1.Construction and validation of a novel prognostic risk scoring table for patients with acute-on-chronic liver failure
Zhanhu BI ; Haifeng HU ; Hong DU ; Linxu WANG ; Xiaofei YANG ; Yidi DING ; Jianqi LIAN
Journal of Clinical Hepatology 2025;41(10):2102-2109
ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure (ACLF), and to construct a risk scoring table that can accurately predict the prognosis of patients in the early stage. MethodsA retrospective analysis was performed for the clinical data of 502 patients with ACLF who were admitted to Tangdu Hospital, Air Force Medical University, from January 1, 2010 to December 31, 2020 (training set), and the influencing factors for 28-day mortality rate were identified. The 69 ACLF patients who were admitted to Tangdu Hospital, Air Force Medical University, from January 1 to December 31, 2021 were enrolled as the validation set. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A univariate Cox regression analysis was used to obtain the early warning indicators associated with the 28-day prognosis of ACLF patients, and variance inflation factors were used to assess multicollinearity among predictors; a multivariate Cox regression analysis was used to construct a risk model for ACLF prognosis (mortality). A risk scoring table for ACLF prognosis (mortality) was developed based on regression coefficients (β) from the model equation and weight assignments in the nomogram. Internal validation and comparison were performed for the risk model for ACLF prognosis (mortality), the scoring table for ACLF prognosis (mortality), and other scoring models (Child-Turcotte-Pugh [CTP] score, Model for End-Stage Liver Disease [MELD] score, MELD combined with serum sodium concentration [MELD-Na] score, and integrated MELD [iMELD] score) in the training set, while external validation and comprehensive evaluation of the scoring table and the other scoring models were performed in the validation set. The Nagelkerke’s R2 test and the Hosmer-Lemeshow test were used to assess the degree of fitting of the risk model for ACLF prognosis (mortality), the scoring table for ACLF prognosis (mortality), and other scoring models, and fitting curves were plotted. C-index was used to assess the discriminatory ability of the scoring table for ACLF prognosis (mortality) and the other scoring models, and the Z-test was used for comparison of C-index between different models. The decision curve analysis was used to compare the clinical benefits of the scoring table for ACLF prognosis (mortality) and the other scoring models. ResultsThe multivariate Cox regression analysis showed that age (hazard ratio [HR]=1.027, 95% confidence interval [CI]: 1.015 — 1.039, P<0.001), hepatic encephalopathy grade (grade 1: HR=2.928, 95%CI: 1.463 — 5.858, P=0.002; grade 2: HR=3.811, 95%CI: 2.078 — 6.988, P<0.001; grade 3: HR=3.916, 95%CI: 1.917 — 8.001, P<0.001; grade 4: HR=6.966, 95%CI: 4.559 — 10.644, P<0.001), an increase in total bilirubin (TBil) by ≥17.1 μmol/L per day (HR=1.771, 95%CI: 1.248 — 2.513, P=0.001), creatinine (HR=1.005, 95%CI: 1.004 — 1.006, P<0.001), neutrophil count (HR=1.092, 95%CI: 1.060 — 1.126, P<0.001), and international normalized ratio (HR=1.298, 95%CI: 1.187 — 1.418, P<0.001) were independent risk factors associated with the 28-day mortality rate of ACLF patients, and a risk scoring table was constructed for ACLF prognosis (mortality). The Nagelkerke’s R2 test showed that the risk scoring table for ACLF prognosis (mortality) had an R2 value of 0.599 in the training set and 0.722 in the validation set, which were higher than the R2 values of CTP, MELD, MELD-Na, and iMELD scores. The Hosmer-Lemeshow test showed that the risk scoring table for ACLF prognosis (mortality) had a P value of 0.280 in the training set and 0.788 in the validation set. The C-index analysis showed that the scoring table had a higher C-index than the other scoring models in the validation set (all P<0.001), as well as a higher C-index than CTP score in the training set (P<0.001). The decision curve analysis showed that the risk scoring table for ACLF prognosis (mortality) had higher clinical net benefits than the other scoring models. ConclusionCompared with other scoring models currently used in clinical practice, the novel risk scoring table for ACLF prognosis (mortality) constructed based on the six predictive factors of age, hepatic encephalopathy grade, an increase in TBil by ≥17.1 μmol/L per day, creatinine, neutrophil count, and international normalized ratio has a relatively high value in predicting the 28-day prognosis of ACLF patients.
2.The application progress of artificial intelligence technology in the diagnosis and treatment of developmental dysplasia of the hip
Zongwang SHEN ; Shijie LIAO ; Xiaofei DING ; Xiudong LI ; Jinmin ZHAO
Chinese Journal of Orthopaedics 2024;44(5):329-335
Developmental dysplasia of the hip (DDH) is a developmental disease with abnormal position and morphology of the acetabulum and femoral head. DDH ranges from mild dysplasia to complete dislocation, including simple acetabular dysplasia, subluxation, and total dislocation. DDH is one of the most common hip diseases in children, and its onset begins in infancy. The anatomical structure of the hip joint is complex, and there are some practical problems in the large -scale clinical diagnosis and screening work, such as heavy workload, high misdiagnosis rate and missed diagnosis rate, and a long learning period of surgery. Artificial intelligence (AI) is an emerging technology science used to research and develop theories, methods, technologies and application systems that can simulate human intelligence. The main goal is to enable machines to complete complex tasks that require human intelligence. At present, artificial intelligence is mainly used in the diagnosis and treatment of DDH. Artificial intelligence combined with X-ray or ultrasound is used to diagnose and screen DDH, which avoids subjectivity to a certain extent and improves the accuracy of diagnosis and screening. In the preoperative planning of periacetabular osteotomy and total hip arthroplasty, it can more accurately track the position of the bone block and design the size of the prosthesis, which makes the surgical planning more accurate to a certain extent. Artificial intelligence technologies such as 3D navigation system, surgical robot and robotic arm are helpful to improve the accuracy and safety of surgery. Artificial intelligence has the characteristics of simplicity, speed, high repeatability and deep learning ability, which to a certain extent saves manpower, material resources and time costs for DDH diagnosis and treatment, facilitates medical workers to share DDH diagnosis and treatment experience and reduces the burden of patients, families, society and the country. The application of artificial intelligence in DDH diagnosis and treatment is becoming more and more extensive, but at present, artificial intelligence in DDH screening is still in its preliminary stage. There are few reports on artificial intelligence technology in DDH hip preservation treatment and other surgical methods, and there is insufficient research on artificial intelligence in DDH conservative treatment, postoperative complications and prognosis prediction. It is worth exploring new ideas by researchers. At present, the application of artificial intelligence in DDH still has certain limitations, including problems such as difficult to control the quality of image data, difficult to develop and promote technology, and lack of laws and regulations. Based on the literature database and relevant data sharing network, this paper reviews the application of artificial intelligence in the diagnosis and treatment of DDH at home and abroad in recent years, summarizes the current application status of artificial intelligence in the diagnosis and treatment of DDH, and provides new ideas for the future application of artificial intelligence in the diagnosis and treatment of DDH.
3.Clinical features and early warning indicators of patients with acute-on-chronic liver failure and bacterial infection
Zhanhu BI ; Linxu WANG ; Haifeng HU ; Hong DU ; Yidi DING ; Xiaofei YANG ; Jiayi ZHAN ; Fei HU ; Denghui YU ; Hongkai XU ; Jianqi LIAN
Journal of Clinical Hepatology 2024;40(4):760-766
ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure (ACLF) and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1, 2010 to December 31, 2021, and according to the drug susceptibility results, the patients were divided into multidrug-resistant (MDR) bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic (ROC) curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection, sputum (27.7%) was the most common specimen for detection, followed by blood (24.6%), urine (18.5%), and ascites (17.7%). Bacterial infections were dominated by Gram-negative bacteria (58.5%). Of all bacteria, Escherichia coli (18.5%), Klebsiella pneumoniae (14.6%), and Enterococcus faecium (13.8%) were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin (72.2%), penicillin (57.4%), ampicillin (55.6%), and ciprofloxacin (53.7%), while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin (73.3%), cefazolin (50.0%), and cefepime (47.4%). The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection (61.5%). Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection, the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase (Z=2.089, P=0.037), aspartate aminotransferase (Z=2.063, P=0.039), white blood cell count (Z=2.207, P=0.027), and monocyte count (Z=4.413, P<0.001). The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection (odds ratio=7.120, 95% confidence interval [CI]: 2.478 — 20.456,P<0.001) and had an area under the ROC curve of 0.686 (95%CI: 0.597 — 0.776) in predicting ACLF with MDR bacterial infection(P<0.001), with the optimal cut-off value of 0.50×109/L, a sensitivity of 0.725, and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria, with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.
4.Incidence and risk factors of deep vein thrombosis in patients with rheumatoid arthritis
Xiaofei TANG ; Yonghong LI ; Qiuling DING ; Zhuo SUN ; Yang ZHANG ; Yumei WANG ; Meiyi TIAN ; Jian LIU
Journal of Peking University(Health Sciences) 2024;56(2):279-283
Objective:To investigate the incidence and risk factors of deep vein thrombosis(DVT)in patients with rheumatoid arthritis(RA).Methods:The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed,including demographic characteristics,concomitant diseases,laboratory examinations(blood routine,biochemistry,coagulation,inflammatory markers,rheumatoid factor,antiphospholipid antibodies and lupus anticoagulant,etc.)and treatment regimens.The patients were compared according to the presence or absence of DVT,and the t test,Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT,followed by Logistic regres-sion analysis to determine risk factors for DVT in patients with RA.Results:The incidence of DVT in the RA patients was 9.6%(31/322);the median age of RA in DVT group was significantly older than that in non-DVT group[64(54,71)years vs.50(25,75)years,P<0.001];the level of disease activity score using 28 joints(DAS28)-erythrocyte sedimentation rate(ESR)in DVT group was higher than that in non-DVT group[5.2(4.5,6.7)vs.4.5(4.5,5.0),P<0.001];the incidence of hypertension,chronic kidney disease,fracture or surgery history within 3 months,and varicose veins of the lower ex-tremities in DVT group was higher than that in non-DVT group(P<0.001).The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group(P=0.009,P=0.004),while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group(P<0.001).The use rate of glucocorticoid in DVT group was higher than that in non-DVT group(P=0.009).Logistic regression analysis showed that the age(OR=1.093,P<0.001),chronic kidney disease(OR=7.955,P=0.005),fracture or surgery history with-in 3 months(OR=34.658,P=0.002),DAS28-ESR(OR=1.475,P=0.009),and the use of glu-cocorticoid(OR=5.916,P=0.003)were independent risk factors for DVT in RA patients.Conclu-sion:The incidence of DVT in hospitalized RA patients was significantly increased,in addition to tradi-tional factors,such as age and chronic kidney disease,increased DAS28-ESR level and the use of glu-cocorticoid were also independent risk factors for DVT.
5.Extracellular vesicles carrying non-coding RNA regulate the activation of osteoclasts
Jianhong LIU ; Shijie LIAO ; Boxiang LI ; Shengping TANG ; Zhendi WEI ; Xiaofei DING
Chinese Journal of Tissue Engineering Research 2024;28(7):1076-1082
BACKGROUND:It has been demonstrated that osteoclast activation plays an important role in skeletal system-related diseases.The mechanism of regulation of osteoclast activation by extracellular vesicles carrying non-coding RNA has not been fully elucidated. OBJECTIVE:To review and summarize relevant literature in and outside China,and to review the regulation of osteoclast activation by different non-coding RNAs in extracellular vesicles in different diseases,so as to provide a certain direction for subsequent research. METHODS:"Non-coding RNA,miRNA,lncRNA,circRNA,snoRNA,osteoclasts,extracellular vesicles,exosome,microparticle,apoptotic bodies"were used as search terms to search the databases of CNKI,WanFang,and VIP."Extracellular vesicles,exosome,microparticle,apoptotic bodies,non-coding RNA,miRNA,lncRNA,circRNA,snoRNA,osteoclast"were used as search terms to search PubMed.Finally,71 articles were included. RESULTS AND CONCLUSION:(1)The activation of osteoclasts is affected by many factors,among which the specific mechanism of non-coding RNA regulating osteoclast activation is not clear.(2)Extracellular vesicles can be secreted by osteoblasts,bone marrow mesenchymal stem cells,tumor cells and other cells.As a carrier of intercellular communication,extracellular vesicles can carry non-coding RNA to regulate osteoclast activation.(3)In the current studies on the regulation of osteoclast activation by extracellular vesicles carrying non-coding RNA,most of the diseases are osteoporosis,followed by tumor bone metastasis,and most types of non-coding RNA are miRNA.(4)There are relatively few studies on the regulation of extracellular vesicles carrying lncRNA and circRNA and snoRNA on osteoclast activation,and the regulatory mechanism is mainly ceRNA mechanism.(5)In conclusion,an in-depth study of the regulatory mechanism of extracellular vesicles carrying non-coding RNA on osteoclast activation is helpful to find key targets for the treatment of skeletal system-related diseases.
6.Value of CT imaging radiomics in predicting the clinical efficacy of extracorporeal shock wave lithotripsy for pancreatic duct stones
Chunying WU ; Xiaofei JIAO ; Chunjie WANG ; Weigang GU ; Zhongxiang DING ; Xiaofeng ZHANG
Chinese Journal of Pancreatology 2024;24(4):287-292
Objective:To investigate the value of CT imaging radiomics in predicting the therapeutic effect of extracorporeal shock wave lithotripsy (ESWL) for pancreatic duct stones.Methods:The clinical data of 167 patients with pancreatic duct stones treated with ESWL in the Department of Gastroenterology, the First People's Hospital of Hangzhou, Westlake University from July 2016 to January 2023 were retrospectively analyzed. Patients were divided into complete lithotripsy group (stone diameter ≤3 mm, n=94) and incomplete lithotripsy group (stone diameter>3 mm, n=73), according to the size of the largest residual stone after the first ESWL treatment. ITK SNAP software was used to delineate the images of pancreatic duct stones, and the artificial intelligence tool kit developed by United Shadow Company was used to extract the image radiomics characteristics. The pancreatic duct stone data set was randomly assigned into the training set ( n=118) and the test set ( n=29) in the ratio of 8∶2, and the absolute maximum normalization treatment was used, followed by peacekeeping selection through the minimum absolute contraction and selection operator (Lasso) to calculate the CT image radiomics score, and the logistic regression classifier was used to construct the ESWL treatment effect prediction model of pancreatic duct stones. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) and sensitivity, specificity, and accuracy were calculated to assess the performance of the prediction model. Decision curve analysis was used to evaluate the clinical value of CT radiomics score in the diagnosis of ESWL for pancreatic duct stones. Results:A total of 2 287 imaging radiomics characteristics were extracted, and 11 optimal imaging radiomics characteristics were finally screened by Lasso regression dimensionality reduction to establish a prediction model for ESWL treatment effect of pancreatic duct stones. The AUC values of the training set and the test set were 0.89 and 0.87, respectively, and the sensitivity, specificity, and accuracy were 82% and 79%, 82% and 82%, 82% and 80%, respectively. The AUC value in the independent validation set was 0.90, and the sensitivity, specificity, and accuracy were 78%, 90%, and 85%, respectively. The results of decision curve analysis showed that when the probability of ESWL efficacy in the diagnosis of pancreatic duct stones with CT image radiomics score was >0.05, the use of CT image radiomics score in the diagnosis of ESWL efficacy in pancreatic duct stones was more beneficial to patients in clinical practice than not.Conclusions:The treatment effect of ESWL for pancreatic duct stones can be predicted by CT imaging radiomics model.
7.Initial clinical outcomes of the comprehensive debulking surgery for one-stage reconstruction of multiple toes macrodactyly in children
Guoqing CHEN ; Xiaofei TIAN ; Xionghui DING ; Jun XIAO ; Hai ZHU ; Ailian MEI ; Chao WEI
Chinese Journal of Plastic Surgery 2024;40(6):587-596
Objective:To evaluate the initial clinical outcome of applying a comprehensive debulking procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle to reconstruct the hypertrophic toes and forefoots in one-stage surgery in multiple toes macrodactyly in children.Methods:The clinical data of children with macrodactyly deformity treated by the Department of Burn and Plastic Surgery in Children’s Hospital of Chongqing Medical University from January 2022 to October 2023 were retrospectively analyzed. Design toe and plantar arbitrary flaps with a few vascular perforating branches which pedicle at the comparatively healthy proximal side and resect all tissues beyond the normal length. In severe toe, a composite tissue nail-flap with the artery was dissected to reconstruct the toenail. Fat debulking on the surface of deep plantar fascia as well as within the osseofascial sheath, resecting partially of the fatty infiltrated nerve, transverse and longitudinal osteotomy to shorten and narrowed phalanxes without epiphyseal block, arthroplasty and flexor tendon tightening were performed. Finally, toes shaped by wrapping toe flaps, and pelmas restored by plantar flaps which both with comparatively healthy proximal pedicle. The operation time, healing time, and whether the toes and toenails are preserved were all recorded. The maximum circumference of both foot, the difference in shoe size, the presence of skin ulcers, wound scars, toe webbing morphology, the presence of basic sensation, and the satisfaction of parents were followed-up after surgery. The modified follow-up questionnaire was used to evaluate the surgical effect, the total score is 0-12 points, and the higher the score, the better the surgical outcome. Descriptive methods was used for statistical analysis, and the measurement data conforming to normal distribution were expressed as Mean±SD.Results:A total of 15 patients were enrolled, including 11 males and 4 females. The median age at the time of operation was 2.75 years (0.9-10.8 years). There were 11 cases with 2 toes and 4 cases with 3 toes, a total of 34 toes involved. The average surgical duration was 4.13 hours (3.25 hours for 2 toes and 5.00 hours for 3 toes). Only one severe case with 3 toes involved was amputated the biggest toe ray and totally 2 toe nail flaps were harvested unsuccessfully intraoperative. Except 3 toes had distal skin partially necrosis and 2 nail flaps were completely necrotic which healed after dressing changes, the rest of the toes were healing well after operation. The average follow-up time was 4.8 months (3-11 months), the difference of circumference was less than 1.5 cm, as well as in length was less than 0.5 cm between feet and all children were able to wear the appropriate shoes with same size. A total of 4 toes failed to retain toenails, and 1 had a very thin toenail. Except for one case with insufficient web depth, the other toe webs were close to normal. There was no skin ulcer occurred, the basic sensation of the feet was present, and wound scars were inconspicuous. The score of the modified questionnaire was 10.54±0.88, all parents were satisfied with the results.Conclusion:Comprehensive procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle for debulking multiple toes macrodactyly in children could completely excise distal hypertrophic tissues in a single operation, and the size of the affected feet and toes can be greatly reduced to wearing shoes of the same size, and have a high success rate in preserving the toes, as well as nails. The reconstructed feet, toes and toe webbing have near-normal morphology, hidden scar, no ulcers after walked and achieve a good initial effect.
8.Correlations of pulmonary function and chronic lung diseases with headache in middle-aged and elderly people in China:based on CHARLS
Yu GUO ; Changli WANG ; Ren DING ; Wenbin LU ; Xiaofei LI
Academic Journal of Naval Medical University 2024;45(11):1395-1401
Objective To explore the relationships between headache and pulmonary function,chronic lung disease(CLD)in middle-aged and elderly people in China.Methods This cross-sectional study collected data from participants aged 45 and above in the 2015 China Health and Retirement Longitudinal Study(CHARLS).Headache was diagnosed based on self-report,and CLD and asthma were defined by self-reported doctor diagnoses or a combination of health assessments and medication use.Peak expiratory flow(PEF)was used as an indicator of pulmonary function.Multivariable logistic regression model was used to analyze the correlations between PEF,asthma,CLD,and headache.Relationship between PEF and headache was analyzed by restricted cubic spline(RCS)analysis and subgroup analysis.Results Among 12 661 middle-aged and elderly participants,the prevalence of headache was 14.42%(1 826/12 661),with a prevalence of 9.07%(558/6 151)in males and 19.48%(1 268/6 510)in females.After full adjustment for covariates,each 1 L/s increase in PEF was associated with a 7%reduction in the risk of headache(odds ratio[OR]=0.93,95%confidence interval[CI]0.90-0.96,P<0.001).Categorizing PEF into quartiles(Q1-Q4),as the increase of PEF,the risk of headache significantly decreased(ORs for Q2,Q3,and Q4 were 0.92,0.82,and 0.72,respectively,Ptrend<0.001).Additionally,asthma(OR=1.78,95%CI 1.43-2.20,P<0.001)and CLD(OR=2.21,95%CI 1.92-2.53,P<0.001)were positively associated with the risk of headache.RCS analysis indicated a negative linear correlation between PEF and the risk of headache(Poverall<0.001,Pnon-linear=0.57).Subgroup analysis revealed that a history of hypertension had a significant impact on the negative association between PEF and headache(Pinteraction<0.001).Conclusion There is a significant negative correlation between PEF and headache among middle-aged and elderly people in China,while asthma and CLD are positively associated with headache.Improving lung function in middle-aged and elderly populations may be an effective strategy for preventing or alleviating headache.
9.Mechanisms of ionizing radiation-induced pyroptosis in human intestinal epithelial cells
Qiong WANG ; Jian HONG ; Jin GUO ; Junzhao DUAN ; Kexin DING ; Fumin TAI ; Xiaofei ZHENG ; Changhui GE
Military Medical Sciences 2024;48(4):241-250
Objective To investigate the mechanism underlying gasdermin E(GSDME)-mediated pyroptosis in radiation-induced intestinal injury and to find out whether gasdermin(GSDM)family members regulate pyroptosis through similar signaling pathways.Methods Human normal colon epithelial cells(NCM460)and human colon cancer cells(HT-29)were exposed to radiation of different doses and durations before pyroptosis indicators were evaluated by observing pyroptotic bubbles,cell survival,and the cleavage of pyroptosis execution proteins.HT-29 cells overexpressing GSDME were subjected to radiation,followed by enrichment analysis of pyroptosis-related differentially expressed genes using RNA-seq.Results Radiation induced substantial pyroptosis in NCM460 cells.Overexpression of GSDME in HT-29 cells resulted in substantial radiation-induced pyroptosis.The pyroptosis state of human intestinal cells was simulated in the HT-29 model cell line.Overexpressions of GSDME-N and GSDMD-N resulted in the expression of more than 50% of the differentially expressed genes in the pyroptosis state.Sequencing analysis showed that the genes in the pyroptosis state were mainly overrepresented in immune response,inflammatory response,and Rapl signaling pathway.Conclusion GSDME activation can mediate radiation-induced pyroptosis by producing GSDME-N fragments.GSDM family members participate in pyroptosis in a similar mode of regulation.Furthermore,radiation-induced activation of GSDME/D may regulate pyroptosis through immune response,inflammatory response,and Rap1 signaling pathway.
10.Glutathione peroxidase 3-modified mesenchymal stem cells attenuate radiation-induced lung injury by reducing oxidative damage
Rui ZHAI ; Fumin TAI ; Kexin DING ; Changhui GE ; Xiaofei ZHENG ; Hanjiang FU
Military Medical Sciences 2024;48(7):487-494
Objective To investigate the protective effect and mechanism of glutathione peroxidase 3-(GPx3)modified mesenchymal stem cells(MSC)against radiation-induced lung injury(RILI).Methods GPx3-modified MSCs were injected into the tail vein of mice whose lungs were irradiated with 20 Gy.Lung tissues were collected and sections were stained to observe pathological changes.The expression levels of inflammation-related factors were detected by real time quantitative PCR(qPCR),while the levels of malondialdehyde(MDA),H2O2,and 8-hydroxyguanine(8-OHG)were detected via biochemical experiments.Additionally,RNA damage was assessed by reverse transcription blocking combining with double primer PCR.Results GPx3-modified MSCs significantly improved the pathological damage in post-radiation lung tissues and inhibited the fibrosis process and inflammatory response.GPx3-modified MSCs were able to scavenge reactive oxygen species(ROS)more effectively,resulting in a reduction of lipid peroxidation products such as MDA and oxidative damage to RNA formation of 8-OHG.Conclusion By decreasing ROS accumulation,GPx3-modified MSCs can potentially reduce oxidative damage and attenuate RILI.GPx3-modified MSCs can improve the therapeutic efficacy against RILI.

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