1.Mechanosensitive ion channel-related genes in hepatocellular carcinoma:Unraveling prognostic genes and their roles in drug resistance and immune modulation
Xinyan HUO ; Shiyu JIANG ; Sihuang WU ; Qinghai LIAN ; Hui CHEN
Liver Research 2025;9(1):36-48
Background and aims:Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,and its etiology involves a complex interplay of genetic and environmental factors.Despite ad-vancements in our understanding of HCC biology and the development of novel therapeutic strategies,the molecular mechanisms underlying its onset,progression,and resistance to therapy remain largely vague.This study aimed to investigate the role of mechanosensitive ion channel-related genes(MICRGs)in HCC,focusing on their potential as prognostic biomarkers and their involvement in immune modulation and drug resistance.Methods:A comprehensive analysis was conducted using The Cancer Genome Atlas database to identify MICRGs that are upregulated in HCC.Gene expression profiling,bioinformatics tools,and functional experiments were employed to elucidate the role of these channels.In addition,protein-protein interaction(PPI)network analyses and enrichment analyses were performed to explore the biological significance of these genes.An immune cell infiltration analysis was also conducted to understand MICRG-related immune landscape.Single-cell RNA sequencing(scRNA-seq)data were utilized to identify MICRGs in different cell types within the HCC tissue.Deep-learning neural network analysis across patient cohorts was conducted to identify genes associated with sorafenib resistance.Knockdown ex-periments,cell viability assays,and apoptosis assays on HCC cell lines were performed to examine the role of Piezo-type mechanosensitive ion channel component 1(PIEZO1)in sorafenib resistance.Results:The analysis identified a subset of MICRGs,including PIEZO1,that were significantly upregulated in HCC and associated with poor prognosis.The PPI network analysis revealed complex interactions among these genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses proposed the involvement of these genes in calcium signaling pathways.Immune cell infiltration analysis demonstrated distinct associations between MICRGs and various immune subpopulations,highlighting their potential roles in immune modulation.scRNA-seq data indicated the upregulation of MICRGs in various cell types in HCC tissues,particularly in endothelial cells and tumor-associated macrophages.Deep-learning neural network analysis across different patient cohorts identified PIEZO1 as a crucial regulator of sorafenib resistance in HCC,which was further validated by functional assays on HCC cell lines.Conclusions:This study provides evidence that MICRGs,particularly PIEZO1,take on crucial roles in HCC progression and drug resistance.The upregulation of PIEZO1 in HCC cells is associated with poor prog-nosis and resistance to sorafenib.These findings indicate that PIEZO1 could serve as a potential thera-peutic target for overcoming drug resistance and a prognostic biomarker in HCC.Future studies should focus on validating these findings in larger patient cohorts and exploring the functional implications of targeting PIEZO1 in preclinical models.
2.Evaluation of clinical effect of position pillows for neuraxial anesthesia
Jing ZHANG ; Jiechu WANG ; Xinyan ZHU ; Xiaoqing ZHANG ; Dong WANG ; Xueyao YU ; Jinjin HUO ; Zhukai CONG ; Yi LIU ; Wei LIU ; Liyuan HAO ; Li FAN ; Xiaoxiao LI
Chinese Journal of Anesthesiology 2024;44(9):1135-1138
Objective:To evaluate the clinical effect of the position pillows for neuraxial anesthesia.Methods:This was a prospective randomized controlled trial. Four hundred and twelve patients regardless of gender, aged ≥18 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, who underwent elective surgery under neuraxial anesthesia at Peking University Third Hospital from February to October 2023, were selected and divided into 2 groups ( n=206 each) using a random number table method: pillow group (P group) and control group (C group). Group C underwent the conventional procedure for neuraxial anesthesia. The patients were placed in a position using the position pillow on the basis of oral education before routine anesthesia in group P. The success rate of puncture at first attempt, puncture time and position placement time were recorded. The adjustment of position, body movement and occurrence of discomfort during the puncture were also recorded. The visual analogue scale score was used to evaluate the level of anxiety before positioning, after positioning and after anesthesia. The visual analogue scale score was used to evaluate the patient′s comfort and the operator′s satisfaction with position after the anesthesia was completed. Results:Compared with group C, the time for positioning was significantly shortened, the anxiety level was decreased after positioning and after anesthesia, the rate of improvement in anxiety was increased, the scores for the patient′s comfort and the operator′s satisfaction with position were increased ( P<0.05), and no significant changes were found in the success rate of puncture at first attempt, puncture time and incidence of body movement during the puncture and incidence of the adjustment of position ( P>0.05). No discomfort was observed in either group during the puncture. Conclusions:This new type of position pillows for the neuraxial anesthesia can not only optimize the effect of position placement, but also improve the patients′ comfort.
3.Studies on the therapy of endometriosis by antiangiogenesis with endostatin gene
Xinyan ZHANG ; Xiaoxi HUO ; Haifang LIU
Medical Journal of Chinese People's Liberation Army 2001;0(07):-
Objective To study the inhibitory effect of recombinant adenoviruses carrying the mouse endostatin gene on the therapy of endometriosis in nude mice.Methods Animal endometriosis models were established by inoculating human endometrial fragments.Mice were randomly divided into three groups(10 each):PBS control group,Ad-lacZ group and Ad-mEndo therapy group when ectopic lesion diameter reached 5-10mm.The ectopic lesion size was measured every day.The expression of endostatin in ectopic lesion was detected by immunohistochemical stainining.The microvessel density(MVD) of ectopic lesion was traced by CD34 immunohistological labeling.Meanwhile,the contents of steroid hormone and histological changes in mice uterus and ovary were detected.Results The titer of the recombinant adenovirus was about 5.0?109pfu/ml.The endostatin gene was transferred into mice successfully and expressed effectively.The lesion volume was significantly less in Ad-mEndo group(34.3?11.2mm3) than that in Ad-lacZ group(93.3?10.7mm3) and PBS group(90.4?18.7mm3,P

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