1.Effects of emodin modulation of the HIF-1α/VEGF pathway on vascular endothelial cells damage in diabetic macroangiopathy rats
Qiu-Xiao ZHU ; Hui-Yao HAO ; Zi-Bo LIU ; Ming GAO ; Fang ZHANG ; Jing ZHOU ; Zhi-Hua HAO ; Li-Hui ZHANG ; Yong-Mei HAO
The Chinese Journal of Clinical Pharmacology 2024;40(6):859-863
Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)%,(6.28±0.20)%,(24.96±1.18)%,(12.36±0.49)%,(18.76±0.68)%and(4.59±0.26)%;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P<0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.
2.Metabolomic Analysis of Mesenteric Lymph Fluid in Rats After Alcohol Gavage
Yuan ZHANG ; Zi-Ye MENG ; Wen-Bo LI ; Yu-Meng JING ; Gui-Chen LIU ; Zi-Yao HAO ; Xiu XU ; Zhen-Ao ZHAO
Progress in Biochemistry and Biophysics 2024;51(9):2194-2209
ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg-1·d-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.
3.Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion
Zi-xin LIU ; Gao-jie XIN ; Yue YOU ; Yuan-yuan CHEN ; Jia-ming GAO ; Ling-mei LI ; Hong-xu MENG ; Xiao HAN ; Lei LI ; Ye-hao ZHANG ; Jian-hua FU ; Jian-xun LIU
Acta Pharmaceutica Sinica 2024;59(2):374-381
This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.
4.Research on the application of non-contact physiological and psychological detection in the analysis of long-term simulated weightlessness effects
Shuai DING ; Zi XU ; Qian RONG ; Shujuan LIU ; Zihao LIU ; Yuan WU ; Yao YU ; Zhili LI ; Cheng SONG ; Lina QU ; Hao WANG ; Yinghui LI
Space Medicine & Medical Engineering 2024;35(2):78-83,98
Objective Explore a non-contact physiological and psychological detection model based on facial video in simulations of weightlessness effects,research new methods for non-contact heart rate and negative mood state detection in long-term simulations of weightlessness effect analysis.Methods Construct a non-contact physiological and psychological data collection system for fusion analysis of visible light and thermal infrared videos.Collect physiological and psychological data of volunteers in the"Earth Star-Ⅱ"90-day head-down bed rest experiment.A non-contact heart rate detection model based on GCN facial multi-region feature fusion and a non-contact negative mood state detection model considering data reliability were constructed,and the effectiveness of the models were validated with finger clip heart rate and POMS-SF scale as labels.Results The experimental results show that the average difference in the Bland-Altman plot of the non-contact heart rate detection model is-1.26 bpm,and 96.3%of value error detection data falls within the 95%confidence interval,indicating a high consistency between the model detected heart rate and the finger clip heart rate.The non-contact negative mood state detection model achieves an accuracy of>0.85 for detecting tension,depression,anger,and fatigue.Features such as heart rate,AU06,eye gaze,and head pose were observed to be important to mood state detection.Conclusion Non-contact physiological and psychological detection methods not only can be utilized for long-term physiological analysis in simulations of weightlessness effects,but also provide a novel technical approach for on-orbit astronauts health assurance during long-term space flight in the future.
5.Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury
Hua Wei CAO ; Ting Ting JIANG ; Ge SHEN ; Wen DENG ; Yu Shi WANG ; Yu Zi ZHANG ; Xin Xin LI ; Yao LU ; Lu ZHANG ; Yu Ru LIU ; Min CHANG ; Ling Shu WU ; Jiao Yuan GAO ; Xiao Hong HAO ; Xue Xiao CHEN ; Ping Lei HU ; Jiao Meng XU ; Wei YI ; Yao XIE ; Hui Ming LI
Biomedical and Environmental Sciences 2024;37(5):494-502
Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.
6.Comparison of thermal ablation combined with synchronous TACE and TACE in liver metastasis of neuroendocrine tumors of different pathologic grades
Sothea YAV ; Hui-Yi SUN ; Fei-Hang WANG ; Dan-Yang ZHAO ; Zi-Hao HUO ; Yi CHEN ; Zhi-Ping YAN ; Ling-Xiao LIU
Fudan University Journal of Medical Sciences 2024;51(3):323-330,337
Objective To compare the efficacy and safety between thermal ablation combined with synchronous transcatheter arterial chemoembolization(TACE)and TACE in patients with liver metastasis of neuroendocrine tumors of different pathologic grades.Methods A retrospective analysis was performed on patients with liver metastases of neuroendocrine tumors admitted to Department of Interventional Radiology,Zhongshan Hospital,Fudan University from Nov 1,2006 to Jul 31,2022.The patients were divided into synchronous ablation group and TACE group according to treatment mode and subgroups according to pathological grade.The lesions were evaluated by postoperative imaging examination.The patients were followed up until Jul 31,2023,and surgery-related complications were recorded.The endpoint of prognosis were progression-free survival(PFS)and overall survival(OS).Results A total of 86 patients with neuroendocrine tumor were collected,including 34 patients in simultaneous ablation group and 52 patients in TACE group.According to WHO classification,21 patients at G1 stage,45 patients at G2 stage and 20 patients at G3 stage were included.No serious postoperative complications occurred in all patients.The median OS was 47.0(95%CI:31.2-62.8)months in the TACE group and 56.0(95%CI:8.3-73.4)months in the synchronous ablation group,with no statistical difference between the two groups(P=0.50).The median PFS was 18.0(95%CI:6.0-30.0)months in the TACE group and 29.0(95%CI:10.0-48.0)months in the synchronous ablation group,with no statistical difference between the two groups(P=0.22).Of the 45 patients at G2 stage,27 received TACE with a median OS of 47.0 months,and 18 received synchronous ablation with a median OS of 59.0 months,and there was no statistical difference between the two groups(P=0.45).The median PFS was 12.0 months in the TACE group and 32.0 months in the synchronous ablation group,and the difference between the two groups was statistically significant(P=0.03).Conclusion Comparing with TACE,simultaneous ablation can delay disease progression in patients with liver metastasis of neuroendocrine tumors to a certain extent and has good safety,especially for patients with liver metastases of neuroendocrine tumors with intermediate or low grade.
7.A retrospective study of occlusal reconstruction in patients with old jaw fractures and dentition defects
Ming-Chao DING ; Bo-Ya JING ; Jin SHI ; Liu YANG ; Xiang-Dong LIU ; Jing-Fu WANG ; Shuang QU ; Jia-Wu LIANG ; Zi-Hao TANG ; Jin-Long ZHAO ; Lei TIAN
Chinese Journal of Traumatology 2024;27(5):272-278
Purpose::This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects.Methods::Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct 3-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean ± standard deviation and compared using independent sample t-tests. Results::In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment.Conclusion::Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.
8.Design,numerical simulation and experimental study of novel oxygenator
Ming-Hao YUE ; Shi-Yao ZHANG ; Ji-Nian LI ; Hui-Chao LIU ; Zi-Hua SU ; Ya-Wei WANG ; Zeng-Sheng CHEN ; Shi-Hang LIN ; Jin-Yu LI ; Ya-Ke CHENG ; Yong-Fei HU ; Cun-Ding JIA ; Ming-Zhou XU
Chinese Medical Equipment Journal 2024;45(3):23-28
Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]
9.Comparison of Clinical Characteristics of JAK2,CALR and Tri-Negative Driving Mutant Type in Patients with Essential Thrombocythemia
Yu-Meng LI ; Er-Peng YANG ; Zi-Qing WANG ; De-Hao WANG ; Ji-Cong NIU ; Yu-Jin LI ; Jing MING ; Ming-Qian SUN ; Zhuo CHEN ; Wei-Yi LIU ; Yan LYU ; Xiao-Mei HU
Journal of Experimental Hematology 2024;32(1):197-201
Objective:To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia(ET).Methods:The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed.According to driver mutation type,patients were divided into JAK2 group,CALR group and triple-negative group.The sex,age,cardiovascular risk factors,thrombosis,splenomegaly,routine blood test and coagulation status of patients in three groups were analyzed.Results:Among 69 ET patients,46 cases were associated with JAK2 mutation,14 cases with CALR mutation,8 cases with triple-negative mutation,and one with MPL gene mutation.There were no significant differences in age and sex among the three groups(P>0.05).The highest thrombotic rate was 26.09%(12/46)in JAK2 group,then 12.5%(1/8)in triple-negative group,while no thrombotic events occurred in CALR group.The incidence of splenomegaly was the highest in JAK2 group(34.78%),while no splenomegaly occurred in triple-negative group.The white blood cell(WBC)count in JAK2 group was(9.00±4.86)× 109/L,which was significantly higher than(6.03±2.32)× 109/L in CALR group(P<0.05).The hemoglobin(Hb)and hematocrit(HCT)in JAK2 group were(148.42±18.79)g/L and(0.44±0.06)%,respectively,which were both significantly higher than(131.00±15.17)g/L and(0.39±0.05)%in triple-negative group(P<0.05).The platelet(PLT)in JAK2 group was(584.17±175.77)× 109/L,which was significantly lower than(703.07±225.60)× 109/L in CALR group(P<0.05).The fibrinogen(Fg)in JAK2 and triple-negative group were(2.64±0.69)g/L and(3.05±0.77)g/L,respectively,which were both significantly higher than(2.24±0.47)g/L in CALR group(P<0.05,P<0.01).The activated partial thromboplastin time(APTT)in triple-negative group was(28.61±1.99)s,which was significantly decreased compared with(31.45±3.35)s in CALR group(P<0.05).Conclusions:There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations.Among ET patients,JAK2 mutation is most common.Compared with CALR group,the thrombotic rate,WBC and Fg significantly increase in JAK2 group,while PLT decrease.Compared with triple-negative group,the incidence of splenomegaly and HCT significantly increase.Compared with CALR group,Fg significantly increases but APTT decreases in triple-negative group.
10.Advances in natural drug modulation of astrocytes to promote neural repair after ischemic stroke
Zi-Shan HUANG ; Ye-Hao ZHANG ; Jian-Xun LIU
Chinese Pharmacological Bulletin 2024;40(6):1013-1019
Astrocytes play a non-negligible role in the process of nerve injury and repair.China has abundant resources of natural drugs,and the research on the drug effects and mechanisms of astrocytes has been on rise recently,providing a rich basis and ideas for the treatment of ischemic stroke.In this paper,we de-scribe the effects of astrocytes on neural repair after ischemic stroke and the underlying mechanisms,as well as the role of nat-ural drugs in regulating this process and thus promoting repair.

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