1.Effect of wogonin on nerve injury in rats with diabetic cerebral infarction
Huanhuan WANG ; Panpan LIANG ; Jinshui YANG ; Shuxian JIA ; Jiajia ZHAO ; Yuanyuan CHEN ; Qian XUE ; Aixia SONG
Chinese Journal of Tissue Engineering Research 2025;29(11):2327-2333
BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.
2.HMGB1 gene knockout alleviates acute lung injury of sepsis mice via inhibiting TLR4/NF-κB pathway
Zhibin ZHANG ; Ruitong LI ; Weiwei ZHENG ; Xuerong LIN ; Ningning NIU ; Hui WANG ; Meng YUAN ; Shuchi HAN ; Qianlong XUE
Acta Universitatis Medicinalis Anhui 2024;59(2):248-253
Objective To study the effect of high mobility group box B1(HMGB1)gene knockout on alleviating a-cute lung injury and inhibiting toll-like receptor 4(TLR4)/nuclear factor-KB(NF-κB)pathway of sepsis mice.Methods Wild-type(WT)mice were divided into WT-Sham group and WT-model group,and HMGB1 knockout(KO)mice were divided into KO-sham group and KO-model group.Sepsis ALI model was established by cecal ligation and perforation in WT-model group and KO-model group.Sham operation was performed in WT-Sham group and KO-Sham group.24 h after modeling,the partial pressure of arterial oxygen(PaO2)was detected,oxy-genation index(OI)was calculated,pathological changes of lung tissue were detected and lung injury score was calculated,the concentrations of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),interleukin-6(IL-6),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),in serum and lung tissues and the expression of HMGB1,TLR4 and nuclear NF-κB in lung tissues were detected.Results The PaO2,OI and the concentration of SOD in serum and lung tissue of WT-model group were lower than those of WT-Sham group,the lung injury scores,the concentrations of TNF-α,IL-1 β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of HMGB1,TLR4 and nuclear NF-κB in lung tissue were higher than those in WT-Sham group(P<0.05).HMGB1 was not expressed in lung tissue of KO-model group,and the concentrations of PaO2,OI and the concentration of SOD in serum and lung tissue of KO-model group were higher than those of WT-model group,the lung injury scores,the concentrations of TNF-α,IL-1β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of TLR4 and nuclear NF-κB in lung tissue were lower than those of the WT-model group(P<0.05).Conclusion HMGB1 gene knockout alleviates acute lung injury of sepsis mice,the re-lated molecular mechanism may be the inhibition of TLR4/NF-κB pathway mediated inflammation and oxidative stress.
3.Overexpression of NRF1 alleviates mitochondrial and cognitive dysfunction in mice models of Alzheimer's disease
Lining SU ; Yanbing WANG ; Yongcai ZHANG
Acta Universitatis Medicinalis Anhui 2024;59(2):304-309
Objective To investigate the effects of nuclear respiratory factor 1(NRF1)on mitochondrial and cog-nitive dysfunction in Alzheimer's disease(AD)model mice.Methods The 5 × FAD mice were utilized as a mod-el for Alzheimer's disease,and the sparsely labeled AAV virus overexpressing NRF1(AAV-NRF1)was adminis-tered via stereotaxic injection into the brain.The expression of NRF1 in hippocampus was determined by Western blot,the morphology of mitochondria in hippocampus was observed by transmission electron microscope,the den-dritic spines of sparsely labeled neurons in the CA1 region were visualized and quantified using confocal laser mi-croscopy,cognitive and memory functions of mice were evaluated using the Morris water maze test,while electro-physiological methods were employed to detect long-term potentiation(LTP)of synaptic efficacy.Results The ex-pression of NRF1 in the hippocampus was significantly upregulated following stereotactic injection of AAV-NRF1(P<0.001).This intervention led to notable improvements in mitochondrial morphology within hippocampal neurons,as well as enhanced cognitive and memory functions in mice(P<0.01).Moreover,there was a significant in-crease in dendritic spine density among neurons located in the CA1 region of the hippocampus(P<0.001),ac-companied by long-lasting and stable long-term potentiation(LTP)and a substantial elevation in fEPSP slope(P<0.01).Conclusion The overexpression of NRF1 in a 5 × FAD mouse model of Alzheimer's disease(AD)initia-ted the restoration of mitochondrial dysfunction and enhanced synaptic plasticity,indicating that these alterations may contribute to the therapeutic efficacy of NRF1 overexpression in ameliorating cognitive dysfunction associated with AD.
4.Aortic stenosis of fetus caused by chimeric Y-chromosome isobaric double-adherent granules:A case report and literature review
Yulu QUAN ; Pingping ZHANG ; Yan LUO ; Jing HUO ; Xiaoping YU ; Yanmei SUN ; Yali LI
Journal of Jilin University(Medicine Edition) 2024;50(1):260-264
Objective:To confirm the potential etiological factors of congenital aortic stenosis(AS)by genetic analysis on prenatal diagnostic results of the fetus with AS.Methods:Amniocentesis for chromosomal G-band karyotyping combinated with single nucleotide polymorphism array(SNP-array)analysis was conducted on the amniotic fluid collected from a 25-week pregnant woman diagnosed as"fetus AS";chromosome karyotyping was also performed on the peripheral blood of the fetal parents.Results:The fetal karyotype analysis showed a chimeric Y-chromosome isobaric double-adherent granules.The SNP-array analysis results revealed a 11.2 Mb duplication in the Yp11.31q11.21 region and a 14.8 Mb deletion in the Yq11.21q11.23 region.Both the parents presented a normal karyotype,suggesting it was a newfound mutation.After extensive genetic counseling,the pregnant woman and her family chose to terminate the pregnancy locally.Conclusion:The chromosomal karyotype of the chimeric Y-chromosome isobaric double-adherent granules may be a contributing factor to the AS phenotype in the male fetus.The combined use of chromosomal karyotyping and SNP-array analysis on the amniotic cells is instrumental in the early diagnosis of the disease.
5.Correlation between lncRNA GAS5 and LHPP expression and epithelial-mesenchymal transformation in non-small cell lung cancer tissues and clinical significance
Liping CHEN ; Qiang JI ; Yanhong CHEN ; Yongxing SHI ; Ping FENG ; Weijia LIN ; Baoli XIANG ; Jianqing ZHAO
International Journal of Laboratory Medicine 2024;45(3):301-307,313
Objective To investigate the correlation between the expression of long non-coding ribonucleic acid growth arrest specific 5(lncRNA GAS5),phospholysine phosphohistidine inorganic pyrophosphate phos-phatase(LHPP)and epithelial-mesenchymal transition(EMT)in cancer tissues of patients with non-small cell lung cancer(NSCLC)and its clinical significance.Methods Cancer tissues and adjacent tissues of 90 patients with NSCLC who underwent surgical resection in the First Hospital Affiliated to Hebei North College from June 2018 to January 2020 were collected.The expressions of lncRNA GAS5,LHPP and EMT-associated pro-teins[E-calmodulin(E-Cad),N-calmodulin(N-Cad),and vimentin(VIM)]were detected by real-time fluores-cence quantitative polymerase chain reaction.The relationship between lncRNA GAS5 and LHPP mRNA and clinicopathological features in cancer tissues of NSCLC patients was analyzed,and the correlation between ln-cRNA GAS5 and LHPP mRNA and EMT-associated proteins expression in cancer tissues of NSCLC patients was analyzed by Pearson correlation.Kaplan-Meier method was used to plot the survival curves of NSCLC pa-tients with different lncRNA GAS5 and LHPP mRNA expressions,and multivariate Cox regression was used to analyze the prognostic factors of NSCLC patients.Results The expressions of lncRNA GAS5,LHPP mR-NA and E-Cad mRNA in cancer tissues of NSCLC patients were lower than those in adjacent tissues,while the expressions of N-Cad mRNA and VIM mRNA were higher than those in adjacent tissues,with statistical sig-nificance(P<0.05).Pearson correlation analysis showed that lncRNA GAS5 in cancer tissues of NSCLC pa-tients was positively correlated with E-Cad mRNA expression(r=0.724,P<0.001),and negatively correla-ted with N-Cad mRNA and VIM mRNA expression(r=-0.699,-0.689).P<0.001);lncRNA GAS5 was positively correlated with LHPP mRNA expression(r=0.651,P<0.001).The mRNA expressions of ln-cRNA GAS5 and LHPP in cancer tissues of NSCLC patients with different degrees of differentiation,tumor TNM stage and lymph node metastasis were significantly different(P<0.05).Kaplan-Meier survival curve a-nalysis showed that the 3-year overall survival rate in the lncRNA GAS5 high expression group[68.18%(30/44)]was higher than that in the lncRNA GAS5 low expression group[36.96%(17/46)].The 3-year overall survival rate in the high LHPP mRNA expression group[67.39%(31/46)]was higher than that in the lowLHPP mRNA expression group[36.36%(16/44)],and the difference was statistically significant(x2=10.274,10.322,P<0.05).Low differentiation,TNM stage Ⅲ and lymph node metastasis were independent risk factors for death in NSCLC patients,and lncRNA GAS5≥1.32 and LHPP mRNA≥1.12 were independ-ent protective factors(P<0.05).Conclusion The low expression of lncRNA GAS5 and LHPP mRNA in cancer tissues of patients with NSCLC is related to EMT-associated proteins expression,differentiation de-gree,tumor TNM stage,lymph node metastasis and prognosis,and may become a new target for the diagnosis and treatment of NSCLC.
6.Lipoprotein-associated phospholipase A 2 and cognitive impairment in patients with cerebral small vessel disease
Sai YAO ; Congcong YAN ; Xue BAI ; Wei JIN
International Journal of Cerebrovascular Diseases 2024;32(1):45-49
In recent years, the incidence of cerebral small vessel disease (CSVD) has been increasing with the aging of the population, and the cognitive impairment caused by it has brought huge burden to patients and their families. As a novel inflammatory biomarker, lipoprotein-associated phospholipase A 2 (Lp-PLA 2) directly participates in the pathogenesis of cognitive impairment in patients with CSVD by regulating circulatory vascular injury and neuroinflammation, and is expected to become a predictive indicator and therapeutic target for CSVD.
7.Application and evaluation study of 3D ultrasound in image guided radiotherapy for prostate cancer
Xin ZHAO ; Xuewu FAN ; Long TIAN ; Yimin HU
Journal of International Oncology 2024;51(1):43-49
Objective:To evaluate the accuracy of 3D ultrasound calibration in image guided radiotherapy for prostate cancer by taking cone beam CT calibration as the gold standard, and to analyze the risk factors of accuracy.Methods:From December 2018 to December 2021, 51 patients with prostate cancer from the Department of Radiation Oncology, First Affiliated Hospital of Hebei North University were selected as the study subjects. They received cone beam CT calibration based on bone and 3D ultrasound calibration based on soft tissue before fraction volumetric modulated arc therapy treatment three times a week. Taking cone beam CT calibration data as the gold standard, the Bland-Altman method was used to analyze the consistency of 3D ultrasound calibration data with the former. Taking 3 mm as the allowable threshold of accuracy, the calibration accuracy of 3D ultrasound relative to cone beam CT was evaluated. Logistic regression was used to analyze the risk factors affecting the accuracy of 3D ultrasound calibration.Results:A total of 765 pairs of cone beam CT and 3D ultrasound calibration data were obtained from 51 patients in left-right, superior-inferior and anterior-posterior directions. The calibration data of 3D ultrasound and cone beam CT were (1.39±0.11) and (1.13±0.07) mm in the left-right direction, (1.98±0.20) and (1.61±0.12) mm in the superior-inferior direction, (2.68±0.48) and (1.78±0.27) mm in the anterior-posterior direction, respectively, with statistically significant differences ( t=-6.42, P<0.001; t=-7.07, P<0.001; t=-7.34, P<0.001). The analysis results of Bland-Altman showed that the consistency of calibration data of the two methods were acceptable in three directions. The number of pairs of 3D ultrasound relative to cone beam CT calibration data difference <3 mm in the three directions were 676 (88.37%) on the left-right direction, 604 (78.95%) on the superior-inferior direction, and 577 (75.42%) on the anterior-posterior direction. The factors with statistically significant differences in the left-right direction included age ( χ2=18.27, P<0.001), prostate volume ( χ2=14.55, P<0.001), Charlson comorbidity index (CCI) ( χ2=8.01, P=0.005) and field range ( χ2=11.30, P<0.001). Age ( OR=2.02, 95% CI: 1.90-3.39, P=0.010) and the field range ( OR=1.45, 95% CI: 1.18-2.55, P=0.020) were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the left-right direction. The factors with statistically significant differences in the superior-inferior direction included age ( χ2=80.68, P<0.001), body mass index ( χ2=35.89, P<0.001) and field range ( χ2=40.39, P<0.001). Age ( OR=1.49, 95% CI: 1.15-2.09, P=0.021) and the field range ( OR=1.10, 95% CI: 1.01-1.90, P=0.034) were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the superior-inferior direction. The factors with statistically significant differences in the anterior-posterior direction included age ( χ2=46.07, P<0.001), CCI ( χ2=47.97, P<0.001) and field range ( χ2=11.86, P=0.001). Age ( OR=1.91, 95% CI: 1.22-3.45, P=0.015) and the field range ( OR=2.89, 95% CI: 1.45-3.90, P=0.001) were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the anterior-posterior direction. Conclusion:The consistency and accuracy of the calibration results of 3D ultrasound relative to cone beam CT are acceptable. It is necessary to consider the patient's age and field range to reduce the impact on accuracy before conducting 3D ultrasound calibration.
8.Therapeutic efficacy and mechanism of dandelion extract on intracerebral hemorrhage rats
Xiufeng ZHANG ; Xiaofei LI ; Jinghui WANG ; Huijing WANG ; Liwen WANG ; Cheng ZHEN ; Pengfei WANG ; Xipeng LIU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(2):212-216
Objective To investigate the therapeutic efficacy of dandelion extract on intracerebral hemorrhage(ICH)rats and its effect on nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods Stereotaxic intracranial injection of type Ⅳ col-lagenase was used to establish rat ICH model.Then 48 ICH rats were randomly divided into mod-el group,dandelion extract group,Nrf2 inhibitor(ML385)group and dandelion extract+ML385 group,with 12 rats in each group.Another 12 rats served as sham operation group.After treat-ment,neurological deficits was evaluated and scored for all groups of rats.Blood-brain barrier(BBB)function,neuronal apoptotic rate in the hippocampus,serum levels of COX-2,IL-6 and iNOS,cerebral contents of CAT,GSH-Px,ROS and MAD,and protein levels of Nrf2/HO-1 signal pathway were detected.Results Compared with sham operation group,the neurological deficit score,Evans blue exudation,appptotic rate of hippocampal neurons,serum COX-2,IL-6,iNOS levels,brain tissue reactive oxygen species(ROS)and malondialdehyde level in the model group were significantly increased(P<0.05),and the expression levels of CAT,GSH-Px,Nrf2 and HO-1 proteins were significantly decreased(P<0.05).Compared with dandelion extract group,combination of dandelion extract and ML385 significantly increased the neurological deficit score(2.54±0.23 vs 1.43±0.19),Evans blue exudation[(22.15±3.61)ng/mg vs(6.54±1.24)ng/mg],apoptotic rate[(31.97±5.26)%vs(3.51±0.94)%],serum COX-2[(5.82±1.16)ng/ml vs(1.34±0.42)ng/ml],IL-6[(1.47±0.31)ng/ml vs(0.43±0.14)ng/ml]and iNOS levels[(59.91±10.36)U/ml vs(13.94±3.78)U/ml],brain tissue ROS[(4.70±0.45)U/kg vs(1.70± 0.51)U/kg]and MDA levels[(3.72±0.52)nmol/mg vs(1.17±0.34)nmol/mg],and decreased expression levels of CAT[(2.54±0.59)U/mg vs(5.68±1.04)U/mg],GSH-Px[(8.01±0.86)U/mg vs(16.97±3.03)U/mg],Nrf2(0.67±0.13 vs 1.07±0.19)and HO-1(0.55±0.07 vs 0.86± 0.10,P<0.05).Conclusion Dandelion extract can enhance the antioxidant activity in ICH rats by activating Nrf2/HO-1 signaling pathway,prevent the progression of inflammation and oxida-tive stress,inhibit neuronal apoptosis in hippocampus,repair blood-brain barrier function,and thus improve nerve function.
9.Effect and mechanism of arctigenin on ventricular remodeling and inflammatory reaction in rats with chronic heart failure
Tingting ZHANG ; Yali MI ; Weina WANG ; Xiaoxia ZUO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(3):317-321
Objective To investigate the influences of arctigenin(ATG)on ventricular remodeling and inflammatory reaction in chronic heart failure(CHF)rats,and to analyze its potential mecha-nism.Methods A total of 79 SD rats were randomly divided into sham operation group(n=12),and the remaining rats were inflicted with abdominal aortic coarctation to establish a rat CHF model.After modeling,60 CHF rats were randomly divided into CHF group,low and high dose ATG group(ATG-L and ATG-H groups,10 and 20 mg/kg,respectively),ATG+NC group[20 mg/kg ATG+100 μl high mobility group protein B1(HMGB1)negative control plasmid],and ATG+HMGB1 group(20 mg/kg ATG+100 pl HMGB1 overexpression plasmid),with 12 rats per group.After 4 weeks of corresponding intervention,heart function,levels of B-type brain na-triuretic peptide(BNP),N-terminal B-type brain natriuretic peptide precursor(NT-proBNP)andIL-6 and TNF-α,heart mass index(HMI)and left ventricular mass index(LVMI),pathological changes of myocardial tissue,cross-sectional area of myocardial cells and myocardial collagen vol-ume fraction(CVF)and protein expression of HMGB1/Toll-like receptor 4(TLR4)/NF-κB sig-naling pathway in left ventricular myocardial tissue were measured.Results Compared with the sham operation group,myocardial tissue HMGB1(0.42±0.05 vs 0.15±0.02)and TLR4(0.70± 0.09 vs 0.21±0.04)protein levels,and phosphorylated NF-κB p65(p-NF-κB p65)/NF-κB p65(0.73±0.09 vs 0.26±0.05)protein ratio were obviously increased in the CHF group,while the left ventricular ejection fraction(LVEF)and left ventricular short-axis fractional shortening(LVFS)were obviously decreased(P<0.05).Myocardial tissue HMGB1(0.33±0.04、0.24±0.04 vs 0.42±0.05)and TLR4(0.56±0.06、0.41±0.05 vs 0.70±0.09)protein levels,and p-NF κB p65/NF-KB p65(0.61±0.08、0.49±0.06 vs 0.73±0.09)protein ratio were decreased,and the LVEF and LVFS were increased in the ATG-L group and ATG-H group than the CHF group(P<0.05).Overexpression of HMGB1 obviously attenuated the inhibitory effects of ATG on HMGB1/TLR4/NF-κB signaling pathway,ventricular remodeling,and inflammatory reaction in CHF rats(P<0.05).Conclusion ATG may suppress ventricular remodeling in CHF rats by in-hibiting HMGB1/TLR4/NF-κB signaling inflammatory pathway.
10.Modified Palmer classification of traumatic triangular fibrocartilage complex injury based on MRI
Canhua GAO ; Guoshi LÜ ; Zhijun HAO ; Yadong KANG ; Yanxia HAO ; Lei ZHENG
Journal of Practical Radiology 2024;40(1):88-91
Objective To classify traumatic triangular fibrocartilage complex(TFCC)injury based on 3.0T MR.Methods A total of 46 patients with definite history of wrist trauma admitted were collected.All patients underwent MRI scanning within 3 days after trauma,and the MRI findings were classified as follows according to the Palmer classification criteria:the focal structures of triangular fibro-cartilage(articular disc)(TFC)injury,the horizontal of the articular disc tear,injuries of ulnar styloid attachment and ulnar fovea attach-ment in TFC,ulnolunate and ulnotriquetral ligaments injuries,injury of the radial sigmoid notch junction,meniscal homologous inju-ry.The presence of TFCC injury was eventually confirmed by surgery in all patients.Results Of 46 patients,38 patients could be classified by Palmer,and there were 10 cases with type ⅠA,23 cases with type ⅠB,3 cases with type ⅠC and 2 cases with type ⅠD.A total of 8 patients were not suitable for Palmer type,and there were 3 patients with horizontal tears in the articular disc and 5 patients with meniscus homologous injuries.Conclusion The 3.0T MR can not only show various subtypes of Palmer classification,but also refine and supplement the classification based on the original classification,such as the injuries of ulnar styloid attachment and ulnar fovea attachment at the ulnar end of the articular disc,horizontal tear of the articular disc,meniscus homologous injury,etc.

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