1.Fexolone inhibits neuronal ferroptosis through the Nrf2/HO-1/GPX4 pathway to alleviates sepsis-associated brain injury.
Rao SUN ; Jinyao ZHOU ; Yang JIAO ; Kaixuan NIU ; Cheng YUAN ; Ximing DENG
Chinese Critical Care Medicine 2025;37(5):452-457
OBJECTIVE:
To observe the protective effect of Fisetin on sepsis-associated brain injury and explore its possible mechanism from the perspective of ferroptosis.
METHODS:
Sprague-Dawley (SD) rats (6-8-week-old male) were randomly divided into three groups: sham operation group (Sham group), colonic ligation and puncture (CLP) induced sepsis model group (CLP group) and Fisetin preprocessing group (CLP+Fisetin group), with 18 rats in each group (12 for observing survival rate and 6 for indicator testing). The CLP+Fisetin group was given Fisetin solution 50 mg×kg-1×d-1 by gavage continuously for 5 days before CLP, with dimethyl sulfoxide (DMSO) as the solute, while Sham group and CLP group were given the same dose of DMSO. The model was established at 2 hours after the last gavage. The general condition of each group of rats were observed, and the 10-day mortality were record. The behavioral testing (new object recognition experiment, elevated cross maze experiment) were performed after 7 days of modeling. After 24 hours of modeling, nerve reflex scoring was performed, and then the rats were euthanized and brain tissue was collected. The pathological changes of brain tissue were observed under a microscope by hematoxylin-eosin (HE) staining, the deposition of iron ion in brain tissue was observed by Prussian blue staining. The content of iron in brain tissue was determined by tissue iron kit, and the content of malondialdehyde (MDA) in brain tissue was determined by colorimetry. The expressions of tumor necrosis factor-α (TNF-α), neuron damage marker S100β, nuclear factor E2-related factor 2 (Nrf2), heme oxygenases-1 (HO-1) and glutathione peroxidase 4 (GPX4) were detected by Western blotting.
RESULTS:
On day 10 post-operation, 12, 3, and 7 animals survived in the Sham group, CLP group, and CLP+Fisetin group, respectively. Compared with the Sham group, rats in the CLP group showed significantly decreased nerve reflex score, new object discrimination index and open arm dwell time. HE staining showed arranged disorderly of neuronal cells, cytoplasm deep staining, nuclear condensation, unclear structures, neuron loss, and significant inflammation in the hippocampus in the hippocampus. Prussian blue staining showed iron ion deposition in the brain tissue. The contents of iron and MDA in brain tissue were elevated, and the expressions of TNF-α and S100β were up-regulated, while the expressions of Nrf2, HO-1, and GPX4 were down-regulated. Compared with the CLP group, the CLP+Fisetin group showed significantly increased neurological reflex score (7.33±1.15 vs. 4.67±1.53), improved new object discrimination index (0.44±0.02 vs. 0.32±0.04), and longer open arm dwell time (minutes: 78.33±9.29 vs. 41.15±9.64). Neuronal cells in the hippocampus were more organized, with less cytoplasmic staining, nuclear condensation, reduced neuronal loss, and fewer inflammatory cells. Iron ion deposition was reduced, and the contents of iron ions and MDA in brain tissue were decreased [iron ion (μg/g): 151.27±14.90 vs. 224.69±17.64, MDA (μmol/g): 470.0±44.3 vs. 709.3±65.4]. The expressions of TNF-α and S100β were significantly decreased (TNF-α/GAPDH: 0.651±0.060 vs. 0.896±0.022, S100β/GAPDH: 0.685±0.032 vs. 0.902±0.014), while the expressions of Nrf2, HO-1, and GPX4 were significantly increased (Nrf2/GAPDH: 0.708±0.108 vs. 0.316±0.112, HO-1/GAPDH: 0.694±0.022 vs. 0.538±0.024, GPX4/GAPDH: 0.620±0.170 vs. 0.317±0.039). All differences were statistically significant (all P < 0.05).
CONCLUSION
Fisetin pretreatment can inhibit ferroptosis and reduce sepsis-associated brain injury by Nrf2/HO-1/GPX4 pathway.
Animals
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Ferroptosis/drug effects*
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Rats, Sprague-Dawley
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NF-E2-Related Factor 2/metabolism*
;
Sepsis/complications*
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Male
;
Rats
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Phospholipid Hydroperoxide Glutathione Peroxidase
;
Neurons/drug effects*
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Signal Transduction
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Brain Injuries/metabolism*
;
Flavonols
;
Flavonoids/pharmacology*
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Heme Oxygenase-1/metabolism*
;
Heme Oxygenase (Decyclizing)
2.Characteristics of transient remission of islet function and its influence on long-term prognosis in different onset age patients with type 1 diabetes mellitus
Xuemei SHE ; Peiwen TIAN ; Ximing SUN
Chinese Journal of Diabetes 2024;32(6):432-436
Objective To investigate the characteristics of transient remission of islet function and its influence on long-term prognosis in different onset age patients with type 1 diabetes mellitus(T1DM).Methods 156 newly diagnosed T1DM patients who received treatment and completed follow-up were retrospectively chosen from January 2014 to January 2018.All patients were grouped according to the onset age including childhood group(n=18),adolescent group(n=108),adult group(n=30).The transient remission and retention rate of islet function of three groups were compared.The relationship between onset age and c-peptide level was analyzed.Results BMI,FC-P,and 2 hC-P levels in adolescent group were higher than those in childhood group(P<0.05).The positivity rates of protein tyrosine phosphatase and zinc transporter 8 antibodies in adult group were lower than those in childhood group(P<0.05).The incidence of transient remission of pancreatic function in adolescent group was higher than that in childhood and adult groups(P<0.05).The duration of transient remission of pancreatic function in adolescent and adult groups was lower than that in childhood group(P<0.05).The islet function retention rates in adolescent group after 1 and 4 years from onset were higher than those in childhood and adult groups(P<0.05).Generalized estimation equation analysis showed that the long-term FC-P and 2 hC-P in adolescent group were higher than those in childhood and adult groups(P<0.05).The FC-P and 2 hC-P levels in adult patients with previous transient remission were higher than those in childhood group(P<0.05).Conclusions Adolescent onset T1DM patients are more likely to have transient remission of islet function,while childhood onset patients have longer transient remission of islet function.In addition,the adult T1DM patients had the best long-term islet function in transient remission population.
3.The imaging characteristics of primary intestinal lymphoma
Bing KANG ; Shuo ZHANG ; Ximing WANG ; Cong SUN
Chinese Journal of Radiology 2024;58(10):1075-1079
Objective:To summarize the imaging characteristics of primary intestinal lymphoma (PIL).Methods:As a cross-sectional study, a total of 103 consecutive patients diagnosed as PIL by pathology were retrospectively enrolled at Affiliated Shandong Provincial Hospital of Shandong First Medical University between January 2013 to December 2023. Ninety-four patients underwent CT plain and enhanced scans, and the remaining 9 patients only underwent MRI examination. Imaging features were evaluated, including the location and shape of the tumor, the shape of the intestinal wall and lumen, abdominal lymph nodes, the density or signal intensity of the tumor, and the degree and mode of enhancement after the enhancement scan.Results:The most frequent location of PIL was the ileum (43.7%, 45/103), followed by the ascending colon (20.4%, 21/103). Ninety-one patients had a single lesion (88.3%), while the other 12 patients had multiple lesions (11.7%). Diffuse large B-cell lymphoma was the most common histopathological type of the PIL (65.0%, 67/103), followed by mucosa-associated lymphoid tissue lymphoma (9.7%, 10/103). Generally, PIL classically presented intestinal wall thickening (81.6%, 84/103) and exophytic mass (28.2%, 29/103). Aneurysmal dilatation of the lumen appeared in 19 patients. Nineteen tumors (18.4%) grew out of the lumen, and perforation was shown in 3 patients. Bulky mesenteric or retroperitoneal adenopathy occurred in 28 patients (27.2%). Seventy-two tumors (69.9%) showed homogeneous enhancement, and 75 (72.8%) showed mild-to-moderate enhancement. In DWI images, all 9 tumors showed significant diffusion limitation.Conclusions:The most frequent location of PIL was the ileum. The main imaging characteristics were segmental intestinal wall thickening, which showed mild-to-moderate homogeneous enhancement and restricted diffusion.
4.Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly (version 2023)
Yan HU ; Dongliang WANG ; Xiao CHEN ; Zhongmin SHI ; Fengjin ZHOU ; Jianzheng ZHANG ; Yanxi CHEN ; Liehu CAO ; Sicheng WANG ; Jianfei WANG ; Hongliang WANG ; Yong FENG ; Zhimin YING ; Chengdong HU ; Qinglin HAN ; Ming LI ; Xiaotao CHEN ; Zhengrong GU ; Biaotong HUANG ; Liming XIONG ; Yunfei ZHANG ; Zhiwei WANG ; Baoqing YU ; Yong WANG ; Lei ZHANG ; Lei YANG ; Peijian TONG ; Ximing LIU ; Qiang ZHOU ; Feng NIU ; Weiguo YANG ; Wencai ZHANG ; Shijie CHEN ; Jinpeng JIA ; Qiang YANG ; Tao SHEN ; Bin YU ; Peng ZHANG ; Yong ZHANG ; Jun MIAO ; Kuo SUN ; Haodong LIN ; Yinxian YU ; Jinwu WANG ; Kun TAO ; Daqian WAN ; Lei WANG ; Xin MA ; Chengqing YI ; Hongjian LIU ; Kun ZHANG ; Guohui LIU ; Dianying ZHANG ; Zhiyong HOU ; Xisheng WENG ; Yingze ZHANG ; Jiacan SU
Chinese Journal of Trauma 2023;39(4):289-298
Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.
5.Development and validation of a CT-based radiomics model for differentiating pneumonia-like primary pulmonary lymphoma from infectious pneumonia: A multicenter study.
Xinxin YU ; Bing KANG ; Pei NIE ; Yan DENG ; Zixin LIU ; Ning MAO ; Yahui AN ; Jingxu XU ; Chencui HUANG ; Yong HUANG ; Yonggao ZHANG ; Yang HOU ; Longjiang ZHANG ; Zhanguo SUN ; Baosen ZHU ; Rongchao SHI ; Shuai ZHANG ; Cong SUN ; Ximing WANG
Chinese Medical Journal 2023;136(10):1188-1197
BACKGROUND:
Pneumonia-like primary pulmonary lymphoma (PPL) was commonly misdiagnosed as infectious pneumonia, leading to delayed treatment. The purpose of this study was to establish a computed tomography (CT)-based radiomics model to differentiate pneumonia-like PPL from infectious pneumonia.
METHODS:
In this retrospective study, 79 patients with pneumonia-like PPL and 176 patients with infectious pneumonia from 12 medical centers were enrolled. Patients from center 1 to center 7 were assigned to the training or validation cohort, and the remaining patients from other centers were used as the external test cohort. Radiomics features were extracted from CT images. A three-step procedure was applied for radiomics feature selection and radiomics signature building, including the inter- and intra-class correlation coefficients (ICCs), a one-way analysis of variance (ANOVA), and least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and construct a clinical factor model. Two radiologists reviewed the CT images for the external test set. Performance of the radiomics model, clinical factor model, and each radiologist were assessed by receiver operating characteristic, and area under the curve (AUC) was compared.
RESULTS:
A total of 144 patients (44 with pneumonia-like PPL and 100 infectious pneumonia) were in the training cohort, 38 patients (12 with pneumonia-like PPL and 26 infectious pneumonia) were in the validation cohort, and 73 patients (23 with pneumonia-like PPL and 50 infectious pneumonia) were in the external test cohort. Twenty-three radiomics features were selected to build the radiomics model, which yielded AUCs of 0.95 (95% confidence interval [CI]: 0.94-0.99), 0.93 (95% CI: 0.85-0.98), and 0.94 (95% CI: 0.87-0.99) in the training, validation, and external test cohort, respectively. The AUCs for the two readers and clinical factor model were 0.74 (95% CI: 0.63-0.83), 0.72 (95% CI: 0.62-0.82), and 0.73 (95% CI: 0.62-0.84) in the external test cohort, respectively. The radiomics model outperformed both the readers' interpretation and clinical factor model ( P <0.05).
CONCLUSIONS
The CT-based radiomics model may provide an effective and non-invasive tool to differentiate pneumonia-like PPL from infectious pneumonia, which might provide assistance for clinicians in tailoring precise therapy.
Humans
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Retrospective Studies
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Pneumonia/diagnostic imaging*
;
Analysis of Variance
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Tomography, X-Ray Computed
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Lymphoma/diagnostic imaging*
6.Preoperative ascending aorta diameter and prognosis analysis of patients with acute type A aortic dissection
Yuduo WU ; Ming GONG ; Lizhong SUN ; Lianjun HUANG ; Yongmin LIU ; Junming ZHU ; Tianxiang GU ; Ruixin FAN ; Ximing QIAN ; Yihua HE ; Hongjia ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(4):235-240
Objective:To investigate the preoperative ascending aorta diameter in patients with acute type A aortic dissection in the Chinese population, compares and analyze the differences in preoperative blood biomarkers, and evaluate the impact of the preoperative ascending aorta diameter in this part of patients on the short-term prognosis of patients.Methods:A collection of 641 patients with acute type A aortic dissection who were enrolled in the " Acute Aortic Syndrome High-Risk Early Warning and Intervention Study" project from January 2018 to January 2020 were collected. Divide the patients into two groups (group Ⅰ<55 mm, group Ⅱ≥55 mm) according to the preventive intervention value of ascending aorta diameter recommended by the guideline for studying preoperative ascending aorta diameter difference in blood biomarkers and the influence of ascending aorta diameter on the short-term prognosis of patients. All patients had CT scans to assess the diameter of the ascending aorta before operation.Results:In this study, all patients with acute type A aortic dissection had a mean preoperative ascending aorta diameter of (46.9±9.7)mm. The preoperative ascending aorta diameter of all patients was less than 55 mm, accounted for 84.1%. Male patients were more likely to have aortic dissection than females; most patients' age was less than 60 years old. The preoperative blood inflammatory index counts were higher in the ascending aorta diameter ≥55 mm group. However, the long-term prognosis of patients with different ascending aorta diameters before surgery was not apparent in this study. The preoperative survival rate and short-term survival rate of patients with ascending aorta diameter <55 mm were higher than those of other groups, but the difference was not statistically significant.Conclusion:In patients with acute type A aortic dissection, the diameter of the ascending aorta is usually less than 55 mm. Moreover, the blood inflammatory index counts are high in the preoperative ascending aorta diameter ≥55 mm group. Meanwhile, patients with smaller ascending aorta diameter have better survival rate and short-term prognosis.
7.Preoperative risk factors for the onset of acute Stanford type A aortic dissection in a multicenter study: A retrospective cohort study
Yuduo WU ; Ming GONG ; Lizhong SUN ; Lianjun HUANG ; Yongmin LIU ; Junming ZHU ; Tianxiang GU ; Ruixin FAN ; Ximing QIAN ; Hongjia ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(08):986-991
Objective To evaluate the preoperative risk factors for acute Stanford type A aortic dissection (ASTAAD) patients in our country by collecting multi-center data. Methods We consecutively enrolled 700 patients who underwent surgery for ASTAAD in the multi-center hospital database from January 2018 to January 2020. According to the ascending aorta size (AAS), the patients were divided into two groups: a group AAS≥55 mm and a group AAS< 55 mm. Univariate and multivariate logistic regression analyses were used to investigate the related preoperative risk factors for the onset of ASTAAD. Results According to the exclusion criteria, a total of 621 patients were finally enrolled, including 453 males and 168 females with an average age of 48.24±11.51 years, and 509 (81.94%) patients had AAS< 55 mm. Univariate and multivariate statistical analyses showed that smoking, hypertension, preoperative cardiac troponin I, and left ventricular ejection fraction were related to the occurrence of ASTAAD. The mortality rate of the patient during hospitalization was 13.04% (81 patients). Conclusion In clinical practice, various preoperative risk factors affect ASTAAD patients, which should be paid attention to. Comprehensive evaluation and an individualized analysis of patients and timely prevention and intervention improve patients' survival rate.
8.Comparisons of serum procalcitonin and fibrinogen degradation product levels between type 2 diabetes mellitus patients with Escherichia coli bloodstream and urinary tract infections
Huiqing WANG ; Jinhua ZHANG ; Yinyu LI ; Jimin ZHANG ; Zhengli HUANG ; Ximing SUN ; Shaoqing XUE ; Jiezhong YU
Chinese Journal of Primary Medicine and Pharmacy 2021;28(12):1761-1766
Objective:To compare serum procalcitonin and fibrinogen degradation product levels between type 2 diabetes mellitus patients with Escherichia coli bloodstream and urinary tract infections. Methods:The clinical data of 82 type 2 diabetes mellitus patients with Escherichia coli infections who received treatment between December 2014 and December 2019 in the First Affiliated Hospital of Datong University (The Fifth People's Hospital of Datong) were retrospectively analyzed. These patients were assigned to bloodstream infection ( n = 40) and urinary tract infection ( n = 42) according to the way of Escherichia coli infection. Serum procalcitonin and fibrinogen degradation product levels, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein, white blood cell count, D-Dimer level, antithrombin III activity, and electrolytes were determined and compared between the two groups. Correlation between procalcitonin and other variables was analyzed. Multiple linear regression analysis was performed with procalcitonin level as a dependent variable and other relevant indexes as independent variables. Results:Body temperature, white blood cell count, neutrophil count, monocyte count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, procalcitonin level, C-reactive protein level, fibrinogen degradation product level, and D-Dimer level in the bloodstream injection group were (39.49 ± 0.64) ℃, (14.92 ± 11.78) × 10 9/L, (13.39 ± 11.60) × 10 9/L, (0.72 ± 0.36) ×10 9/L, (14.86 ± 10.52), (199.15 ± 160.69), (22.81 ± 17.86) μg/L, (133.44 ± 63.63) mg/L, (49.71 ± 41.44) mg/L, (16.56 ± 12.20) mg/L, respectively, which were significantly higher than those in the urinary tract infection group [(37.12 ± 1.20) ℃, (9.04 ± 3.95) × 10 9/L, (6.25 ± 4.02) × 10 9/L, (0.42 ± 0.29) × 10 9/L, (3.67 ± 3.34), (120.01 ± 44.08), (4.46 ± 8.69) μg/L, (39.22 ± 22.16) mg/L, (3.81 ± 3.41) mg/L, (0.84 ± 0.75) mg/L), t = 7.356, 2.578, 3.162, 2.958, 5.538, 2.591, 2.810, 4.825, 2.902, 2.375, all P < 0.05]. Platelet count, lymphocyte count, blood sodium level and antithrombin Ⅲ activity in the bloodstream infection group were (167.50 ± 104.93) × 10 9/L, (1.06 ± 0.58) × 10 9/L, (130.89 ± 6.50) mmol/L, (57.88 ± 16.28)% , which were significantly lower than those in the urinary tract infection group [(239.40 ± 82.52)× 10 9/L, (2.14 ± 0.71) × 10 9/L, (138.46 ± 5.96) mmol/L, (90.11 ± 8.90)%, t = -2.853, -6.313, -4.046, -7.350, all P < 0.05]. Correlation analysis revealed that serum procalcitonin level was positively correlated with body temperature ( r = 0.387), white blood cell count ( r = 0.355), neutrophil count ( r = 0.368), C-reactive protein ( r = 0.605), fibrinogen degradation product level ( r = 0.616), D-Dimer level ( r = 0.486) (all P < 0.05), and it was negatively correlated with sodium level ( r = -0.319) and antithrombin Ⅲ activity ( r = -0.465) (both P < 0.05). Multiple linear regression analysis results revealed that fibrinogen degradation product level and body temperature were greatly correlated with procalcitonin level. Conclusion:Inflammatory indicators procalcitonin level, body temperature, white blood cell count, neutrophil count, C-reactive protein, fibrinogen degradation product level and D-Dimer level were remarkably higher in type 2 diabetes mellitus patients with Escherichia coli bloodstream infection than those in type 2 diabetes mellitus patients with Escherichia coli urinary tract infection. Procalcitonin level was greatly correlated with body temperature and fibrinogen degradation product level.
9.Psychological first aid during severe nuclear power plant accident
Huifang CHEN ; Quanfu SUN ; Long YUAN ; Ximing FU ; Cuiping LEI
Chinese Journal of Radiological Health 2021;30(1):48-52
The past three severe nuclear power plant accidents showed that the social psychological impact on the public is the most serious consequence of severe nuclear power plant accidents. When a severe nuclear power plant accident occurs, individuals / groups in the affected area may experience various stress reactions. Timely and effective psychological first-aid can help the victims to survive the crisis effectively and actively respond to the current life. Referring to the World Health Organization guide psychological first aid: guide for field workerand other national guidance, this paper introduces how emergency rescue personnel carry out emergency psychological assistance in case of severe nuclear accident.
10.Effect of different combination of locking compression plate's holes and screw on the axial micromotion of fracture site
Zaijie SUN ; Siyu YANG ; Guodong WANG ; Xianhua CAI ; Ximing LIU
Chinese Journal of Trauma 2020;36(4):341-346
Objective:To investigate the effect of different screw and screw hole combination of locking compression plates (LCP) on axial micromotion of fracture ends.Methods:Eighteen mature male New Zealand white rabbits were enrollled and divided into Groups A, B and C according to the random number table method, with six rabbits in each group. After obtaining the whole fresh right tibial specimens, the tibia was cut off transversely at the middle part and fixed with LCP. All specimens were fixed with locking screws in locking holes at the distal side of the fracture end. In Group A, locking screws were fixed in locking holes at proximal end. In Group B, common screws were fixed in locking holes at proximal end. While in Group C, common screws were fixed in compression holes at proximal end. All specimens were subjected to a dynamic axial load of 0-50 N on a universal test machine. The distance of the micromotion of the fracture site was measured and axial compression stiffness corresponding to each fixing method was calculated through the instrument's own system.Results:All specimens generated corresponding axial displacement under the axial load. Under an axial load that approximated a body weight (25 N), the axial displacement value of the fracture end was (0.101±0.017)mm in Group A, (0.164±0.007)mm in Group B, and (0.305±0.041)mm in Group C. Under the axial load of approximately two body weights (50 N), the axial displacement value of the fracture end was (0.218±0.012)mm in Group A, (0.285±0.013)mm in Group B, and (0.513±0.051)mm in Group C. Under the same load, the average axial displacement value of fracture site was Group C>Group B>Group A ( P<0.01). The axial stiffness of LCP device was (234.36±13.28)N/mm in Group A, (203.78±16.46)N/mm in Group B, and (112.62±16.23)N/mm in Group C, namely Group A>Group B>Group C ( P<0.01). Conclusion:LCP fixed with common screws or via compression holes can significantly increase axial micromotion of the fracture end. While the combined application of the two methods has better effect and can reduce the stiffness of LCP device.

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