1.Protective effect of Shenfu injection against neonatal hypoxic-ischemic brain injury by inhibiting the ferroptosis
Xiaotong Zhang ; Meng Zhang ; Gang Li ; Yang Hu ; Yajing Xun ; Hui Ding ; Donglin Shen ; Ming Wu
Acta Universitatis Medicinalis Anhui 2025;60(1):31-40
Objective :
To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis.
Methods :
An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression.
Results :
Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01).
Conclusion
Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.
2.An experimental study of a novel external fixator based on universal joints for the rapid initial stabilization of mandibular comminuted fractures
Zhi-Qiang HU ; Tai-Qiang DAI ; Lu ZHAO ; Xun LI ; Xu GONG ; Hao JIA ; Hai-Tao KONG ; Bo-Lei CAI ; Shi-Ping CHANG ; Lei TIAN
Chinese Journal of Traumatology 2024;27(5):254-262
Purpose::Shaping and assembling contemporary external fixators rapidly for the severe mandibular fractures remains a challenge, especially in emergency circumstance. We designed a novel external fixator that incorporates universal joints to provide the stabilization for mandibular comminuted fractures. This study aims to confirm the efficacy of this novel external fixator through biomechanical tests in vitro and animal experiments. Methods::In vitro biomechanical tests were conducted using 6 fresh canine with mandibular defect to simulate critical comminuted fractures. Three mandibles were stabilized by the novel external fixator and other mandibles were fixed by 2.5 mm reconstruction plates. All fixed mandibles were subjected to loads of 350 N on the anterior regions of teeth and 550 N on the first molar of the unaffected side. The stability was evaluated based on the maximum displacement and the slope of the load-displacement curve. In animal experiments, 9 beagles with comminuted mandibular fractures were divided into 3 groups, which were treated with the novel external fixation, reconstruction plate, and dental arch bar, respectively. The general observation, the changes in animals’ weight, and the surgical duration were recorded and compared among 3 groups. The CT scans were performed at various intervals of 0 day (immediately after the surgery), 3 days, 7 days, 14 days, 21 days, and 28 days to analyze the displacement of feature points on the canine mandible and situation of fracture healing at 28 days. The statistical significance was assessed by the two-way analysis of variance test followed by the Bonferroni test, enabling multiple comparisons for all tests using GraphPad Prism10.1.0 (GraphPad Inc, USA). Results::The outcomes of the biomechanical tests indicated that no statistically significant differences were found in terms of the maximum displacement ( p = 0.496, 0.079) and the slope of load displacement curves ( p = 0.374, 0.349) under 2 load modes between the external and internal fixation groups. The animal experiment data showed that there were minor displacements of feature points between the external and internal fixation groups without statistic difference, while the arch bar group demonstrated inferior stability. The CT analysis revealed that the best fracture healing happened in the internal fixation group, followed by the external fixation and arch baring at 28 days after fixation. The external fixation group had the shortest fixation duration (25.67 ± 3.79) min compared to internal fixation ((70.67 ± 4.51) min, p < 0.001) and arch baring ((42.00 ± 3.00) min, p = 0.046). Conclusion::The conclusion of this study highlighted the efficacy and reliability of this novel external fixator in managing mandibular fractures rapidly, offering a viable option for the initial stabilization of comminuted mandibular fractures in the setting of emergency rescue.
3.Research on Construction of Test Environment for Assessment of RF-Induced Heating Effects of Implants
Yonghua LI ; Lingfeng LU ; Jing WANG ; Chengling LI ; Pengfei YANG ; Zhichao WANG ; Dajing WU ; Xun LIU ; Sheng HU
Chinese Journal of Medical Instrumentation 2024;48(3):281-284,297
In magnetic resonance examination,the interaction between implants and the radio frequency(RF)fields induces heating in human tissue and may cause tissue damage.To assess the RF-induced heating of implants,three steps should be executed,including electromagnetic model construction,electromagnetic model validation,and virtual human body simulations.The crucial step of assessing RF-induced heating involves the construction of a test environment for electromagnetic model validation.In this study,a hardware environment,comprised of a RF generation system,electromagnetic field measurement system,and a robotic arm positioning system,was established.Furthermore,an automated control software environment was developed using a Python-based software development platform to enable the creation of a high-precision automated integrated test environment.The results indicate that the electric field generated in this test environment aligns well with the simulated electric field,making it suitable for assessing the RF-induced heating effects of implants.
4.Discussion on Magnetic Resonance Compatibility of Implantable Brain-Computer Interface Devices
Kaixiang JIN ; Xun LIU ; Sheng HU ; Yonghua LI ; Yuetong WU ; Jiaxing LI ; Chenghuai MO
Chinese Journal of Medical Instrumentation 2024;48(5):486-492
Brain-computer interface(BCI)devices are crucial tools for neural stimulation and recording,offering broad prospects in the diagnosis and treatment of neurological disorders.Furthermore,magnetic resonance imaging(MRI)is an effective and non-invasive technique for capturing whole-brain signals,providing detailed information on brain structures and activation patterns.Integrating the neural stimulation/recording capabilities of BCI devices with the non-invasive detection function of MRI is considered highly significant for brain function analysis.However,this combination imposes specific requirements on the magnetic and electronic performance of neural interface devices.The interaction between BCI devices and MRI is initially explored.Subsequently,potential safety risks arising from their combination are summarized and organized.Starting from the source of these hazards,such as the metallic electrodes and wires of BCI devices,the issues are analyzed,and current research countermeasures are summarized.In conclusion,the regulatory oversight of BCI's magnetic resonance safety is briefly discussed,and suggestions for enhancing the magnetic resonance compatibility of related BCI devices are proposed.
5.Exploration on the learning curve of robotic-assisted kidney transplantation
Shuncheng TAN ; Jianchun CUI ; Xun SUN ; Wei HU ; Yunchong ZHOU ; Yonglin SONG ; Shuxin LI ; Yinrui MA ; Yafei ZHANG
Organ Transplantation 2024;15(6):928-934
Objective To explore the learning curve of robotic-assisted kidney transplantation(RAKT).Methods The clinical data of 96 consecutive RAKT patients performed by the same surgical team were retrospectively analyzed.The arterial anastomosis time,venous anastomosis time,ureteral anastomosis time,hospital stay,and blood loss were selected as evaluation indicators.The learning curve of RAKT was analyzed using the cumulative sum(CUSUM),and the curve was divided into the learning improvement stage and the proficient mastery stage according to the learning curve.The learning curve was verified by comparing the general data and surgical data of patients in different learning stages,and the clinical efficacy of each stage was analyzed.Results The optimal fitting equation of the learning curve reached its peak at the 33rd case,which was the minimum number of surgeries required to master RAKT.There was no statistically significant difference in age,gender,dialysis type,previous abdominal surgery history,number of donor renal arteries,and preoperative serum creatinine between the learning improvement group and the proficient mastery group(all P>0.05).Compared with the learning improvement stage,the body mass index(BMI)was higher,and the number of right donor kidney was increased compared to the left donor kidney in the proficient mastery stage(both P<0.05).There were no significant differences in arterial anastomosis time,ureteral anastomosis time,postoperative serum creatinine,and complications between the two groups(all P>0.05).The iliac vessel dissection time,warm ischemia time,venous anastomosis time,blood loss,and hospital stay in the proficient mastery stage were superior to those in the learning improvement stage,with statistically significant differences(all P<0.05).Conclusions RAKT requires at least 33 cases to cross the learning curve.There is no difference in complications and recovery of transplant renal function between the learning improvement stage and the proficient mastery stage.
6.Effect of bluetongue virusinfection on type Ⅰ interferon response in BHK-21 cells
Shimei LUO ; Yunyi CHEN ; Qisha LI ; Yanmei ZHOU ; Yifei WANG ; Xinyu LIAO ; Xuer-Ou HU ; Yuanjian WEI ; Mengqin LI ; Meng ZHU ; Xun ZHANG ; Beirui CHEN ; Xianping MA ; Jiarui XIE ; Meiling KOU ; Haisheng MIAO ; Fang LI ; Huashan YI
Chinese Journal of Veterinary Science 2024;44(8):1639-1644,1690
Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.
7.Moxifloxacin treatment for Mycoplasma hominis meningitis in an extremely preterm infant
Wei-Ying MAO ; Jiang-Er LAN ; Ming-Yu GAN ; Xun-Jie ZHANG ; Hui YU ; Li-Yuan HU ; Rong ZHANG ; Yun CAO ; Mi-Li XIAO
Chinese Journal of Contemporary Pediatrics 2024;26(4):432-436
The patient,a male newborn,was admitted to the hospital 2 hours after birth due to prematurity(gestational age 27+5 weeks)and respiratory distress occurring 2 hours postnatally.After admission,the infant developed fever and elevated C-reactive protein levels.On the fourth day after birth,metagenomic next-generation sequencing of cerebrospinal fluid indicated a positive result for Mycoplasma hominis(9 898 reads).On the eighth day,a retest of cerebrospinal fluid metagenomics confirmed Mycoplasma hominis(56 806 reads).The diagnosis of purulent meningitis caused by Mycoplasma hominis was established,and the antibiotic treatment was switched to moxifloxacin[5 mg/(kg·day)]administered intravenously for a total of 4 weeks.After treatment,the patient's cerebrospinal fluid tests returned to normal,and he was discharged as cured on the 76th day after birth.This article focuses on the diagnosis and treatment of neonatal Mycoplasma hominis purulent meningitis,introducing the multidisciplinary diagnosis and treatment of the condition in extremely preterm infants.[Chinese Journal of Contemporary Pediatrics,2024,26(4):432-436]
8.Associations of short-term ambient particulate matter exposure and MTNR1B gene with triglyceride-glucose index:A family-based study
Huangda GUO ; Hexiang PENG ; Siyue WANG ; Tianjiao HOU ; Yixin LI ; Hanyu ZHANG ; Mengying WANG ; Yiqun WU ; Xueying QIN ; Xun TANG ; Jing LI ; Dafang CHEN ; Yonghua HU ; Tao WU
Journal of Peking University(Health Sciences) 2024;56(3):375-383
Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90%females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95%CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95%CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95%CI:0.004-0.076).The TyG index was 0.079(95%CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.
9.Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic.
Shun BAI ; Ming-Zhen LI ; Yang-Yang WAN ; Xue-Chun HU ; Yi-Xun LIU ; Xian-Hong TONG ; Tong-Hang GUO ; Lu ZONG ; Ran LIU ; Yuan-Qi ZHAO ; Ping XIANG ; Bo XU ; Xiao-Hua JIANG
Asian Journal of Andrology 2023;26(1):41-45
Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.
10.Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8.
Ying HU ; Shuxian WANG ; Lan WU ; Kai YANG ; Fan YANG ; Junfa YANG ; Shuang HU ; Yan YAO ; Xun XIA ; Yixin LIU ; Li PENG ; Jihong WAN ; Chuanpu SHEN ; Tao XU
Chinese Journal of Natural Medicines (English Ed.) 2023;21(9):670-681
Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.


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