1.Research progress of inducing ferroptosis of cancer stem cells against colorectal cancer
Li-Na GONG ; Meng-Ling YUAN ; Xue-Ying CHENG ; Chen-Yang XU ; Jun PAN ; Qiu-Tong CHEN ; Ling WANG ; Zi-Li ZHANG ; Mei GUO
Chinese Pharmacological Bulletin 2024;40(6):1030-1034
Cancer stem cell(CSC)are the"seed"cells in the occurrence,development,metastasis and recurrence of colorectal cancer.Targeted killing of CSC provides a new target for anti-colorectal cancer therapy.Ferroptosis is an iron-dependent cell death mode due to the abnormal accumulation of intracellular i-ron ions,which results in the massive reactive oxygen species(ROS)and lipid peroxides,leading to cell death.Studies have shown that cancer stem cells are more enriched in iron ions than non-CSC,which provides a new perspective for targeting ferropto-sis in cancer stem cells against colorectal cancer.This article re-views the research progress of inducing CSC ferroptosis in the treatment of colorectal cancer,such as targeted regulation of SLC7A11 expression in CSC,chelating iron in CSC lysosomes,targeting CSC phenotypic plasticity,reversing CSC iron homeo-stasis,and targeting CSC lipid droplet metabolism induce CSC ferroptosis,which provides new ideas for anti-tumor therapy.
2.Mechanisms of puerarin on anti-glioma effects by targeting on mitochondria
Ge-Ge SHENG ; Zi-Han FENG ; Yu-De CHENG ; Hai-Li ZHU ; Shao-Hui CHEN
Chinese Pharmacological Bulletin 2024;40(7):1317-1324
Aim To investigate the effects of puerarin on the proliferation,migration,and apoptosis of glio-blastoma cells and the underlying mechanisms.Meth-ods Differentially expressed genes associated with gli-oma and mitochondrial disease were analyzed using the GEO database.Cytotoxicity was detected by CCK-8 as-say.Cell migration was detected by the scratch wound healing assay and Transwell assay.Cell proliferation was assessed by EdU assay.Apoptosis level was meas-ured by TUNEL assay.Mitochondrial membrane poten-tial was detected by Mito-Tracker assay.ATP contents were detected using the ATP kit.The protein expres-sion levels were detected by Western blot.Antitumor efficacy of puerarin was analyzed using subcutaneous xenograft.Results There were 178 genes co-related differentially expressed genes in glioma and mitochon-drial disease.Core genes of co-related differentially ex-pressed genes were screened by GO and KEGG enrich-ment analyses,and the interaction networks.Among them,ubiquitin C(UBC)level was highly expressed in tissues of glioma patients.Puerarin could bind to UBC and reduce UBC expression at the animal and cell levels.Puerarin treatment inhibited the growth of glio-ma and decreased cell proliferation,migration and pro-moted cell apoptosis signals.Meantime,puerarin treat-ment also reduced mitochondrial membrane potentials and ATP contents,and down-regulated the levels of UBC related proteins.Conclusion Puerarin inhibits the proliferation,migration and promotes apoptosis of glioma cells.The mechanism of induction of mitochon-drial dysfunction is involved.
3.Role and mechanism of neuronal restriction silencing factor REST/NRSF in regulation of epilepsy
Hui LIU ; Bai-Hui YU ; Ya-Qi WANG ; Yi-Ling CHEN ; Zi-Hao CHENG ; Jia-Rui MA ; Zi-Shuo KANG ; Fan ZHANG
Chinese Pharmacological Bulletin 2024;40(9):1727-1734
Aim To investigate the effect and role of neuronal restriction silencing factor(REST/NRSF)in epilepsy disorder.Methods Immunohistochemistry,immunofluorescence,Western blot and qPCR tech-niques were used to detect REST/NRSF expression levels in hippocampal tissues of mice induced by kainic acid and human brain tissue.Viral injections,EEG re-cordings and behavioral methods were used to test the effects on epileptic mice after knockdown and overex-pression of REST/NRSF in the hippocampal CA1 re-gion,respectively.Results The positive rate of REST/NRSF in the lesions of epileptic patients was significantly higher compared with that in the control group.The levels of REST/NRSF protein and mRNA in the CA1 region of the hippocampus of mice in the KA model group were significantly higher.Kv7.2 and Kv7.3 potassium channel mRNA expression levels were significantly down-regulated.Significant up-regu-lation of REST/NRSF expression levels was observed in mouse hippocampus after NMDA injection.Knock-down of REST/NRSF in the CA1 region of hippocam-pus significantly elevated the expression levels of Kv7.2 and Kv7.3 potassium channel mRNAs.The fre-quency of EEG spiking and sharp-wave issuance and epileptic seizure grade were significantly lower.Over-expression of REST/NRSF in the CA1 region of hippo-campus significantly reduced the mRNA expression lev-els of Kv7.2 and Kv7.3 potassium channels.The fre-quency of EEG spiking and sharp-wave issuance was significantly higher and epileptic symptoms were exac-erbated.Conclusion REST/NRSF in mouse hipp-ocampal brain regions is involved in epileptic disease development through transcriptional regulation of Kv7.2 and Kv7.3 potassium channels.
4.Changes and clinical significance of NLRP3 inflammasomes and related factors in patients with spinal fracture com-plicated with acute spinal cord injury
Yuan-Yuan DU ; Hao YANG ; Cheng-Cheng CHEN ; Zi-Yan HE
China Journal of Orthopaedics and Traumatology 2024;37(7):684-688
Objective To investigate the changes and clinical significance of NOD like receptor protein 3(NLRP3)in-flammasomes and related factors in patients with spinal fractures complicated with acute spinal cord injury(SCI).Methods Eighty-six spinal fracture patients complicated with acute SCI admitted to hospital from June 2019 to March 2022 were selected as SCI group,There were 48 males and 38 females,with an average age of(43.48±6.58)years old.And 100 healthy volunteers who underwent physical examination during the same time were selected as control group,including 56 males patients and 44 females patients,with an average age of(45.13±6.43)years old.Peripheral blood mononuclear cell(PBMC)were collected,and the mRNA expressions of NLRP3 and Caspase-1 were detected.Serum was collected and the levels of interleukin(IL)-1β,IL-18 were detected.According to Frankel's grade,the SCI group was divided into complete injury patients and incomplete injury patients,and according to the Japanese Orthopedic Society(JOA)grade,the SCI group was divided into good prognosis group and poor prognosis group.The difference of NLRP3,Caspase-1,IL-1β,IL-18 among groups were compared,the influ-encing factors for poor prognosis in SCI patients was analyzed by Logistic regression.Results The mRNA expression levels of NLRP3(1.41±0.33)and Caspase-1(1.44±0.35)in PBMC and the levels of IL-1β(45.34±13.22)pg·ml-1,IL-18(40.95±8.77)pg·ml-1 in serum of SCI group were higher than those of the control group[(1.00±0.19),(1.00±0.16),(16.58±4.24)pg·ml-1,(12.57±3.68)pg·ml-1](P<0.05).The mRNA expression levels of NLRP3(1.63±0.34)and Caspase-1(1.67±0.27)in PBMC and the levels of IL-1β(51.09±11.10)pg·ml-1,IL-18(47.65±7.93)pg·ml-1 in serum of patients with complete injury in the SCI group were higher than those of patients with incomplete injury[(1.31±0.27),(1.34±0.33),(42.85±13.36)pg·ml-1,(38.05±7.48)pg·ml-1](P<0.05).The mRNA expression levels of NLRP3(1.66±0.31)and Caspase-1(1.72±0.31)in PBMC and the levels of IL-1β(51.21±11.31)pg·ml-1,IL-18(45.70±7.25)pg·ml-1 in serum,the proportion of complete injury(21 patients),and the proportion of spinal cord edema or bleeding of patients(15 patients)with poor prognosis in the SCI group were higher than those of patients with good prognosis[(1.28±0.26),(1.37±0.36),(42.79±13.25)pg·ml-1、(38.90±8.63)pg·ml-1,5、20 cases](P<0.05).Complete injury and the mRNA expression of NLRP3 in PBMC were the influencing fac-tors for poor prognosis in the SCI group(P<0.05).Conclusion The activation of NLRP3 inflammasomes in patients with spinal fractures complicated with acute SCI is associated with worsening injury and poor prognosis,and NLRP3 expression can serve as a marker for evaluating prognosis.
5.Fever Characteristics and Biomarker Changes of CRS in Patients with Relapsed/Refractory Multiple Myeloma after CAR-T Cell Therapy
Tian HUA ; Jiao-Jiao WANG ; Sheng-Wei JI ; Jia-Ying LIU ; Zi-Han CHEN ; Ling-Yan SHAO ; Hai CHENG ; Jiang CAO
Journal of Experimental Hematology 2024;32(6):1744-1751
Objective:To investigate the correlation of the clinical characteristics,fever characteristics,serum biomarkers with cytokine release syndrome (CRS) in patients with relapsed/refractory multiple myeloma (R/R MM) treated with chimeric antigen receptor T cell (CAR-T) immunotherapy. Methods:104 R/R MM patients who received CAR-T cell therapy at the Affiliated Hospital of Xuzhou Medical University from June 2017 to November 2021 were included,and the correlations of their clinical characteristics,fever characteristics,serum biomarkers with the severity of CRS were analyzed. Results:Among 104 R/R MM patients receiving CAR-T treatment,no CRS was observed in 8 cases (7.7%),and 96 cases (92.3%) developed CRS. Patients with high-risk cytogenetics had a higher risk of developing CRS (P=0.040),while patients who had previously received autologous hematopoietic stem cell transplantation (ASCT) had a lower risk of developing CRS (P=0.004). There was a significant difference in the duration of fever between patients with grade 1-2 and grade 3-5 CRS (P=0.006). The highest body temperature varied among patients with different treatment regimens (P=0.001). The decrease in total protein in patients with CRS was more significant than in patients without CRS (P=0.002). Within one month after CAR-T cell infusion,the degree of albumin recovery in patients with grade 3-5 CRS was lower than that in patients with grade 0-2 CRS (P=0.037). Compared to patients with grade 1-2 CRS,patients with grade 3-5 CRS showed a significant increase in heart rate after CAR-T cell infusion (P=0.013),while IL-6,C-reactive protein (CRP),and serum ferritin (SF) also showed significant increases (P=0.007,P<0.001,P=0.003). Conclusion:High-risk cytogenetics is a risk factor for severe CRS. Long duration of fever is a clinical characteristic of severe CRS. CRP can better reflect the severity of CRS.
6.Improved YOLOv8 model-based object detection method for inspection robot
Bei-Chen YIN ; Zi-Jian WANG ; Zhi CHENG ; Xin-Xi XU
Chinese Medical Equipment Journal 2024;45(3):1-8
Objective To propose a object detection method based on an improved YOLOv8 model to solve the problems of the inspection robot in low accuracy for recognizing pointer-type or obscured meters.Methods Firstly,a YOLOv8 model was chosen as the foundation object detection model,based on which the coordinate attention(CA)mechanism was introduced to enhance the model's understanding of the spatial structure of the input data over long distances;secondly,the original complete IoU(CIoU)loss function was replaced by an efficient IoU(EIoU)loss function to accelerate the convergence of the model's detection frame;finally,the soft non-maximum suppression(Soft-NMS)function took the place of the traditional NMS method to suppress the redundant bounding box smoothly and further improve the detection accuracy.The improved YOLOv8 model(YOLOv8nxt model)was compared with the YOLOv8n model to verify its efficacy for object detection.Results The YOLOv8nxt model with a size of 6.2 M had the position loss decreased by 1.3%,mAP_0.5∶0.95 increased by 1.7%,detection accuracy raised by 0.87%and detection time prolonged by only 0.2 ms when comparted with the YOLOv8n model.Conclusion The improved YOLOv8 model-based object detection method enhances the accuracy and speed of the inspection robot's recognition of meters during movement,and can effectively solve the problems of the inspection robot in the object detection stage.[Chinese Medical Equipment Journal,2024,45(3):1-8]
7.Design,numerical simulation and experimental study of novel oxygenator
Ming-Hao YUE ; Shi-Yao ZHANG ; Ji-Nian LI ; Hui-Chao LIU ; Zi-Hua SU ; Ya-Wei WANG ; Zeng-Sheng CHEN ; Shi-Hang LIN ; Jin-Yu LI ; Ya-Ke CHENG ; Yong-Fei HU ; Cun-Ding JIA ; Ming-Zhou XU
Chinese Medical Equipment Journal 2024;45(3):23-28
Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]
8.Review of application of machine learning in imaging diagnosis and prognosis prediction of cervical spine diseases
Cheng-Kun HONG ; Li-Yuan FU ; Zi-Qian CHEN
Chinese Medical Equipment Journal 2024;45(10):98-106
The current situation of machine learning was reviewed when applied in cervical spine image recognition and processing,cervical spine disease diagnosis and prognosis prediction.The problems and challenges encountered by machine learning were analyzed during its application in cervical spine disease imaging diagnosis and prognosis prediction.It's pointed out the machine learning for cervical spine disease imaging diagnosis and prognosis prediction involved in multicenter large-scale research,standardized data acquisition,enhanced model explaination and improved algorithm explaination and trans-parency.[Chinese Medical Equipment Journal,2024,45(10):98-106]
9.Extracellular vesicles in anti-tumor drug resistance:Mechanisms and therapeutic prospects
Cheng HAO-YANG ; Su GUANG-LIANG ; Wu YU-XUAN ; Chen GANG ; Yu ZI-LI
Journal of Pharmaceutical Analysis 2024;14(7):940-954
Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy.Prior research has illuminated reasons behind drug resistance,including increased drug efflux,alterations in drug targets,and abnormal activation of oncogenic pathways.However,there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment(TME).Recent studies on extracellular vesicles(EVs)have provided valuable insights.EVs are membrane-bound particles secreted by all cells,mediating cell-to-cell communication.They contain functional cargoes like DNA,RNA,lipids,proteins,and metabolites from mother cells,delivered to other cells.Notably,EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs.This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance,covering therapeutic approaches like chemo-therapy,targeted therapy,immunotherapy and even radiotherapy.Detecting EV-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance.Additionally,targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance.We highlight the importance of conducting in-depth mechanistic research on EVs,their cargoes,and functional ap-proaches specifically focusing on EV subpopulations.These efforts will significantly advance the devel-opment of strategies to overcome drug resistance in anti-tumor therapy.
10.Study on the effect of different administration regimens of iprrazole enteric-coated tablets on inhibiting gastric acid secretion
Ting-Yuan PANG ; Zhi WANG ; Zi-Shu HU ; Zi-Han SHEN ; Yue-Qi WANG ; Ya-Qian CHEN ; Xue-Bing QIAN ; Jin-Ying LIANG ; Liang-Ying YI ; Jun-Long LI ; Zhi-Hui HAN ; Guo-Ping ZHONG ; Guo-Hua CHENG ; Hai-Tang HU
The Chinese Journal of Clinical Pharmacology 2024;40(1):92-96
Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH>3 after 20 mg qd and 10 mg bid were 82.64%and 61.92%,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

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