]. HRV indices, including the standard deviation of normal to normal interval (SDNN), root mean square of successive differences (RMSSD), total power (TP), low frequency (LF), and high frequency (HF), were significantly lower in the trauma group [25.3 (19.4, 30.4) me vs 36.3 (27.4, 49.0) ms, 18.3 (12.9, 27.2) me vs 26.2 (19.0, 38.5) ms, 6.0(5.4, 6.5)ms 2vs 7.0(6.3, 7.4)ms 2,4.4(3.7,5.3)ms 2vs 5.8(4.9,6.3)ms 2, 4.2(3.4, 5.2)ms 2vs 5.2(4.6, 6.1)ms 2, respectively; all P<0.001]. Spearman correlation analysis showed that childhood trauma experiences in patients with depression were positively correlated with resting systolic blood pressure and diastolic blood pressure ( r=0.309, 0.236; P<0.01), childhood trauma was negatively correlated with HRV (SDNN, RMSSD, TP, LF, HF) ( r=-0.264, -0.274, -0.271, -0.235, -0.279; all P<0.01). Multiple linear regression analysis showed that childhood trauma was positively correlated with resting-state systolic blood pressure and resting-state diastolic blood pressure ( β=0.305, 0.291; all P<0.001). Childhood trauma was negatively correlated with RMSSD, TP, LF, and HF( β=-0.244, -0.249, -0.233, -0.263; all P<0.01). Mediation effect analysis showed that parasympathetic activity partially mediated the relationship between childhood trauma and resting systolic blood pressure (effect size 0.04, standard error 0.02, 95% CI=0.01-0.09), accounting for 14.29% (0.04/0.28) of the total effect. Conclusion:Childhood trauma experiences are associated with elevated resting blood pressure and reduced HRV in patients with depression. Decreased parasympathetic activity partially mediates the relationship between childhood trauma and elevated resting systolic blood pressure in these patients.
7.Diagnosis of MRI in Spontaneous Spinal Subdural Hematoma
Haiyan GAO ; Huishan GAO ; Haoran HUANG ; Liang LI ; Jun CHEN
Chinese Journal of Medical Imaging 2025;33(7):775-779
Purpose To summarize the MRI characteristics of patients with spontaneous spinal subdural hematoma,so as to strengthen the awareness to this disease,and to improve the clinical diagnosis and treatment ability.Materials and Methods A retrospective analysis was performed on five patients with spontaneous spinal subdural hematoma diagnosed and treated in Qingdao Chengyang District People's Hospital from January 2021 to December 2023.Plain MRI and enhanced MRI were performed 6-24 hours after onset,and the imaging characteristics were analyzed.Combined with the dynamic American Spinal Injury Association(ASIA)grading score and disease progression,three patients were treated with surgery and two patients with conservative treatment.Results All patients were followed up for 6-15 months.Among the five patients,the hematoma was distributed at the cervicothoracic junction in two cases,the upper thoracic segment in one case and the thoracolumbar segment in two cases;covering 3-6 segments in two cases,2-3 segments in two cases and 1 segment in one case;hematoma was located at the ventral side of the dural sac in two cases,and the dorsal side of the dural sac in three cases.Postoperative pathology showed that one case was simple blood clot,and two cases were blood clot with a large number of neutrophil infiltration.One case was hyperacute phase with isointensity on T1WI and high signal on T2WI,three cases were acute phase with isointensity on T1WI and low signal on T2WI,and one case was subacute phase with high signal on T1WI and low signal on T2WI.Enhanced scanning showed that one case was uneven enhancement,one case was irregular edge enhancement and three cases had no obvious enhancement.ASIA grade of two cases returned to E,one case returned to C after surgery,and lower limb muscle strength of two cases returned to E after conservative treatment,and MRI reexamination showed that the hematoma was absorbed.Conclusion MRI has strong sensitivity for the lesions of patients with spontaneous spinal subdural hematoma,which can accurately show the location and size of the hematoma,help to distinguish the progression of the disease,and has great significance for clinical diagnosis and treatment.
8.Clinical characteristics and molecular function of ubiquitin-like containing PHD and RING finger domains 1 in soft tissue sarcoma
Yijin YAN ; Huan WANG ; Yifan DING ; Haoran XU ; Weihua HU ; Huang FANG
Journal of Clinical Surgery 2025;33(7):735-740
Objective To explore the expression pattern and molecular function of ubiquitin-like containing PHD and RING finger domains 1(UHRF1)gene in soft tissue sarcoma(STS),as well as its correlation with clinical characteristics and prognosis of STS.Methods RNA data and related clinical data of 263 STS tissues were obtained from Cancer Genome Atlas(TCGA).Wilcoxon rank-sum test was used to analyze correlation between two groups of data;Spearman correlation coefficient analyzed the top 35 co-expressed genes positively and negatively correlated with UHRF1 expression in STS database,ggplot2 statistical package displayed co-expressed gene heatmap,Pearson correlation coefficient showed correlation between UHRF1 expression and expression of the top 10 genes in the heatmap;different UHRF1 gene expression groups in STS were analyzed using DESeq2 package,ggplot2 package was used to draw volcano plots,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyzed differentially expressed genes(DEGs)and protein functions,ggplot2 package for visualization,and cluster Profiler package for statistical analysis;STRING web was used to establish PPI network of DEGs,and the MCC algorithm in CytoHubba of Cytoscape was used to analyze hub genes.Results In STS,UHRF1 gene was significantly correlated with its histological type(liposarcoma 22.2%,synovial sarcoma 3.8%,leiomyosarcoma 40.7%,malignant peripheral nerve sheath tumor 3.8%,myxofibrosarcoma 9.6%,pleomorphic sarcoma 19.9%,P=0.001),tumor necrosis(none 38.8%,focal necrosis 20.8%,moderate necrosis 33.8%,extensive necrosis 6.6%,P=0.010),and tumor metastasis(no metastasis 67%,metastasis 33%,P<0.001).In different clinical subgroups(age,gender,histological type,residual tumor,tumor necrosis,tumor depth,margin status,tumor multifocality,radiotherapy),high expression of UHRF1 led to poor prognosis of overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI);Three prognostic factors above were simultaneously shortened in the following five subgroups:namely residual tumor R0 and R1,tumor necrosis extensive,focal and moderate,tumor depth deep,positive margin status,tumor without multifocality.Analysis of the top 10 co-expressed genes associated with UHRF1 expression revealed that the associated positive genes were PAGE5,LINC01425,LCEP3,SERPINB7,AC074031.1,LCE3A,LCE2A,PAGE2B,MYF5,and AC037486.1(P<0.05);the associated negative genes were CDH19,CSN1S1,TAC3,AC103563.7,SAA1,CHST8,PRLHR,MIR202HG,IGHV1-24,and ART4(P<0.05).A total of 3 029 DEGs of UHRF1 in STS were obtained with a threshold of|log2 fold-change(FC)|>1.0 and adjusted P value<0.05,in which 1 228 genes were up-regulated and 1 801 genes were down-regulated;GO enrichment analyed primary biological processes(BP),original cellular components(CC),and original molecular functions(MF),and KEGG enrichment analyed signaling pathways.A total of 343 DEGs including 133 up-regulated genes and 210 down-regulated genes,were obtained with a threshold of|log2 fold-change(FC)|>2.0 and adjusted P value<0.05.The top 10 hub genes were analyzed.The top 3 hub genes were GCG,SST and SHH,respectively.Conclusion UHRF1 is significantly correlated with histological type,tumor necrosis,metastasis,OS,DSS,and PFI events in STS.In co expressed genes model and molecular functions of related positive and negative genes involved in multiple biological processes;The network of differentially expressed genes and protein product interactions involved in mechanisms of occurrence and development of the disease,and provided new ideas for in-depth researches on STS.
9.Progress in pathogenesis and treatment of diabetic neuropathy regulated by microglia polarization
Li ZHANG ; Hongmin YANG ; Jiao HU ; Sirui YAO ; Haoran XU ; Wendi LUO ; Tao XU ; Bo HUANG
Chinese Journal of Pathophysiology 2025;41(4):766-774
Diabetic neuropathy(DN)is a prevalent chronic complication of diabetes,characterized by a com-plex pathogenesis involving various cell types and molecular pathways.Research indicates that microglia,serving as the innate immune cells of the central nervous system,are pivotal in the development of DN.In recent years,with the in-depth understanding of the pathogenesis of DN,targeting microglia polarization has become a new research hotspot.This article provides an overview of current research on the regulatory mechanisms of microglia polarization,the impact of mi-croglia polarization on DN,and treatment strategies that target microglia polarization to improve DN.The objective is to elucidate the pivotal role of microglia in the pathogenesis of DN,and assess the efficacy and constraints of existing and emerging treatment methods targeting microglia,in order to offer a fresh perspective for future research and clinical treat-ment of DN.
10.A Geant4-based research on radiation field distribution in a 9 MeV e-FLASH treatment room
Deqi CHENG ; Qin YANG ; Xufan HUANG ; Peng WU ; Haoran XIE ; Jing XIA ; Erfeng WANG ; Guofu YU ; Yu JIANG ; Xianhong LIU
Chinese Journal of Radiological Medicine and Protection 2025;45(11):1152-1156
Objective:To investigate the radiation field distribution characteristics in a 9 MeV electron FLASH (e-FLASH) linear accelerator treatment room.Methods:The Geant4 Monte Carlo program was employed for physical simulating of the radiation field distribution inside and outside the treatment room under a single-beam delivery condition with a total dose of 50 Gy at the reference point and a dose rate of 250 Gy/s. High-sensitivity radiation detectors (AT1123) were used to validate the measurements at key points.Results:The dose rate at the reference point was approximately 9×10 11 μSv/h. Due to the scattering and shielding effects, the deviation of the attenuation rate from the inverse-square law was observed and the isodose lines exhibited spatial drift. Measured dose rates at key points showed good agreement with the simulation result, with a maximum deviation within 30%. Conclusions:The complex radiation field distribution can be effectively simulated using Geant4 in an e-FLASH treatment room. This indicated the Geant4 is not only applicable for the shielding calculations in e-FLASH radiotherapy facilities, but also for the design optimization through, reduction of trial-and-error iterations and engineering costs.

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