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.Computer aided design of 3D dental segmentation and its application scenarios
Jiali CUI ; Minhui HUANG ; Donglin LIU ; Ruiming JIA ; Han LI
Chinese Journal of Tissue Engineering Research 2024;28(2):252-257
BACKGROUND:Traditional 3D dental segmentation methods usually utilize predefined spatial geometric features,such as curvature and normal vectors,as the reference information for tooth segmentation. OBJECTIVE:To propose an algorithm for complex 3D dental segmentation and deeply explore the correlation between segmentation results and application scenarios. METHODS:A 3D dental segmentation algorithm based on dual stream extraction of structural features and spatial features was established,and the modular design of split flow was used to avoid feature confusion.Among them,the attention mechanism on the structural feature flow was used to capture the fine-grained semantic information required for tooth segmentation,and the Tran Net based on the spatial feature flow was used to ensure the robustness of the model to complex tooth and jaw segmentation.This algorithm verified its effectiveness and reliability based on clinical datasets including healthy dental jaws and complex dental jaws such as missing teeth,malocclusion and dentition crowding.The segmentation performance of the model was measured in terms of overall accuracy,mean intersection over union,and directional cut discrepancy. RESULTS AND CONCLUSION:The overall segmentation accuracy of this algorithm in the clinical data set is 97.08%,and the segmentation effect is superior to that of other competitive methods from the qualitative and quantitative perspectives.It is verified that the structural feature flow designed in this paper can extract more precise local details of tooth shape from coordinate and normal information by constructing an attention aggregation mechanism,and the spatial feature flow designed in this paper can ensure the robustness of the model to complex teeth such as missing teeth,dislocated teeth,and crowded dentition by constructing a transformation network(Tran Net).Therefore,this tooth segmentation algorithm is highly reliable for clinicians'practical reference.
3.Efficacy and safety comparison of lacosamide and carbamazepine in the treatment of adult patients with newly diagnosed epilepsy
Xiaqing GUO ; Guofei LI ; Yuhua SUN ; Donglin ZHENG
China Pharmacy 2024;35(4):464-467
OBJECTIVE To compare the efficacy and safety of lacosamide (LCM) and carbamazepine (CAR) as monotherapy in the treatment of adult patients with newly diagnosed epilepsy. METHODS By methods of retrospective analysis, 84 adult patients with newly diagnosed epilepsy, were admitted to the Department of Neurology, Huaihe Hospital of Henan University during Sept. 2020-Jun. 2022, were divided into the control group (40 cases, receiving CAR treatment) and the observation group (44 cases, receiving LCM treatment) according to different medication regimens. Total response rate, epilepsy seizure frequency, blood lipid levels, and the occurrence of adverse events (AEs) of patients were compared between the 2 groups. RESULTS In the first month after treatment, there was no statistically significant difference in the total response rate between the observation group (63.64%) and the control group (55.00%, P>0.05); the frequency of epilepsy seizure in both groups was significantly reduced compared to before treatment (P<0.05), but there was no statistically significant difference between 2 groups (P>0.05). In the third month after treatment, the total response rate of the observation group (90.91%) was significantly higher than control group (67.50%, P<0.05); the frequencies of epilepsy seizure in both groups were significantly reduced compared to before treatment, and the observation group was significantly lower than the control group (P<0.05). In the third month after treatment, the levels of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholestrol (LDL-C) in the control group and the level of LDL-C in the observation group were significantly higher than before treatment, and the levels of TC, TG and LDL-C in the observation group were significantly lower than those in the control group (P<0.05). There was no statistically significant difference in the incidence of AEs between the observation group (15.91%) and the control group (17.50%, P>0.05). CONCLUSIONS Both LCM and CAR have certain effects in the treatment of newly diagnosed epilepsy in adults, which can reduce the frequency of epilepsy seizure in patients and have comparable safety. Meanwhile, LCM has better long-term efficacy than CAR in treating newly diagnosed epilepsy in adults, and its impact on the patient’s blood lipid is smaller than CAR.
4.Characteristics of Oral Breath Odor Map of Chronic Atrophic Gastritis Patients with Dampness-Heat Syndrome: A Cross-Sectional Study
Xuejuan LIN ; Yanyu HUANG ; Long ZHU ; Donglin CAO ; Shanshan DING ; Xinghui LI ; Yingying HU ; Meng LAN ; Weirong HUANG
Journal of Traditional Chinese Medicine 2024;65(16):1687-1694
ObjectiveTo explore the recognition of oral breath odor map of chronic atrophic gastritis (CAG) patients with dampness-heat syndrome by electronic nose technique. MethodsPatients with chronic gastritis were recruited, including 60 cases in CAG group of dampness-heat syndrome, 50 cases in CAG group of non-dampness-heat syndrome, 60 cases in chronic non-atrophic gastritis (CNAG) group of dampness-heat syndrome, 50 cases in CNAG group of non-dampness-heat syndrome, and 30 cases of healthy volunteers were selected to set up the health control group. Ten cases in the CAG dampness-heat group and 50 cases in the CAG non-dampness-heat group were selected to form the CAG group, and 10 cases in CNAG dampness-heat group and 50 cases in CNAG non-dampness-heat group were selected to form the CNAG group. In addition to the health control group, the remaining patients were tested for Helicobacter pylori (Hp); the electronic nose (GISXM-MQWA01) was used to collect the oral breath odor of all the participants to draw the mapping, and amplitudes and slopes of each curve (including curves A, B, C, D, E, F, G, H, I, J) of the oral odor mapping of health control group, CAG group, CNAG group, CAG dampness-heat group, CAG non-dampness-heat group, and CNAG dampness-heat group was compared. The modified transformer model was used to classify the odor mapping characteristics, and the confusion matrix method was used to evaluate the classification model, with metrics including accuracy and area under ROC curve (AUC). ResultsThe Hp positivity rate in CAG dampness-heat group was 80.00% (48/60), CAG non-dampness-heat group was 62.00% (31/50), CNAG dampness-heat group was 46.67% (28/60), and CNAG non-dampness-heat group was 42.00% (21/50); the difference in Hp positivity rate between CAG dampness-heat group and CAG non-dampness-heat group was statistically significant (P<0.05). The amplitudes of response curves A, B, C, D, F, G, and I, and slopes of A and F in the odor mapping of the CAG group were lower than those in health control group, while the amplitude and slope of curve E were higher than those in the health control group and CNAG group (P<0.05 or P<0.01); The amplitude of the response curves A, B, C, D, F, G, and I, and slopes of A, D, and F in the CNAG group were lower than those in the health control group (P<0.05 or P<0.01). The amplitude of response curve D and slope of response curve J in the odor mapping of the CAG dampness-heat group were higher than those in CNAG dampness-heat group, the amplitude of curve F was lower than that in CAG non-dampness-heat group, and the amplitude of curve H and slopes of curve A, H, and J were higher than those in CAG non-dampness-heat group (P<0.05). The recognition accuracy of CAG group and health control group reached 77.78%, AUC = 0.88; the recognition accuracy of CAG group and CNAG group was 69.44%, AUC = 0.61; the recognition accuracy of CAG dampness-heat group and CAG non-dampness-heat group reached 75.8%, AUC=0.70. ConclusionElectronic nose technology can make a more accurate identification of the oral breath odor in CAG patients with dampness-heat syndrome, with a decrease in the amplitude of the curve F and an increase in the amplitude of the curve H and in the slopes of the curves A, H, and J may as the characteristics of their odor mapping.
5.Establishment of patent ductus arteriosus model in Bama miniature pigs using autogenous jugular vein
Jian LI ; Wenchao LI ; Fengwen ZHANG ; Donglin ZHUANG ; Peijian WEI ; Hang LI ; Min ZHANG ; Wenbin OUYANG ; Xiangbin PAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(12):1832-1837
Objective To explore the method and feasibility of establishing patent ductus arteriosus (PDA) model in Bama miniature pig by using autologous jugular vein, and to provide a large animal model for the development of PDA occluder and the study of pulmonary hypertension associated with congenital heart disease. Methods Five male Bama miniature pigs weighing about 45 kg were selected to gain the PDA model of the autogenous jugular vein, which was fixed by glutaraldehyde and anastomosed between the ascending aorta and the main pulmonary artery. The patency of PDA was confirmed by echocardiography and angiocardiography immediately and one week after the operation. Two animals were selected to undergo transcatheter closure of PDA via femoral vein 1 week after the operation, and the rest were euthanized to obtain PDA and lung tissue for pathological examination. Results The PDA model was successfully established in all five animals with a success rate of 100.0%. Immediately and 1 week after the operation, echocardiography and angiography showed that PDA blood flow was unobstructed, and hematoxylin-eosin staining showed that PDA endothelialization was good. One week after the operation, two animals were successfully treated with transcatheter femoral vein occlusion. The pathological examination of lung tissue showed thickening of the intima and muscular layer of pulmonary arterioles, thickening of pulmonary interstitium and infiltration of neutrophils. Conclusion It is safe and feasible to establish a large animal model of PDA by using autogenous jugular vein anastomosis between the ascending aorta and the main pulmonary artery. The model can be used for the development of PDA interventional occlusive devices and the pathophysiological study of congenital heart disease-related pulmonary hypertension.
6.Efficacy and safety of rhTPO combined with eltrombopag in treating persistent thrombocytopenia after allo-HSCT
Gang LI ; Pan PAN ; Xin CHEN ; Donglin YANG ; Aiming PANG ; Erlie JIANG ; Sizhou FENG ; Mingzhe HAN
Journal of Leukemia & Lymphoma 2024;33(8):456-461
Objective:To investigate the therapeutic effect and safety of recombinant human thrombopoietin (rhTPO) combined with low-dose eltrombopag in the treatment of persistent thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective case series study was conducted. The retrospective analysis was conducted on the clinical data of 20 patients diagnosed with post-allo-HSCT thrombocytopenia at Blood Diseases Hospital of Chinese Academy of Medical Sciences from January 2018 to June 2021. All patients didn't meet the platelet implantation criteria [without the platelet count (Plt) ≥20×10 9/L for a consecutive period of 7 days and discontinuation of platelet transfusion] after transplantation, and they received subcutaneous injections of rhTPO (15 000 U) once daily and oral administration of eltrombopag (50 mg) once. Treatment efficacy was defined as maintaining Plt≥20×10 9/L for a consecutive period of 7 days after treatment and discontinuation of platelet transfusion; treatment inefficacy was defined as Plt<20×10 9/L after treatment or continuation of platelet transfusion. The therapeutic effect of rhTPO combined with low-dose eltrombopag was analyzed; the adverse reactions were evaluated; the clinical characteristics were compared between the effective treatment group and ineffective treatment group; the overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan-Meier method between the effective treatment group and ineffective treatment group. Results:Among the 20 patients, 9 were diagnosed with acute myeloid leukemia (AML), 5 with acute lymphoblastic leukemia (ALL), 4 with myelodysplastic syndromes (MDS), and 2 with severe aplastic anemia (SAA); 10 cases were primary failure of platelet recovery (PFPR), and 10 cases were secondary failure of platelet recovery (SFPR). The median time [ M ( Q1, Q3)] from transplantation to initiation of treatment was 79 days (50 days, 89 days), and the median duration of treatment was 19.5 days (15 days, 30 days). Of the total cohort, treatment was effective in 13 cases (65.0%, 8 cases of PFPR, 5 cases of SFPR), while 7 patients (35.0%) showed no response to treatment. The median time to achieve the therapeutic response among responders was 10 days (7 days, 19 days). During the combination treatment, 5 patients experienced elevated transaminase levels exceeding more than 2.5 times the upper limit of normal or bilirubin levels surpassing twice that limit. No instances of adverse reaction-related arterial thrombosis, myelofibrosis, or primary disease relapse occurred within this patient cohort. Megakaryocyte counts in the effective treatment group before combination treatment were higher than that in the ineffective treatment group, and the difference was statistically significant [14 (10, 20) vs. 2.5 (2, 4); Z = -2.33, P = 0.017]; Notably, no statistically significant differences were identified when comparing the compositions of gender, type of underlying diseases, human leukocyte antigen matching degree, blood type of donor and recipient, conditioning regimen use of antithymocyte globulin, quantity of CD34 + cells transfused, type of thrombocytopenia, acute graft-versus-host disease, fungal or bacterial infections, and viral infections between the two groups (all P > 0.05). The 1-year OS rates for the effective and ineffective treatment groups were 100.0% and 42.9%, respectively, and the difference in OS between the two groups was statistically significant ( P = 0.001). The 1-year DFS rates for the effective and ineffective treatment groups were 92.3% and 28.6%, respectively, and the difference in DFS between the two groups was statistically significant ( P = 0.003). Conclusions:The combination of rhTPO and low-dose eltrombopag has demonstrated certain therapeutic efficacy and good safety in the treatment of persistent thrombocytopenia after allo-HSCT.
7.Research progress of MAVS in viruses evading host natural immunity
Donglin BI ; Xiaoli YANG ; Dongliang YANG ; Fangcheng LIU ; Xiaowen ZHANG ; Qiongyi LI ; Jialin BAI
Chinese Journal of Immunology 2024;40(11):2452-2457,2464
Innate immunity is the first line of the host cell defensing against viral infection,in which the pattern recognition re-ceptors(PRRs)such as Toll-like receptors(TLRs)and retinoic acid induces gene Ⅰ-like receptors(RLRs)play an important role.After virus infection,mitochondrial antiviral signaling protein(MAVS)in PRRs-mediated signaling pathway,which are of the com-mon linker molecule for downstream signal transmission,can receive signals transmitted by upstream TLR and RIG-Ⅰ,activate down-stream NF-κB and IRF3/7 signaling pathways leading to the activation of interferon(IFN)expression.Therefore MAVS acts as a bridge in the innate immune signaling pathway.More and more studies have shown that viruses have evolved a series of mechanism to escape the innate immune response over the long course of their evolution,and evaded the host's antiviral immune response by interfer-ing with multiple sites in the MAVS-mediated signaling pathway so as to complete its own replication and proliferation.In this paper,the role of MAVS in IFN-Ⅰ pathway and its latest research progress in the mechanism of anti-DNA viruses and anti-RNA viruses reac-tion are reviewed,providing theoretical basis for further studying the detailed mechanism of anti-virus of MAVS.
8.Effect of Pterostilbene Regulating Nuclear Factor E2-Related Factor 2 on Apoptosis of Colon Cancer Cells in Vitro
Xuehui SHI ; Chongxi FAN ; Quanlong YANG ; Xiaoying WANG ; Donglin ZHAO ; Manhua LI ; Xueliang WU ; Jianchun FAN ; Shoubin NING
Acta Academiae Medicinae Sinicae 2024;46(4):482-489
Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2(Nrf2)in the process of pterostilbene acting on LoVo cells.Methods LoVo cells were treated with different concentrations(5,10,20,40,60,80,100 panol/L)of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Tran-swell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochon-drial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlo-rofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic pro-teins(Bcl2 and Bax)were determined by Western blotting.In addition,cell viability,Nrf2 expression,and ap-optosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane.Results Compared with the control group,40,60,80,100 μmol/L pterostilbene reduced the viability of LoVo cells(P=0.014,P<0.001,P<0.001,P<0.001).Pterostilbene at 5,10,20 μmol/L did not show effects on cell viability but inhibited cell migration(P=0.008,P<0.001,P<0.001)and invasion(all P<0.001).Pterostilbene at 40,60,80 μmol/L increased apoptosis(P=0.014,P<0.001,P<0.001),promoted mitochondrial membrane potential depolarization(P=0.026,P<0.001,P<0.001)and reactive oxygen species accumula-tion(all P<0.001),and down-regulated the expression of phosphorylated Nrf2(P=0.030,P<0.001,P<0.001),heme oxygenase 1(P=0.015,P<0.001,P<0.001),and Bc12(P=0.039,P<0.001,P<0.001)in LoVo cells.Pterostilbene at 60,80 μmol/L down-regulated Nrf2 expression(P=0.001,P<0.001)and up-regulated Bax expression(both P<0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability(P<0.001),apoptosis(P<0.001),and Nrf2 expression(P=0.022).Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.
9.Effect of TACE with drug-loaded microspheres versus with iodinated oil emulsion on liver fibrosis
Daqian HAN ; Hao LI ; Manzhou WANG ; Chao LIANG ; Jiacheng WANG ; Wenze XU ; Yangyang NIU ; Donglin KUANG ; Jianzhuang REN ; Xuhua DUAN
Chinese Journal of Hepatobiliary Surgery 2024;30(10):738-743
Objective:To compare the effects of drug-loaded microsphere TACE (D-TACE) and iodinated oil emulsion TACE (cTACE) on liver fibrosis in the treatment of advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 113 patients with HCC treated with D-TACE or cTACE at the First Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were retrospectively analyzed, including 96 males and 17 females, aged (56.8±9.8) years old. According to treatment protocol, patients were divided into two groups: the D-TACE group ( n=57) and the cTACE group ( n=56). Liver fibrosis panel, fibrosis index (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared between the groups at four timepoints: pre-treatment, one month after the first TACE, one month after the second TACE, and 12 months after the first TACE. Follow-ups were conducted through outpatient visits or telephone reviews to assess patient survivals. Data including the progression-free survival (PFS) and number of TACE sessions were compared between the two groups. Results:The D-TACE group received 2.84±1.12 sessions of treatment during the observation period, compared to 4.05±1.44 sessions of cTACE group ( t=4.94, P<0.001). The median PFS in D-TACE and cTACE groups were 10.0 and 5.0 months, respectively ( P<0.001). At one month after the second TACE and at 12 months after the first TACE, patients in cTACE group had a higher serum levels of fibrosis markers including hyaluronic acid, type IV collagen, type III procollagen N peptide and laminin than those in D-TACE group (all P<0.05). At the same timepoints, patients in cTACE group also had higher APRI, FIB-4 and LSM than those in D-TACE group (all P<0.05). Conclusion:Compared to cTACE, patients in D-TACE group received fewer sessions of treatment during the first year after initial TACE, and the degree of liver fibrosis was also lower in D-TACE group.
10.Clinical effect of in vitro fenestration on reconstruction of left subclavian artery in endovascular treatment of aortic dissection
Donglin LI ; Lufeng CHEN ; Rongbin LI ; Xudong CAI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(03):403-409
Objective To investigate the effect of in vitro fenestration on reconstruction of left subclavian artery in endovascular treatment of aortic dissection. Methods A total of 89 patients with aortic dissection involving left subclavian artery were treated by endovascular treatment in the Second Affiliated Hospital of Fujian Medical University from February 2017 to January 2020. There were 44 patients in the test group, including 36 males and 8 females, with an average age of 58.02±13.58 years. There were 45 patients in the control group, including 35 males and 10 females, with an average age of 54.10±12.32 years. The left subclavian artery was reconstructed by in vitro fenestration in the test group and by chimney technique in the control group. The clinical data were compared between the two groups. Results The operation time of the test group was longer than that of the control group (126.16±7.53 min vs. 96.49±6.52 min, P<0.01). The median follow-up time was 31 (13-48) months. The incidence of endoleak in the test group (4.7%) was lower than that in the control group (18.6%, P=0.04) during the follow-up. There was no statistical difference in the incidence of stroke, myocardial infarction, false lumen thrombosis, retrograde aortic dissection or left subclavian artery occlusion between the two groups (P>0.05). Conclusion In vitro fenestration for reconstructing left subclavian artery in thoracic endovascular aortic repair of aortic dissection is safe and feasible, which is worthy of further clinical promotion.


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