1.The psychological experience of ICU nurses caring for young patients with suicide attempts:a qualitative study
Ruijuan WU ; Li WANG ; Xuehua HE ; Yunxia SHEN ; Jingbang LIU ; Liqing CHEN ; Yiyu ZHUANG
Chinese Journal of Practical Nursing 2025;41(12):913-918
Objective:To explore the psychological experience of ICU nurses caring for young patients with suicide attempts in a general hospital, and to lay a foundation for the study of psychological adjustment and intervention for ICU nurses.Methods:Twelve ICU nurses who had experience of caring for suicide attempted- young patients from Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University were selected by using descriptive qualitative research method and the maximum difference method of the purposive sampling during October to December in 2023, and semi-structured in-depth personal interviews were conducted. Traditional content analysis method was used to sort out and analyze the data and extract the themes.Results:A total of 12 nurses completed the interview, 5 males, 7 females, aged 23-38(29.33 ± 4.14) years, three themes and seven sub-themes were extracted: psychological characteristics of care (avoidance of active communication, fear of care, empathy); the support required for nursing care (support from colleagues; support from nursing managers); self-growth after caregiving (self-growth in terms of life and death, and self-growth in terms of children′s education).Conclusions:ICU nurses have a certain degree of psychological pressure when taking care of young patients with suicide attempts, which will produce empathy for patients and affect their self-values. At the same time, they need support from colleagues and nursing managers. Therefore, general hospitals should pay attention to the psychological state of ICU nurses, carry out the targeted communication training and mental health support for ICU nurses, and help them gain positive nursing career growth and values.
2.Astaxanthin reduces oxaliplatin-induced neuropathic pain through antioxidant mechanisms
Chong CHEN ; Junjie TIAN ; Zan ZHOU ; Ruijuan GAO ; Xuechun TANG ; Yixuan GAO ; Ketao MA ; Li LI ; Junqiang SI
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(4):606-615
Objective To investigate the mechanisms by which astaxanthin(AST)alleviates oxaliplatin(OXA)-induced neuropathic pain through antioxidant pathways so as to provide theoretical basis for clinical intervention.Methods Animal experiments:SD rats were divided into five groups(n=6):control group,OXA(4 mg/kg)group,OXA+Oil group,OXA+AST(5 mg/kg)group,and OXA+AST(10 mg/kg)group.Mechanical and cold pain thresholds were measured at day 0,7,14,and 21.Malondialdehyde(MDA)content and superoxide dismutase(SOD)activity in the dorsal root ganglia(DRG)were detected using the thiobarbituric acid(TBA)method and WST-1 assay,respectively.Western blotting was performed to analyze the expressions of Nrf2 and HO-1.Cell experiments:neuro-2a cells were divided into control group,OXA(50 μmol/L)group,AST(10 μmol/L)group,and OXA(50 μmol/L)+AST(10 μmol/L)group.Cells were treated with nerve growth factor(NGF,50 ng/mL)to induce growth,and morphological changes were observed under an inverted microscope.Intracellular reactive oxygen species(ROS)level and mitochondrial superoxide were measured using DCFH-DA fluorescent probe and MitoSOXTM red,respectively.Mitochondrial function was assessed by JC-1 assay.Western blotting was used to detect Nrf2 and HO-1 expressions.Results Animal experiments:① Mechanical and cold pain thresholds were reduced in OXA and OXA+Oil groups(P<0.05),while AST significantly increased these thresholds in OXA-treated rats(P<0.05).② SOD activity decreased while MDA content increased in the DRG of OXA-treated rats(P<0.05).AST restored SOD activity and reduced MDA level(P<0.05,P<0.01).③ Western blotting showed elevated Nrf2 and HO-1 expressions in OXA group(P>0.05),which were further upregulated by AST(P<0.05,P<0.01).Cell experiments:① OXA reduced the number of neurite-bearing cells and shortened the average neurite length(P<0.05).Inverted microscopic observation revealed that AST intervention increased both parameters(P<0.01,P<0.001).② OXA increased intracellular and mitochondrial ROS fluorescence intensity(P<0.05),which was attenuated by AST(P<0.01).③ JC-1 assay revealed decreased mitochondrial membrane potential in OXA group(P<0.01),which was partially reversed by AST(P<0.05).④ Western blotting results showed that OXA upregulated Nrf2 and HO-1 expressions(P<0.05,P<0.01),and AST further enhanced their levels(P<0.01).Conclusion AST alleviates OXA-induced neuropathic pain by promoting Nrf2/HO-1 expression,enhancing SOD activity,reducing lipid peroxidation and ROS production,and improving mitochondrial function.
3.Effects of fluoxetine on neuronal autophagy and inflammatory response in rats with subarachnoid hemorrhage by regulating the CXCR4/NLRP1 pathway
Jialu XU ; Liu CUI ; Hongxin YANG ; Ruijuan LI
Journal of Chinese Physician 2025;27(11):1683-1689
Objective:To investigate the protective effect of fluoxetine on neurons in rats with subarachnoid hemorrhage (SAH) and explore its mechanism based on the chemokine receptor 4 (CXCR4)/nucleotide-binding oligomerization domain-like receptor protein 1 (NLRP1) pathway.Methods:Seventy-five rats were randomly divided into a normal control group and a model group. The SAH model was established by the internal carotid artery puncture method in the model group. After modeling, rats were randomly divided into the model group, fluoxetine low-, medium-, and high-dose groups, and nimodipine group, with 12 rats in each group. The fluoxetine low-, medium-, and high-dose groups were intravenously injected with fluoxetine at doses of 5, 10, and 15 mg/kg, respectively; the nimodipine group was intraperitoneally injected with nimodipine at 0.2 mg/kg; the normal control group and model group were intraperitoneally injected with an equal volume of normal saline, once a day for 7 consecutive days. The shuttle box was used to determine the number of avoidance responses and avoidance response time of rats. The water content of brain tissue and Evans blue exudation volume were calculated. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) in the hippocampal tissue. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of hippocampal tissue. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA levels of CXCR4 and NLRP1 in the hippocampal tissue. Western blot was used to determine the protein levels of CXCR4, NLRP1, LC3-Ⅱ, and Beclin1 in the hippocampal tissue.Results:Compared with the normal control group, the model group had a lower number of avoidance responses, lower levels of SOD, CAT, GSH, CXCR4 mRNA, CXCR4, LC3-Ⅱ, and Beclin1 protein in the hippocampal tissue (all P<0.05); while the avoidance response time, brain water content, Evans blue exudation volume, levels of IL-6, TNF-α, MDA, and mRNA and protein levels of NLRP1 in the hippocampal tissue were higher (all P<0.05). Compared with the model group, the fluoxetine groups (all doses) and nimodipine group had a higher number of avoidance responses, higher levels of SOD, CAT, GSH, CXCR4 mRNA, CXCR4, LC3-Ⅱ, and Beclin1 protein in the hippocampal tissue (all P<0.05); while the avoidance response time, brain water content, Evans blue exudation volume, levels of IL-6, TNF-α, MDA, and mRNA and protein levels of NLRP1 in the hippocampal tissue were lower (all P<0.05); moreover, the changes in various indicators were more significant with the increase of fluoxetine dose. HE staining results showed that there were no pathological changes in the hippocampal tissue of the normal control group; in the model group, the number of hippocampal neurons decreased, nuclei were pycnotic, and cell arrangement was irregular. Compared with the model group, the number of hippocampal neurons increased, cell arrangement was regular, and hippocampal pathology was significantly restored in the fluoxetine groups (all doses) and nimodipine group. Conclusions:Fluoxetine can significantly alleviate the pathological progression of cerebral edema, repair neuronal damage, improve neurological function, and regulate mitochondrial autophagy in SAH rats, whose mechanism may be related to the regulation of the CXCR4/NLRP1 pathway.
4.Application of Guided Care nursing model intervention in postoperative rehabilitation of total knee arthroplasty patients
Yingchao TANG ; Xuan WEI ; Ruijuan LI ; Fuxiao WANG ; Yanmei ZHENG
Chinese Journal of Modern Nursing 2025;31(17):2325-2329
Objective:To explore the impact of the Guided Care nursing model on exercise adherence and knee joint function recovery in patients after total knee arthroplasty (TKA) .Methods:A total of 106 TKA patients from Zhengzhou Orthopedic Hospital, selected by convenience sampling between January 2023 and January 2024, were randomly assigned to the observation group and the control group (53 patients in each group) . The control group received routine nursing care, while the observation group received Guided Care nursing model intervention in addition to the routine care. Exercise adherence (assessed using the Orthopedic Patients' Exercise Adherence Scale) , knee joint function recovery [assessed using the Hospital for Special Surgery Knee Score (HSS) and Range of Motion (ROM) ] , and postoperative complication rates were compared between the two groups.Results:After intervention, the observation group showed significantly higher total scores for exercise adherence, HSS scores, and ROM compared to the control group ( P<0.05) . Additionally, the total postoperative complication rate in the observation group was lower than that of the control group, with statistically significant difference ( P<0.05) . Conclusions:The Guided Care nursing model intervention effectively improves exercise adherence in TKA patients, accelerates knee joint function recovery, and reduces postoperative complications.
5.Effectiveness of multi-component exercise intervention in rehabilitative nursing of elderly patients with intertrochanteric femoral fractures and frailty
Ruijuan LI ; Yingchao TANG ; Ning ZHAO ; Wei SHEN ; Lan WEI
Chinese Journal of Modern Nursing 2025;31(16):2215-2220
Objective:To explore the efficacy of multi-component exercise intervention in the rehabilitation nursing of elderly patients with intertrochanteric femoral fractures and frailty.Methods:Between January and December 2023, 130 elderly patients with intertrochanteric femoral fractures and frailty admitted to Zhengzhou Orthopaedic Hospital were selected by convenience sampling method. The patients were divided into control group ( n=65) and observation group ( n=65) using the random number table method. Control group implemented conventional nursing and observation group was treated with multi-component exercise intervention, both intervening for three months. The rehabilitation status of two groups of patients was evaluated with the Modified Barthel Index (MBI) and Functional Independence Measure (FIM) . Harris Hip Score (HHS) , Physical Frailty Phenotype, Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and Compliance Scale of Functional Exercise for Orthopedic Patients were used to evaluate the hip function, frailty, quality of life and exercise compliance. Results:After intervention, the MBI score, FIM score and SF-36 score of control group were lower than those of observation group, and the Physical Frailty Phenotype score was higher than that of observation group, and the differences were statistically significant ( P<0.05) . At one and three months after intervention, the HHS scores of observation group were higher than those of control group, and the differences were statistically significant ( P<0.05) . During the intervention period, the exercise compliance of patients in observation group was higher than that of control group, and the difference was statistically significant ( P<0.05) . Conclusions:Multi-component exercise intervention promotes postoperative rehabilitation, improves hip function and quality of life, alleviates the frailty, and enhances exercise compliance in elderly patients with intertrochanteric femoral fractures and frailty.
6.Study on the influential factors for clinical efficacy of polymyxin B combined with other antibiotics in the treatment of carbapenem-resistant Acinetobacter baumannii pulmonary infection
Mei DU ; Ruijuan TAN ; Lidan WANG ; Hejun CHEN ; Hanze LI ; Yuanyuan ZHANG
China Pharmacy 2025;36(12):1495-1499
OBJECTIVE To analyze the influential factors for clinical efficacy of polymyxin B combined with other antibiotics in the treatment of carbapenem-resistant Acinetobacter baumannii(CRAB)pulmonary infection.METHODS A retrospective analysis was conducted on the clinical data of patients with CRAB pulmonary infection in our hospital from May 2021 to October 2024.Information such as age,gender,admitting department,infection status,underlying medical conditions,mechanical ventilation time,combination anti-infective treatment regimens,and the Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE-Ⅱ)score 24 h before medication was compiled.Based on the effectiveness of the treatment,patients were divided into treatment-effective group and treatment-ineffective group.Univariate analysis and multivariate Logistic regression analysis were employed to identify independent factors influencing clinical efficacy.RESULTS A total of 156 patients were included,and 108 patients were treated effectively,with an effective rate of 69.23%.The results of univariate analysis indicated that there were statistically significant differences between 2 groups in terms of the duration of mechanical ventilation time,APACHE-Ⅱ score 24 h before medication,the number of complication types,the proportion of abnormal coagulation function,anti-infective treatment course,and hospital stay before medication(P<0.05).The results of multivariate Logistic regression analysis showed that APACHE-Ⅱ score≥15 points 24 h before medication[OR=2.965,95%CI(1.284,6.845),P=0.020],mechanical ventilation time≥10 d[OR=3.577,95%CI(1.185,10.793),P=0.037]and hospital stay≥14 d before medication[OR=2.422,95%CI(1.036,5.654),P=0.041]were independent risk factors,and anti-infective treatment course>7 d was a protective factor[OR=0.445,95%CI(0.221,0.895),P=0.043].CONCLUSIONS This study shows that the effective rate of polymyxin B combined with other antibiotics in the treatment of CRAB pulmonary infection is less than 70%.The mechanical ventilation time≥10 d,APACHE-Ⅱ score≥15 points 24 h before medication,and hospital stay≥14 d before medication may lead to treatment failure,whereas anti-infective treatment course>7 d may be associated with treatment success.
7.The role of gut microbiota homeostasis in the occurrence and development of hepatocellular carcinoma and targeted intervention strategies
Yan CUI ; Junzhe JIAO ; Ruijuan YAN ; Shuguang YAN ; Hailiang WEI ; Zhanjie CHANG ; Haibo ZHANG ; Jingtao LI
Journal of Clinical Hepatology 2025;41(9):1913-1919
Hepatocellular carcinoma (HCC), as the sixth most common malignant tumor worldwide, poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota (GM) homeostasis in the development and progression of HCC, in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis, intestinal leakage, microbial-associated molecular pattern, bacterial translocation, and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape, thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC, deeply analyzes the mechanism of action of GM in the development and progression of HCC, investigates the role of bile acid-related metabolites, short-chain fatty acid-related metabolites, and other metabolites in HCC, and explores the strategies for targeting GM in the treatment of HCC, including probiotics, prebiotics, antibiotics, Toll-like receptor 4 antagonists, and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC, which provides a direction for developing new diagnosis and treatment strategies.
8.Exploration on the Mechanism of Kuijie Ankang Decoction in Treating Ulcerative Colitis Based on Immune,Autophagy and Intestinal Flora
Cong REN ; Fanyan MENG ; Yan GONG ; Lili TANG ; Ruijuan LUO ; Yizhen LI ; Shuang LI ; Chengcheng YUAN ; Yuedong LIU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(3):119-128
Objective To investigate the mechanism of Kuijie Ankang Decoction in regulating immune,autophagy and intestinal flora in the treatment of ulcerative colitis(UC).Methods UC mouse model was established by free drinking with sodium dextran sulfate.The mice were randomly divided into blank control group,model group,Kuijie Ankang Decoction group,salazine sulfopyridine(SASP)group and 3-methyladenine(3-MA)group,with 12 mice in each group.Each drug group was given corresponding drugs for gavage,the blank control group and model group were given the same volume of distilled water for gavage for 7 days.The general condition of mice was observed and the disease activity index(DAI)was scored,the morphology of colon tissue was observed by HE staining,the contents of TNF-α,IL-1β,IL-6,IL-8 and IL-10 in colon tissue were detected by ELISA,the mRNA and protein expressions of LC3,Beclin-1 and p62 in colon tissue were detected by RT-qPCR and Western blot,respectively.16S rDNA sequencing was used to analyze the structure of intestinal flora.Results Compared with the blank control group,the mice in the model group showed a decrease in body mass,an increase in DAI score,a decrease in colon length,serious mucosal injury and inflammatory cell infiltration,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue significantly increased(P<0.05,P<0.01),the content of IL-10 decreased(P<0.01),the mRNA expressions of LC3 and Beclin-1 in colon tissue decreased(P<0.05,P<0.01),the mRNA and protein expression of p62 increased(P<0.01),while the expressions of LC3Ⅱ/LC3Ⅰ and Beclin-1 proteins decreased(P<0.05,P<0.01).Compared with the model group,the body mass of mice in Kuijie Ankang Decoction group and SASP group increased(P<0.05),DAI score decreased(P<0.05),the colon length increased(P<0.05),the pathological damage of colon mucosa was alleviated,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue decreased(P<0.05,P<0.01),the content of IL-10 increased(P<0.01),the expressions of LC3 and Beclin-1 mRNA in colon tissue increased(P<0.05,P<0.01),the expression of p62 mRNA and protein decreased(P<0.05,P<0.01),the expressions of LC3Ⅱ/LC3Ⅰand Beclin-1 protein increased(P<0.05,P<0.01).16S rDNA sequencing results showed that the diversity and evenness of the intestinal flora in the model group mice decreased,with a decrease in the relative abundance of Firmicutes,Actinobacteria and Patescibacteria(P<0.05),and an increase in the relative abundance of Bacteroidota,Verrucomicrobiota and Proteobacteria(P<0.05);the relative abundance of Bacilli and Coriobacteriia decreased(P<0.05),the relative abundance of Bacteroidia,Clostridia and Verrucomicrobiae increased(P<0.05);the relative abundance of Ligilactobacillus and Dubosiella decreased(P<0.05),the relative abundance of unclassified Muribaculaceae,Lachnospiraceae NK4A136_group,Akkermansia and unclassified Lachnospiraceae increased(P<0.05).Compared with the model group,the diversity and evenness of intestinal flora increased in Kuijie Ankang Decoction group and SASP group,with an increase in the relative abundance of Firmicutes(P<0.05),a decrease in the relative abundance of Bacteroidota and Verrucomicrobiota(P<0.05),the relative abundance of Bacteroidia and Bacilli increased(P<0.05),the relative abundance of Verrucomicrobiae decreased(P<0.05);the relative abundance of unclassified Muribaculaceae and Ligilactobacillus increased(P<0.05),while the relative abundance of Lachnospiraceae NK4A136_group and Akkermansia decreased(P<0.05).Conclusion Kuijie Ankang Decoction can significantly improve the intestinal mucosal injury of UC mice,and the mechanism may be related to the regulation of colon autophagy level and intestinal flora disorder.
9.Inhibitory effect of safranal on proliferation,migration and phenotypic transformation of vascular smooth muscle cells of rats induced by high glucose in vitro
Yixuan GAO ; Peng WANG ; Silong ZHANG ; Ruijuan GAO ; Yingfang MA ; Keke ZHANG ; Dan FENG ; Zongqi HUANG ; Ketao MA ; Li LI ; Junqiang SI
Journal of Jilin University(Medicine Edition) 2025;51(4):948-957
Objective:To discuss whether safranal affects the proliferation,migration,and phenotypic transformation of the vascular smooth muscle cells(VSMCs)in a high-glucose environment and to clarify the function of safranal in the prevention and treatment of diabetic(DM)vascular complications.Methods:The SD rats were selected as experimental subjects;primary VSMCs were cultured from rat thoracic aortas and divided into control group,25 mmol·L-1 high glucose(HG)group,HG+20 μmol·L-1 safranal group,HG+40 μmol·L-1 safranal group,and HG+80 μmol·L-1 safranal group.The cells in control group received no treatment;the cells in 25 mmol·L-1 HG group were pretreated with 25 mmol·L-1 HG;the cells in HG+20,40,and 80 μmol·L-1 safranal groups were further treated with 20,40,and 80 μmol·L-1 safranal respectively for 48 h on the basis of 25 mmol·L-1 HG group.Cell counting kit-8(CCK-8)method was used to determine the appropriate concentration of safranal and detect the viabilities of the VSMCs in various groups;cell scratch healing assay was used to detect the scratch healing rates of the VSMCs in various groups;Transwell chamber assay was used to detect the numbers of the migration VSMCs in various groups;immunofluorescence method was used to detect the fluorescence intensities of alpha-smooth muscle actin(α-SMA)and rabbit anti-osteopontin(OPN)in the VSMCs in various groups;Western blotting method was used to detect the expression levels of OPN,α-SMA,and proliferating cell nuclear antigen(PCNA)in the VSMCs in various groups.Results:Under microscope,on the 4th day of in vitro culture,the spindle-shaped or triangular cells crawled out from the edge of the thoracic aorta tissue blocks,with long spindle being the most common morphology.On the 14th,the cells gradually covered the bottom of the dish;when cell density reached 80%-90%,the characteristic"hills and valleys"growth pattern appeared.Third-generation cells were taken for immunofluorescence identification;immunofluorescence staining with VSMC-specific marker α-SMA showed positive expression of α-SMA protein in the primarily cultured VSMCs.The CCK-8 assay results showed that compared with control group,the cell viability of the cells in 160 μmol·L-1 safranal group was significantly decreased(P<0.01),indicating toxic damage to the cells.Under the conditions of safranal concentrations at 20,40,and 80 μmol·L-1 respectively,after 48 h intervention on VSMCs,no significant adverse effect on cell viability was observed;considering both the effect and toxicity of safranal,these three concentrations were used in subsequent cell experiments.After 48 h intervention,compared with control group,the activity of the VSMCs in 25 mmol·L-1 HG group was increased(P<0.001);compared with 25 mmol·L-1 HG group,the activities of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05).The cell scratch healing assay and Transwell assay results showed that after 48 h intervention,the scratch healing rate of the VSMCs in 25 mmol·L-1 HG group was significantly higher than that in control group(P<0.01),and the number of transmembrane cells through the Transwell chamber was significantly increased(P<0.05);compared with 25 mmol·L-1 HG group,the scratch healing rates of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05),and the number of transmembrane cells was decreased(P<0.05).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was significantly weakened(P<0.001),while the fluorescence intensity of OPN protein was significantly enhanced(P<0.001);compared with 25 mmol·L-1 HG group,the fluorescence intensities of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually increased(P<0.05),and the fluorescence intensities of OPN were gradually weakened(P<0.05).The Western blotting method results showed that compared with control group,the expression level of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was decreased(P<0.05),and the expression levels of PCNA and OPN proteins were increased(P<0.01);compared with 25 mmol·L-1 HG group,the expression level of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were increased(P<0.05),and the expression levels of PCNA and OPN proteins were decreased(P<0.05).Conclusion:Safranal can inhibit the proliferation,migration,and phenotypic transformation of the VSMCs induced by high glucose.
10.WW domain-containing ubiquitin E3 ligase 1 regulates immune infiltration in tumor microenvironment of ovarian cancer.
Xiaojuan GUO ; Ruijuan DU ; Liping CHEN ; Kelei GUO ; Biao ZHOU ; Hua BIAN ; Li HAN
Journal of Southern Medical University 2025;45(5):1063-1073
OBJECTIVES:
To explore the association of the expression of WW domain-containing ubiquitin E3 ligase 1 (WWP1) with immune infiltration in tumor microenvironment (TME) of ovarian cancer.
METHODS:
Ovarian cancer patient data from The Cancer Genome Atlas (TCGA) were used to analyze the association of WWP1 expression with patient prognosis. TISCH2 was utilized to analyze the changes in immune cell subtypes in TME of metastatic tumor and after chemotherapy. The impact of WWP1 on immune cell infiltration, somatic copy number alterations of WWP1 and evolution of immune cell subtypes was evaluated using TIMER and TIGER pseudo-time analysis. A deep learning model was used to analyze TCGA pathological images to investigate the effect of WWP1 on TME of ovarian cancer. RNA-seq analysis was conducted to identify the differentially expressed genes in WWP1-overexpressing SKOV3 cells and validate immune infiltration. Multicolor immunofluorescence assay was used to analyze the immune markers in SKOV3 and SKOV3/DDP cell xenografts in nude mice.
RESULTS:
The patients with high WWP1 expression levels had significantly lower overall survival rate (P=0.0012). High WWP1 expression levels and Stage IV disease were both associated with a poor prognosis (P<0.05). In metastatic ovarian cancer or after chemotherapy, the percentages of malignant tumor cells and tumor-associated fibroblasts increased in the TME, accompanied by elevated WWP1 levels. WWP1 expression level was positively correlated with pro-tumorigenic immunosuppressive cells (r=0.1323-0.3955, P<0.05) and negatively with tumor-inhibiting immune cells (r=-0.1949- -0.1333, P<0.05). Specific copy number alterations of WWP1 also influenced CD8+ T cell percentage and neutrophil infiltration levels in the TME. RNA-seq analysis of WWP1-overexpressing SKOV3 cells and immunofluorescence assay of the tumor-bearing mice yielded findings consistent with those of bioinformatics analysis.
CONCLUSIONS
WWP1 may serve as a prognostic biomarker and a potential target for immune regulation in the TME of ovarian cancer.
Female
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Ovarian Neoplasms/genetics*
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Humans
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Ubiquitin-Protein Ligases/metabolism*
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Tumor Microenvironment/immunology*
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Animals
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Mice
;
Cell Line, Tumor
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Mice, Nude
;
Prognosis
;
Gene Expression Regulation, Neoplastic

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