1.Mechanism of Piezo-type mechanosensitive ion channel component 1 in rat pressure injury
Jiaqi SUN ; Lu BIAN ; Wentao SHI ; Xuechao WU ; Xiaojie LU
Chinese Journal of Tissue Engineering Research 2025;29(8):1578-1584
BACKGROUND:The mechanisms underlying the occurrence of pressure injuries are complex,and it is not entirely clear which factors play a central role in the development of pressure injuries and how these factors operate. OBJECTIVE:To investigate the relationship between Piezo-type mechanosensitive ion channel component 1(Piezo1)and the occurrence of pressure injuries. METHODS:(1)Cellular experiment:Human immortalized keratinocytes(HaCaT)were treated with Yoda1,a Piezo1 agonist,at different concentrations.Cell viability,calcium ion influx,Piezo1,and apoptosis-related protein expression were detected.(2)Animal experiment:Twelve Sprague-Dawley rats were randomly divided into a control group and three experimental groups,with three rats in each group.The control group was not subjected to pressure,while in the three experimental groups,magnets with a thickness of 1,2,and 3 mm were used to press on both sides of the rats'back for 1 hour,respectively,to establish the animal models of pressure injuries.After modeling,all traumatic tissues were excised and subjected to hematoxylin-eosin,Masson,immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION:Cellular experiments:The results of live/dead cell staining showed that HaCaT cell apoptosis increased with the increase of Yoda1 concentration(0,2.5,5,and 10 μmol/L),and calcium ion influx increased with the increase of Yoda1 concentration(0,5,and 10 μmol/L),as well as with the prolongation of treatment time.Western blot assay results showed an increase in the expression of BAX,TG2,and PIEZO1 and a decrease in the expression of the expression of Bcl-2 protein in HaCaT cells in 5 and 10 μmol/L Yoda1 groups compared with the control group(0 μmol/L Yoda1).Animal experiments:The results of hematoxylin-eosin and Masson staining showed that the skin structure of the three experimental groups was damaged at the compression site,there was subcutaneous fat liquefaction and necrosis,and collagen was sparse and disorganized,and damage to the skin structure at the compression site was aggravated with the increase of magnet thickness.Immunofluorescence staining and western blot results showed that compared with the control group,the expression of BAX,TG2,Yap1 and PIEZO1 proteins was elevated,and the expression of Bcl-2 proteins was lowered in the three experimental groups.Moreover,the expression of related proteins showed more significant changes with the increase of magnet thickness(pressure).To conclude,skin compression activates PIEZO1,leading to a significant influx of calcium ions.As the pressure increases,this ultimately results in cell apoptosis due to calcium overload.
2.Study on relationships of MS4A1 gene polymorphism with blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma
Feng SHI ; Tao LIU ; He HUANG ; Caifu FANG ; Shaoxing GUAN ; Zhang ZHANG ; Zhao WANG ; Xiaojie FANG ; Zhuojia CHEN ; Shu LIU
China Pharmacy 2025;36(13):1641-1647
OBJECTIVE To explore the effects of CD20 coding gene (MS4A1) polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020, with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software, including rs1051461, rs17155034, rs4939364, and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors(demographic, clinical, and genotypic variables) in patients and the steady-state trough concentration of rituximab during the first course of treatment, followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival (PFS) and overall survival (OS). Using MS4A1 genotype and tumor stage as independent variables, Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL,which was significantly lower than 21.95 μg/mL in AA+AC carriers (P<0.05). The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers, CT+TT carriers had significantly prolonged PFS and OS (P<0.05). The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype (HR=4.406, 95%CI:1.743-11.137, P<0.05) and tumor Ⅲ&Ⅳ (HR=3.233, 95%CI: 1.413-7.399, P<0.05) were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab, and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.
3.Role of ferritinophagy in the pathogenesis of diabetes and its complications:A review of literature
Jianmei SHI ; Xixi WANG ; Xiaojie WEI
The Journal of Practical Medicine 2024;40(3):417-422,427
Diabetes mellitus(DM)is a common metabolic disease,and its hyperglycemia can induce many complications and even threaten human health and life.Ferritinophagy,currently a research focus,has been proven to be related to the occurrence and development of DM and its complications.Ferritinophagy,which is cell-selective,is mediated by nuclear receptor coactivator 4(NCOA4),which degrades ferritin in autophagosomes and releases excessive iron ions so that irons are overloaded and ROS are accumulated.This process contributes to the upstream ferroptosis.This article reviews the mechanism of ferritinophagy and its pathogenesis in DM and its complications,and further analyzes the effects of regulated ferritinophagy on DM and its complications,pro-viding new insight into the prevention and treatment of DM and its complications.
4.Inhibitory Effect of Curcumin and Its Derivatives on TGF-β Induced Fibrosis of LX-2 Cells
Yidan SHAO ; Tingting SHI ; Yanmei ZHAO ; Xi ZOU ; Jianjun XI ; Jing ZHANG ; Xiaojie JIANG ; Rangxiao ZHUANG
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1750-1757
OBJECTIVE
To study the inhibitory effect and mechanism of curcumin and its derivatives A and B on TGF-β induced LX-2 cell fibrosis.
METHODS
Established the liver fibrosis model of LX-2 cells induced by TGF-β(10 ng·mL−1).The effects on cell proliferation were detected by CCK-8. The effects on cell apoptosis was detected by flow cytometry. The effects on fibrosis related factors(Collagen I, Collagen Ⅳ, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, MMP2, MMP9, TIMP1 and TIMP2) protein expression and gene transcription levels were detected by Western blotting and q-PCR.
RESULTS
The curcumin and its derivative A and B had the inhibition effects on normal LX-2 cells, and the IC25 values were 15.7, 2.6, 10.2 μmol·L−1, respectively. Compared to the model group, the curcumin(15.7 μmol·L−1) and its derivative A(2.6 μmol·L−1) and B(10.2 μmol·L−1) had the significant inhibition effects on cell proliferation of the TGF-β induced LX-2 cells(P<0.05). The cell apoptosis rate of curcumin derivative B group was higher than the model group(P<0.05). Collagen I, Fibronectin, Vimentin, α-SMA, TGFβR1 and TIMP-1 protein expression levels in curcumin group were lower, while the protein expression level of MMP-9 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, TIMP-1 and TIMP-2 in curcumin derivative A group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, TIMP-1 and TIMP-2 in curcumin derivative B group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The gene transcription levels of Collagen I, Fibronectin, α-SMA and TIMP-1 in curcumin group were lower(P<0.05). The gene transcription levels of Collagen I, Fibronectin and α-SMA in curcumin derivative A and B groups were lower(P<0.05).
CONCLUSION
Curcumin and its derivatives A and B inhibit the abnormal activation and proliferation of TGF-β-induced LX-2 cells, inhibit the excessive secretion and accumulation of its extracellular matrix components, and promote its degradation, thus playing an anti-fibrotic effect in vitro, especially the curcumin derivative B.
5.Toxic effects of sodium hypochlorite as disinfectants on human bronchial epithelial cells
Jiawei LI ; Jiangzheng LIU ; Xiaojie GUO ; Yongmei TU ; Minjie SHI ; Wenli LI ; Jinsuo LU
Journal of Environmental and Occupational Medicine 2024;41(7):822-827
Background There are a variety of microorganisms in ambient air, and susceptible people can be infected once contact with pathogenic microorganisms in the environment. In order to avoid the spread of pathogenic bacteria, disinfection is the simplest and most effective way of killing pathogenic bacteria in the environment to block the contact between pathogenic bacteria and humans. Sodium hypochlorite (NaClO) is the most widely used disinfectant, but its safety in ambient air disinfection is not clear yet. Objective To establish a model of bronchial epithelial cell (BEAS-2B) injury induced by NaClO, and to explore the mechanism of the toxic effect of NaClO disinfectants on BEAS-2B. Methods Cells were treated with concentration gradients of 0, 25, 50,100, 200, and 400 μmol·L−1 of the diluted NaClO (100 mmol·L−1) standard solution, respectively, and cell activity was measured by cell counting kit-8 (CCK-8) assay after 15 and 30 min. Cells treated with 0, 25, and 50 μmol·L−1 NaClO were selected to observe the cell morphology under an inverted microscope, apoptosis was determined by flow cytometry Annexin V FITC / PI double staining to determine the final experimental concentration. The morphology of organelles such as mitochondria was observed under a transmission electron microscope. Mitochondrial membrane potential of the cells was detected by JC-1 staining. Intracellular Ca2+ concentration was measured with a Fluo-4 AM fluorescent probe. Total cellular reactive oxygen species (ROS) was detected with a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe, cell mitochondrial ROS with a dihydroethidium (DHE) fluorescent probe, and lipid peroxidation intermediate malondialdehyde (MDA) with a commercial kit. Results Compared with 0 μmol·L−1, NaClO treatment group, cell morphology did not change a lot after 25 μmol·L−1 NaClO treatment for 30 min, and the cells began to wrinkle and become round after 30 min treatment with 50 μmol·L−1 NaClO, showing about 70% of normal cell viability (P<0.01). So 30 min 50 μmol·L−1 NaClO treatment was selected for the subsequent experiment. The experimental results found that compared with the 0 μmol·L−1 NaClO treatment group, the number of apoptotic cells increased (P<0.05), the mitochondrial membrane potential decreased (P<0.01), the intracellular Ca2+ concentration increased (P<0.05), the cellular ROS level increased (P<0.05), the mitochondrial ROS level increased (P<0.01), and the MDA content increased (P<0.01) in the NaClO treatment group.. Conclusion The study has successfully established a model of BEAS-2B injury induced by NaClO, and found that NaClO can lead to cell damage by inducing apoptosis and oxidative stress in BEAS-2B cells. According to the results, there are two possible reasons. First, NaClO solves in water to form hypochlorous acid (HClO) which is oxidative and increases the intracellular ROS level after entering cells, leading to cellular oxidative stress. Second, HClO enters cells to directly attack the mitochondrial membrane, resulting in the imbalance of potential inside and outside the mitochondrial membrane, and apoptosis caused by Ca2+ efflux.
6.Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China
Yufei LUO ; Yuan WEI ; Xiaochen WANG ; Yi ZHANG ; Wenli ZHANG ; Bing WU ; Zhengxiong YANG ; Xiaojie DONG ; Ruiting HAO ; Yifu LU ; Xiaoshuang FU ; Ziyue ZHU ; Ying ZHU ; Yuebin LYU ; Dongqun XU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2024;58(6):839-846
Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.
7.A panel study on the association of organophosphate ester flame retardant exposure with thyroid function related hormones in healthy older adults
Chenfeng LI ; Yibo XU ; Peijie SUN ; Enmin DING ; Chenlong LI ; Xiaojie GUO ; Jiran ZHANG ; Song TANG ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2024;58(6):847-856
Objective:To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults.Methods:In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T 3), and thyroxine (T 4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results:Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M ( Q 1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M ( Q 1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M ( Q 1, Q3) for TSH, T 3, and T 4 was 3.74 (2.55, 5.69) μIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95% CI:-15.17%, -4.36%) and 11.14% (95% CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion:Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.
8.Progress in research on risk assessment models for cancer-associated thrombosis
Haoran SHI ; Qiaodan LU ; Yuan XU ; Xiaojie WANG ; Haibo DENG ; Lei WANG ; Jianhua SUN ; Yu WANG ; Liyun ZHU ; Ranxun AN ; Xinyi ZHOU ; Yufen MA
Chinese Journal of Modern Nursing 2024;30(8):1010-1017
Cancer-associated thrombosis (CAT) is a common complication and cause of death in cancer patients. Accurately and efficiently identifying high-risk groups for CAT using risk assessment models and implementing targeted early prevention is key. Although numerous CAT risk assessment models currently exist, their predictive capabilities vary across different populations. This article provides a comprehensive review of CAT risk assessment models and their application status, aiming to offer a reference for clinical nursing staff to understand and choose appropriate risk assessment tools.
9.Development of the Cancer-associated Thrombosis Prevention Knowledge, Attitude and Practice Questionnaire for Nurses and its reliability and validity tests
Haoran SHI ; Yuan XU ; Xiaojie WANG ; Haibo DENG ; Lei WANG ; Jianhua SUN ; Yu WANG ; Liyun ZHU ; Qiaodan LU ; Ranxun AN ; Xinyi ZHOU ; Yufen MA
Chinese Journal of Modern Nursing 2024;30(16):2124-2130
Objective:To develop the Cancer-associated Thrombosis (CAT) Prevention Knowledge, Attitude and Practice Questionnaire for Nurses, and conduct reliability and validity tests.Methods:This study was a questionnaire development study. Guided by the theory of knowledge, attitude, and practice, an initial CAT Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses was formed through literature review, group discussion, two rounds of expert consultation, and pre-survey. From April to May 2023, convenience sampling was used to select 700 in-service nurses from Chinese Academy of Medical Sciences & Peking Union Medical College as the research subject, and the reliability and validity of the questionnaire were tested.Results:A total of 700 questionnaires were distributed, and 593 valid questionnaires were collected, with a valid response rate of 84.71% (593/700). The final version of the CAT Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses included three dimensions of knowledge, attitude, and practice, with a total of 39 items. The scale-level content validity index ( S- CVI) was 1.000, with an average S- CVI of 0.971 and an item-level CVI (I- CVI) of 0.860 to 1.000. Exploratory factor analysis extracted a total of seven common factors, with a cumulative variance contribution rate of 77.376%. The total Cronbach's α coefficient of the questionnaire was 0.937, and the Cronbach's α coefficients for each dimension were 0.923, 0.987, and 0.979. The half reliability coefficient was 0.984. After two weeks, the reliability coefficients for each dimension of retesting were 0.959, 1.000, and 0.994. Conclusions:The CAT Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses developed in this study has good reliability and validity, and can be used as an evaluation tool for the cognition of clinical nurses in CAT prevention.
10.Cognition and training needs of emergency response teamwork skills among nursing undergraduates: a qualitative study
Dan WEI ; Xinjuan WU ; Xiaojie WANG ; Jie CHEN ; Dongying ZHANG ; Meng ZHANG ; Jialu ZHANG ; Di SHI ; Hongbo LUO ; Hongyan LI ; Wei WANG ; Xiaoying LIANG ; Tianyi WANG ; Ning ZHANG ; Haixin BO
Chinese Journal of Modern Nursing 2024;30(33):4520-4525
Objective:To gain a deep understanding of the current cognition and training needs of nursing undergraduates regarding their emergency response teamwork skills, and to provide reference for the development of courses on emergency response teamwork among nursing undergraduates.Methods:From September to October 2023, purposive sampling was used to select 15 senior nursing undergraduates from Peking Union Medical College, Beijing University of Chinese Medicine, and Beijing City University as subjects for semi-structured interviews. Colazizzi 7-step analysis method was used to summarize and extract themes.Results:Three themes were extracted, including insufficient cognition and skill in emergency response, lack of emergency response teamwork cultivation, and the need for systematic and comprehensive training courses.Conclusions:Universities, hospitals, and other training institutions should work together to develop a systematic emergency response teamwork training course for nursing undergraduates, to cultivate the skills of nursing undergraduates and reserve talents for high-quality emergency response nursing teams.


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