1.Polydatin protects vascular endothelial cells by modifying the JAK2/STAT3 signaling pathway
Wenwen KONG ; Huizhen WEI ; Yuanying XU ; Wenjun SHA ; Jun LU ; Tao LEI
Acta Universitatis Medicinalis Anhui 2024;59(7):1201-1205,1212
Objective To study the protective effect of polydatin on lipopolysaccharide-induced injury of human umbilical vein vascular endothelial cells(HUVECs)through the protein Janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3)signaling pathway.Methods HUVECs were cultured in vitro,and 500 ng/ml LPS induced their injury and set as a model group;based on the model group,endothelial cells were inter-vened with different concentrations(10,20,and 40 μmol/L)of polydatin for 24 h,and set as polydatin low concentration group,polydatin medium concentration group,and polydatin high concentration group,respectively;a control group was set as another group.CCK-8,monocyte-endothelial cell adhesion,scratch and Transwell assays were used to detect cell viability,adhesion,migration and invasive ability;ELISA was used to detect interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)levels in the cell supernatant;Western blot was used to detect the expression of proteins related to the JAK2/STAT3 signaling pathway levels of JAK2/STAT3 signaling pathway relat-ed proteins.Results Compared with the control group,the model group showed decreased cell survival(P<0.01),increased cell adhesion,migration and invasion(P<0.001,P<0.05,P<0.01),increased levels of IL-6 and TNF-α in the cell supernatant(P<0.001),and increased levels of phosphorylation of JAK2 and STAT3 pro-teins in the cells(P<0.05).Compared with the model group,LPS damage to cells was attenuated after polydatin intervention,cell survival was increased in polydatin low-,medium-and high-concentration groups(P<0.05),cell adhesion,migration,and invasion decreased(P<0.05,P<0.05,P<0.001),IL-6 and TNF-α levels in cell supernatants decreased(P<0.05),and the levels of cellular JAK2 and STAT3 protein phosphorylation lev-els decreased(P<0.05).Conclusion Polydatin seems to reduce the inflammatory injury of human umbilical vein endothelial cells induced by LPS,reducing the secretion of inflammatory factors,and inhibiting the ability of cell ad-hesion,migration and invasion,which may be related to the down-regulation of JAK2/STAT3 signal pathway by polydatin.
2.Generation and characterization of humanized monoclonal antibody against human IFNAR1
Jiwan QIU ; Yong KONG ; Wei CHEN ; Lei XU ; Chunjie CAO ; Tao CHEN ; Yiliang WU
Journal of China Pharmaceutical University 2024;55(3):404-411
Type I interferons play an important role in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus(SLE).Monoclonal antibody shows therapeutic potential by blocking the signaling pathway.This study used recombinant human subunit 1 of the type I interferon receptor(IFNAR1)protein to immunize New Zealand white rabbits,and applied B cell cloning technology to screen and obtain rabbit parental antibodies.After humanization modification,QX006N was obtained.In vitro biological studies showed that QX006N could specifically bind to human IFNAR1 with an affinity of 108 pmol/L,and neutralize the type I interferon signaling pathway and this pathway mediated biological effects.This study provides a solid foundation for the development of antibody drugs targeting the type I interferon signaling pathway for the treatment of SLE.
3.Case 02 (2024): Acute ST-segment elevation myocardial infarction during pregnancy caused by coronary artery dissection: a case report
Lingying KONG ; Pengkang HE ; Jianping LI ; Dongxin WANG ; Tao HONG ; Yu SUN ; Qian CHEN ; Yumei WEI ; Hong ZHANG ; Huixia YANG
Chinese Journal of Perinatal Medicine 2024;27(3):226-232
This article presents a case of acute ST-segment elevation myocardial infarction (STEMI) in a pregnant woman caused by coronary artery dissection. The 41-year-old patient had undergone cardiac valve surgery at the age of 1 and had no risk factors such as hypertension, diabetes, smoking, alcohol use, or a family history of coronary artery disease. At 31 +1 weeks of gestation, she experienced sudden chest pain for 4 hours and was emergently referred to Peking University First Hospital on June 1, 2021. Electrocardiogram revealed ST-segment elevation in leads I, aVL, and V 2 to V 6. Biochemical assays showed elevated levels of high-sensitivity cardiac troponin I and creatine kinase-MB. Echocardiography indicated segmental ventricular wall motion abnormalities (apical) and reduced left ventricular function, confirming the diagnosis of acute anterior wall STEMI. The patient promptly underwent emergency coronary angiography and percutaneous coronary intervention and confirmed coronary artery dissection. Postoperative care included antiplatelet, anticoagulation, and supportive treatment. At 34 +3 weeks of gestation, with the condition of acute anterior wall STEMI being relatively stable, a cesarean section was successfully performed. Regular cardiology follow-ups were scheduled postpartum, and cardiac function was normal in two years after discharge.
4.Application of early clinical exposure concept-guided question-answer teaching combined with ORTCC model in endocrine teaching reform
Jiajie WEI ; Xiangyi KONG ; Bin ZHANG ; Fang FANG ; Tianxia QIN ; Hong TAO
Chinese Journal of Medical Education Research 2024;23(5):688-691
Objective:To explore the application of the early clinical exposure concept-guided question-answer teaching model combined with the ORTCC (objectives, rules, training, check, and culture) model in endocrine teaching reform.Methods:Sixty-two students who interned at Beijing Anzhen Hospital of Capital Medical University from August 2022 to August 2023 were divided into control group and observation group according to the order of student number, with 31 students in each group. The control group received traditional teaching, while the observation group received early clinical exposure concept-guided question-answer teaching combined with the ORTCC model. At the end of the internship, the two groups were compared in terms of theoretical and practical assessment scores and comprehensive competency assessment scores. SPSS 22.0 was used to perform the t-test. Results:The theoretical assessment score of the control group was (87.00±3.86) points, while that of the observation group was (91.26±4.34) points, with a statistically significant difference between the two groups ( t=4.09, P<0.001). The observation group also showed significantly higher scores of clinical practice assessment and comprehensive competency assessment than the control group ( P<0.05). Conclusions:The combination of question-answer teaching guided by the early clinical exposure concept and the ORTCC model is helpful for endocrine interns to master theoretical knowledge and acquire clinical practical skills and comprehensive abilities, effectively improving the quality of internship teaching.
5.Study on the Expression Level of Magnesiun Transporter Protein 1 in Peripheral Blood T Lymphocytes of Patients with Systemic Lupus Erythematosus and Its Clinical Value
Tao KONG ; Shun RAO ; Wei ZHU ; Kanha YU ; Chao YU
Journal of Modern Laboratory Medicine 2024;39(3):157-163
Objective To investigate the expression of magnesiun transporter 1 protein(MagT1)in peripheral blood T lymphocytes of patients with systemic lupus erythematosus(SLE),and elucidate its clinical significance.Methods A total of 79 SLE patients admitted to the People's Hospital of Xishuangbanna Dai Autonomous Prefecture from January 2019 to June 2021 were selected as the study subjects,and SLE patients were divided into moderate to severe group(SLEDAI ≥ 10,n=32)and mild group(SLEDAI<10,n=47),according to SLE disease activity index(SLEDAI)score.Another 40 healthy patients who underwent physical examinations during the same period were selected as control group.The levels of clinical biochemical and serum immune-related indexes were recorded.The expressions of MagT1 mRNA and protein in peripheral blood T lymphocytes were detected by quantitative real-time PCR(qRT-PCR)and Western Blot methods.The correlation between the expression of MagT1 protein in peripheral blood T lymphocytes and biochemical and immunity-related indexes was analyzed by Pearson correlation analysis.Receiver working characteristic(ROC)curve was drawn to analyze the diagnostic value of MagT1 protein expression of peripheral blood T lymphocytes in diagnosing SLE and its severity.Results Compared with the control group,the expression levels of MagT1 mRNA[0.65(0.36,0.99),0.23(0.07,0.36)vs 1.20(0.83,1.37)]and MagT1 protein[0.35(0.22,0.42),0.22(0.15,0.27)vs 0.53(0.40,0.63)]of peripheral blood T lymphocytes in the mild group and the moderate to severe group were reduced,with significant differences(Z=5.247,7.078;5.128,7.257,all P<0.05).Compared with the mild group,the expression levels of MagT1 mRNA[0.65(0.36,0.99)vs 0.23(0.07,0.36)]and protein[0.35(0.22,0.42)vs 0.22(0.15,0.27)]of peripheral blood T lymphocytes in the moderate to severe group were reduced,with significant differences(Z=5.169,3.599,all P<0.05).Pearson correlation results showed that MagT1 protein expression in peripheral blood T lymphocytes was positively correlated with serum hemoglobin(HGB),complement 3(C3)and C4 levels(r=0.496,0.637,0.588,all P<0.05),but was negatively correlated with serum erythrocyte sedimentation rate(ESR),hypersensitive C-reactive protein(hs-CRP),IgG levels and SLEDAI(r=-0.598,-0.476,-0.646,-0.514,all P<0.05).The results of the ROC curve showed that the area under the curve in diagnostic SLE for the expression level of peripheral blood T lymphocyte MagT1 protein was 0.893(95%CI:0.838~0.948),with a sensitivity and a specificity of 90.0%and 67.1%,respectively,and the area under the curve in diagnostic SLE severity was 0.739(95%CI:0.631~0.848),with a sensitivity and a specificity of 57.4%and 84.4%,respectively.Conclusion The expressions of peripheral blood T lymphocyte and MagT1 were down regulated in SLE patients,and they had a negative trend with the severity of SLE.They may have a certain diagnostic value for the diagnosis and severity of SLE.
6.Investigation of ABO and RhD blood groups in childbearing age people in rural areas of Yunnan Province.
Zheng Yuan XIE ; Guang CAO ; Tao WANG ; Cai KONG ; Yi Xiao LI ; Wei Lei ZU ; Zi Gao ZHAO ; Han Feng YE
Chinese Journal of Preventive Medicine 2023;57(1):52-57
The participants in this study were 20-49 years old rural childbearing age people who received the National Free Preconception Health Examination Project (NFPHEP) in Yunnan Province during 2013 to 2019. The proportion of ABO and RhD blood groups among different ethnic groups and different areas were calculated. The proportion of 2 748 131 participants with blood group A phenotype was highest (32.60%), followed by O (30.60%), B (27.33%) and AB (9.47%). In the RhD blood system, the proportion of the RhD positivity (RhD+) and RhD negativity (RhD-) group were 99.29% and 0.71% respectively. The proportions blood groups were significantly different among ethnic groups and areas (all P<0.001). Among 18 ethnic groups with more than 3 000 participants, Yao (42.75%), Bouyei (40.58%) and Dai (40.37%) ethnic groups had higher proportion of blood group O phenotype than other ethnic groups. Wa ethnic groups had highest proportion of the A (40.15%) and AB phenotypes (11.23%). Miao ethnic group (34.70%) and Lahu ethnic group (34.42%) had higher proportion of blood group B phenotype than other ethnic groups. Wa ethnic group had the highest proportion of RhD-group (1.88%). In all 16 prefectures of Yunnan, the proportion of blood group O phenotype was highest in Xishuangbanna Dai Autonomous Prefecture (40.27%). Baoshan city (36.39%), Lincang city (36.22%) and Dali Bai autonomous prefecture (36.06%) had higher proportion of blood group A phenotype than other regions. Diqing Tibetan Autonomous Prefecture (30.83%) and Qujing city (30.48%) had higher proportion of blood group B phenotype than other areas, while Zhaotong city had a highest proportion of blood group AB phenotype (11.19%). The proportion of RhD-group was highest in Honghe hani and Yi nationality autonomous prefecture(1.37%). The A RhD+(39.36%), A RhD-(0.78%), AB RhD+(11.03%), AB RhD-(0.20%) and O RhD-(0.48%) blood groups were higher proportion in Wa ethnic group than in other ethnic groups (P<0.001).
Adult
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Humans
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Middle Aged
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Young Adult
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Blood Group Antigens
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China
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Ethnicity
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Rural Population
7.Imaging classification and analysis of the diagnosis and treatment of infected pancreatic necrosis:a report of 126 cases.
Tian Qi LU ; Li Ren SHANG ; Fan BIE ; Yi Lin XU ; Yu Hang SUI ; Guan Qun LI ; Hua CHEN ; Gang WANG ; Rui KONG ; Xue Wei BAI ; Hong Tao TAN ; Yong Wei WANG ; Bei SUN
Chinese Journal of Surgery 2023;61(1):33-40
Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ2 test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ2=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ2=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.
Male
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Female
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Humans
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Retrospective Studies
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Pancreatitis, Acute Necrotizing/complications*
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Acute Disease
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Intraabdominal Infections/complications*
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Necrosis/complications*
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Treatment Outcome
8.Application of precision-cut lung slice technology to study the role of DDR2 in pulmonary fibrosis.
Xi-Hui HUANG ; Tao CHENG ; Ling MOU ; Xin BO ; Xin-Ru WEI
Acta Physiologica Sinica 2023;75(4):515-520
Pulmonary fibrosis is a severe lung interstitial disease characterized by the destruction of lung tissue structure, excessive activation and proliferation of fibroblasts, secretion and accumulation of a large amount of extracellular matrix (ECM), and impaired lung function. Due to the complexity of the disease, a suitable animal model to mimic human pulmonary fibrosis has not yet been established. Precision-cut lung slice (PCLS) has been a widely used in vitro method to study lung physiology and pathogenesis in recent years. This method is an in vitro culture technology at the level between organs and cells, because it can preserve the lung tissue structure and various types of airway cells in the lung tissue, simulate the in vivo lung environment, and conduct the observation of various interactions between cells and ECM. Therefore, PCLS can compensate for the limitations of other models such as cell culture. In order to explore the role of discoidin domain receptor 2 (DDR2) in pulmonary fibrosis, Ddr2flox/flox mice were successfully constructed. The Cre-LoxP system and PCLS technology were used to verify the deletion or knockdown of DDR2 in mouse PCLS. Transforming growth factor β1 (TGF-β1) can induce fibrosis of mouse PCLS in vitro, which can simulate the in vivo environment of pulmonary fibrosis. In the DDR2 knock down-PCLS in vitro model, the expression of various fibrosis-related factors induced by TGF-β1 was significantly reduced, suggesting that knocking down DDR2 can inhibit the formation of pulmonary fibrosis. The results provide a new perspective for the clinical study of DDR2 as a therapeutic target in pulmonary fibrosis.
Animals
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Humans
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Mice
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Discoidin Domain Receptor 2/metabolism*
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Fibroblasts/pathology*
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Fibrosis
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Lung/pathology*
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Pulmonary Fibrosis/metabolism*
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Transforming Growth Factor beta1/metabolism*
9.Emerging vaccine nanotechnology: From defense against infection to sniping cancer.
Chan FENG ; Yongjiang LI ; Bijan Emiliano FERDOWS ; Dylan Neal PATEL ; Jiang OUYANG ; Zhongmin TANG ; Na KONG ; Enguo CHEN ; Wei TAO
Acta Pharmaceutica Sinica B 2022;12(5):2206-2223
Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation, antigen assembly, and antigen presentation; they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal. In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.
10.Construction of a quantitative diagnosis model for predicting the nature of thyroid nodules based on multi-modality ultrasound images
Yi TAO ; Peng ZHAO ; Hanqing KONG ; Quan DAI ; Lei ZHANG ; Ziyao LI ; Weidong YU ; Tianci WEI ; Jiawei TIAN
Chinese Journal of Ultrasonography 2022;31(5):420-426
Objective:To construct a quantitatively diagnostic nomogram model by analyzing the clinical information of patients and the features of multi-modality ultrasound images of thyroid lesions, so as to preoperatively predict the malignant probability of suspicious thyroid nodules and provide effective references for clinical decision-making.Methods:A total of 933 patients, 1 121 thyroid nodules of C-TIRADS 3-5 categories, who underwent surgery in the Second Affiliated Hospital of Harbin Medical University from September 1, 2020 to June 10, 2021 were collected. The nodules were randomly divided into training ( n=897) and test groups ( n=224) in 8∶2 ratio. Finally, the diagnostic performance was evaluated by area under the curve (AUC). Results:①After preliminary screening by univariate analysis, multivariate analysis showed that age, echogenicity, orientation, echogenic foci, margin, posterior features, and elastic score were significantly correlated with benign and malignant nodules (all P<0.001), and the difference of halo between benign and malignant nodules was also statistically significant ( P=0.012). ②The AUC of nomogram was up to 0.903(95% CI=0.862-0.944) in the test set, and 0.889(95% CI=0.832-0.946) and 0.960(95% CI=0.925-0.994) in nodules with maximum diameter of ≤10 mm and of >10 mm respectively, which showed high diagnostic performance. Conclusions:The nomogram model could accurately differentiate malignant from benign thyroid nodules preoperatively, with the highest diagnostic performance for the nodules with maximum diameter of >10 mm, and effectively avoid the unnecessary fine-needle biopsy and surgical operation.


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