1. Involvement of intracellular organelle stress, autophagy and ferroptosis in cobalt chloride-induced vascular smooth muscle cell injury
Yan LEI ; Xiaoyong PENG ; Tao LI ; Liangming LIU ; Mengsheng DENG ; Dongdong ZHANG ; Yingguo ZHU ; Jianmin WANG ; Zhaoxia DUAN ; Guangming YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(1):1-10
AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.
2.Diagnostic value of Treponema pallidum antibody index detected by electrochemiluminescence immunoassay in neurosyphilis
Sirui WU ; Yuanfang WANG ; Lan LUO ; Jielun DENG ; Dongdong LI ; Yi XIE
Chinese Journal of Microbiology and Immunology 2024;44(6):545-552
Objective:To evaluate the value of Treponema pallidum ( Tp)-specific antibody index in the diagnosis, staging, and typing of neurosyphilis (NS). Methods:Fifty patients diagnosed with NS at the West China Hospital of Sichuan University from March 2020 to December 2022 were recruited as the experimental group, and 50 non-NS syphilis patients were enrolled during the same period as the control group. Cerebrospinal fluid (CSF) and matched serum samples along with clinical data were collected. Clinical and Laboratory Standards Institute (CLSI) EP06-Ed2 file was used to analyze the linear range of electrochemiluminescence immunoassay for Tp-specific antibody detection, and the Tp antibody index was calculate for all subjects. The correlation of Tp antibody index, IgG index, IgG synthesis rate, and albumin quotient with other clinical indicators was evaluated by the coefficient of correlation, and the diagnostic efficacy of these indicators in NS was analyzed using the receiver operating characteristic (ROC) curve. Results:All the deviations from linearity of electrochemiluminescence immunoassay for detecting Tp antibodies in serum and CSF samples were within the allowable deviation from linearity. Compared with the non-NS group, the NS group showed a significant increase in the Tp antibody index ( P<0.05), with no significant differences observed among the groups of different subtypes, severity, or receiving treatment or not ( P>0.05). Tp antibody index, IgG index, and IgG synthesis rate were positively correlated with serum Tp antibody, CSF Tp antibody, trace protein, and nucleated cell count ( P<0.05). Taking 14.99 as the cut-off value for NS diagnosis, the diagnostic sensitivity of Tp antibody index was 74.0% (95%CI: 60.5%-84.1%), and the specificity was 94.0% (95%CI: 83.8%-98.4%), with the area under the ROC curve of 0.897, which was larger than that of albumin quotient, IgG index, and IgG synthesis rate. Conclusions:This study finds a significant increase in the Tp antibody index in NS patients with good diagnostic sensitivity and specificity, providing reference for the diagnosis of NS.
3.Application of 3D slicer plus Sina software for performing hematoma puncture and drainage after local anesthesia in elderly patients with intracerebral hemorrhage
Lisha DENG ; Xiaolin HOU ; Dongdong YANG ; Dingjun LI ; Chengxun LI ; Lin ZENG ; Yuan YAO
Chinese Journal of Geriatrics 2022;41(3):276-280
Objective:To explore the effect of minimally invasive hematoma puncture and drainage in the treatment of elderly patients with cerebral hemorrhage by using 3D slicer and Sina software to conduct 3D reconstruction and preoperative localization of intracerebral hematoma.Methods:A total of 74 elderly patients with a first-onset intracerebral hematoma aged ≥75 years, having surgical indications and stable vital signs were grouped into 3D slicer plus Sina software localization group(as group A, n=40)or CT localization group(as group B, n=34). Based on the localization, hematoma puncture and drainage were performed after local anesthesia.Preoperative preparation time, hematoma location, puncture success rate, postoperative hematoma clearance rate, postoperative re-bleeding rate and GCS score were statistically analyzed.Glasgow coma scale(GCS)scores were used in predicting the mortality.Results:The preoperative preparation time was significantly shorter in group A than in group B[(5.5±3.4)min vs.(8.5±2.7)min, t=3.337, P=0.001]. The success rate of hematoma puncture and drainage(90.0% and 70.6%, χ2=4.51, P=0.034)and postoperative hematoma clearance rate[(87.5±3.4)% and(80.3±2.7)%, t=10.10, P=0.000]were higher in group A than in group B. There were no significant differences in operative time, the accuracy of hematoma localization, re-bleeding rate and GCS score between the two groups( P>0.05). Conclusions:3D slicer plus Sina software can precisely locate the intracerebral hematoma, and minimally invasive hematoma puncture and drainage of intracerebral hematoma under local anesthesia were safe and effective in the treatment of elderly patients with intracerebral hemorrhage.
4.Current progress of computational modeling for guiding clinical atrial fibrillation ablation.
Zhenghong WU ; Yunlong LIU ; Lv TONG ; Diandian DONG ; Dongdong DENG ; Ling XIA
Journal of Zhejiang University. Science. B 2021;22(10):805-817
Atrial fibrillation (AF) is one of the most common arrhythmias, associated with high morbidity, mortality, and healthcare costs, and it places a significant burden on both individuals and society. Anti-arrhythmic drugs are the most commonly used strategy for treating AF. However, drug therapy faces challenges because of its limited efficacy and potential side effects. Catheter ablation is widely used as an alternative treatment for AF. Nevertheless, because the mechanism of AF is not fully understood, the recurrence rate after ablation remains high. In addition, the outcomes of ablation can vary significantly between medical institutions and patients, especially for persistent AF. Therefore, the issue of which ablation strategy is optimal is still far from settled. Computational modeling has the advantages of repeatable operation, low cost, freedom from risk, and complete control, and is a useful tool for not only predicting the results of different ablation strategies on the same model but also finding optimal personalized ablation targets for clinical reference and even guidance. This review summarizes three-dimensional computational modeling simulations of catheter ablation for AF, from the early-stage attempts such as Maze III or circumferential pulmonary vein isolation to the latest advances based on personalized substrate-guided ablation. Finally, we summarize current developments and challenges and provide our perspectives and suggestions for future directions.
5.The application of overlay reconstruction technique of angiography in surgical planning of scalp arteriovenous fistulas
Chungang DAI ; Xiaoming XIE ; Zhe DENG ; Ailin CHEN ; Dongdong CAO ; Tao WU ; Yao WU ; Qing ZHU
Chinese Journal of Plastic Surgery 2021;37(5):508-513
Objective:To explore the value and technique details of the overlay reconstruction technique of angiography in surgical planning of scalp arteriovenous fistulas.Methods:The clinical data of patients admitted from February 2014 to April 2020 in the Neurosurgical Department of Second Affiliated Hospital of Soochow University with scalp arteriovenous fistulas were analyzed retrospectively. Preoperative angiography was carried out in all patients for diagnosis, and the angiographical data was obtained without injection of the contrast agent by the mode of XperCT Cereb. Fast HD followed by three-dimension rotation angiography (3DRA) with the contrast agent. The overlay reconstruction was achieved for surgical planning to demonstrate feeding arteries and drainage veins surrounding the fistula. Surgeries were conducted by resection or devascularization of the lesion. All patients were followed up in the out-patient clinic to assess the healing and to detect the symptomatic recurrence and scalp necrosis. The pathological changes of the lesion were observed by HE staining.Results:Five patients were enrolled in this study, including three males and two females aged from 10 to 60 years old (average 34.2-year-old). Pulsatile mass of local scalp was presented in all patients, one with a thin scalp. Five patients suffered from five scalp arteriovenous fistulas, including three on the right side and two on the left. Feeding arteries mainly originated from the superficial temporal artery were confirmed in four cases, and the posterior auricular artery in one case. Single venous drainage was noted in two cases, as well as multiple drainage veins in three cases. Three lesions were supplied by unilateral feeding arteries, while bilateral feeding arteries supplied the rest lesions. Two fistulas were treated by resection, two were treated by devascularization, and one was treated by resection with skin grafting. One lesion was fed by a single artery, three lesions were fed by two arteries, and one lesion was fed by three arteries. Three lesions were fed by unilateral arteries, and two lesions were fed by bilateral arteries. Single fistula was detected in one lesion and multiple fistulas in four lesions. Single drainage was confirmed in two lesions, doubled drainages in two lesions, and tripledrainages in one lesion. All patients experienced surgical treatment in one stage.Two patients underwent complete resection of the lesion, two with complete devascularization, and one with autologous thigh skin grafting after resection. Postoperative pathological examination demonstrated dilated and congested vascular lumen, which was consistent with arteriovenous fistula. All patients healed well after surgery. With13-87 months follow-up, no recurrence and necrosis were noted. Two were reexamined by cerebral angiography, which showed no recurrence.Conclusions:Digital subtraction angiography facilitates the diagnosis of scalp arteriovenous fistula accurately and effectively. The overlay reconstruction technique of angiography is crucial for precise localization of fistula shunt and the surrounding feeders and drainages, which is helpful for surgical planning.
6.The application of overlay reconstruction technique of angiography in surgical planning of scalp arteriovenous fistulas
Chungang DAI ; Xiaoming XIE ; Zhe DENG ; Ailin CHEN ; Dongdong CAO ; Tao WU ; Yao WU ; Qing ZHU
Chinese Journal of Plastic Surgery 2021;37(5):508-513
Objective:To explore the value and technique details of the overlay reconstruction technique of angiography in surgical planning of scalp arteriovenous fistulas.Methods:The clinical data of patients admitted from February 2014 to April 2020 in the Neurosurgical Department of Second Affiliated Hospital of Soochow University with scalp arteriovenous fistulas were analyzed retrospectively. Preoperative angiography was carried out in all patients for diagnosis, and the angiographical data was obtained without injection of the contrast agent by the mode of XperCT Cereb. Fast HD followed by three-dimension rotation angiography (3DRA) with the contrast agent. The overlay reconstruction was achieved for surgical planning to demonstrate feeding arteries and drainage veins surrounding the fistula. Surgeries were conducted by resection or devascularization of the lesion. All patients were followed up in the out-patient clinic to assess the healing and to detect the symptomatic recurrence and scalp necrosis. The pathological changes of the lesion were observed by HE staining.Results:Five patients were enrolled in this study, including three males and two females aged from 10 to 60 years old (average 34.2-year-old). Pulsatile mass of local scalp was presented in all patients, one with a thin scalp. Five patients suffered from five scalp arteriovenous fistulas, including three on the right side and two on the left. Feeding arteries mainly originated from the superficial temporal artery were confirmed in four cases, and the posterior auricular artery in one case. Single venous drainage was noted in two cases, as well as multiple drainage veins in three cases. Three lesions were supplied by unilateral feeding arteries, while bilateral feeding arteries supplied the rest lesions. Two fistulas were treated by resection, two were treated by devascularization, and one was treated by resection with skin grafting. One lesion was fed by a single artery, three lesions were fed by two arteries, and one lesion was fed by three arteries. Three lesions were fed by unilateral arteries, and two lesions were fed by bilateral arteries. Single fistula was detected in one lesion and multiple fistulas in four lesions. Single drainage was confirmed in two lesions, doubled drainages in two lesions, and tripledrainages in one lesion. All patients experienced surgical treatment in one stage.Two patients underwent complete resection of the lesion, two with complete devascularization, and one with autologous thigh skin grafting after resection. Postoperative pathological examination demonstrated dilated and congested vascular lumen, which was consistent with arteriovenous fistula. All patients healed well after surgery. With13-87 months follow-up, no recurrence and necrosis were noted. Two were reexamined by cerebral angiography, which showed no recurrence.Conclusions:Digital subtraction angiography facilitates the diagnosis of scalp arteriovenous fistula accurately and effectively. The overlay reconstruction technique of angiography is crucial for precise localization of fistula shunt and the surrounding feeders and drainages, which is helpful for surgical planning.
7.Clinical value of mean platelet volume/platelet count ratio in predicting short-term prognosis of elderly patients with acute exacerbation of chronic obstructive pulmonary disease
Hui ZHANG ; Dongdong WU ; Dongbo MA ; Xiang DENG ; Lijing LI ; Jing WANG
Chinese Journal of Geriatrics 2020;39(6):627-631
Objective:To explore the clinical value of mean platelet volume/platelet count ratio(MPV/PLT)in predicting short-term prognosis of elderly patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods:A total of 226 elderly patients with AECOPD admitted to our hospital from January 2017 to January 2019 were retrospectively enrolled as research subjects.All cases were divided into the survival group(n=175)and the death group(n=51), based on prognosis 28-day after admission.General data and laboratory test results were compared between the two groups.The relevant factors for death were analyzed by the Logistic regression equation.The receiver operating characteristic(ROC)curve was used to evaluate the prognostic value of MPV/PLT, and the Kaplan-Meier survival curve was drawn according to the cut-off.Methods:Compared with the survival group, Acute Physiology and Chronic Health Status Evaluation(APACHEⅡ)score, levels of procalcitonin(PCT), high-sensitivity C-reactive protein(hs-CRP), creatinine, neutrophil count(NEU), lymphocyte count(LYM)and MPV were elevated, and levels of albumin and PLT decreased in the death group( P<0.05). Hospital stay lengths and costs were higher in the death group than in the survival group( P<0.05). The level of MPV/PLT was higher in the death group than in the survival group(0.065±0.016 vs.0.054±0.013, t=5.036, P<0.01). Multivariate Logistic regression showed that MPV/PLT was an independent risk factor for recent death( OR=2.331, 95% CI: 1.772-8.224, P<0.01). ROC curve analysis showed that the area under the curve(AUC)of MPV/PLT was 0.829, the sensitivity was 83.41%, the specificity was 82.80%, and the cut-off was 0.061.Optimal cut-off value analysis showed that APACHEⅡ score, PCT and hs-CRP levels and mortality were higher in patients with MPV/PLT≥0.061 than in patients with MPV/PLT<0.061( P<0.05). The Kaplan Meier survival curve showed that the cumulative survival rate was lower in those with MPV/PLT≥0.061 than in those with MPV/PLT<0.061( Log- rank=6.323, P<0.05). Conclusions:The increase of MPV/PLT may be an independent risk factor for recent death in elderly patients with AECOPD and has good clinical value in predicting poor prognosis.
8.Comparison of intracranial venous pressures in patients with idiopathic intracranial hypertension under awake setting or general anesthesia
Xinbin GUO ; Sen WEI ; Xiaozhen SUN ; Xin DENG ; Feng FAN ; Dongdong LI ; Zhen CHEN ; Sheng GUAN
Chinese Journal of Neuromedicine 2020;19(9):958-960
Objective:To investigate the changes of mean venous sinus pressure (MVP) and trans-stenosis pressure gradient in patients with idiopathic intracranial hypertension (IIH) under awake setting and general anesthesia.Methods:Thirty-eight patients with IIH accepted venous sinus stent implantation in our hospital from January 2010 to January 2020 were chosen in our study; their clinical data were analyzed retrospectively. The manometry results of these 38 patients were recorded under awake setting and general anesthesia before stenting; MVP and trans-stenosis pressure gradient were obtained and compared.Results:MVP in the superior sagittal sinus, torcular, transverse sinus and sigmoid sinus showed no significant difference between patients under awake setting and general anesthesia ( P>0.05). Mean trans-stenosis pressure gradient in patients under awake setting ([22.784±7.606] mmHg) was significantly higher as compared with that in patients under general anesthesia ([18.388±8.992] mmHg, P<0.05). Conclusion:Mean trans-stenosis pressure gradient in patients under awake setting is higher as compared with that in patients under general anesthesia, and selection for venous sinus stent implantation should be decided by trans-stenosis pressure gradient in patients under awake setting.
9.Chinese Society of Allergy Guidelines for Diagnosis and Treatment of Allergic Rhinitis.
Lei CHENG ; Jianjun CHEN ; Qingling FU ; Shaoheng HE ; Huabin LI ; Zheng LIU ; Guolin TAN ; Zezhang TAO ; Dehui WANG ; Weiping WEN ; Rui XU ; Yu XU ; Qintai YANG ; Chonghua ZHANG ; Gehua ZHANG ; Ruxin ZHANG ; Yuan ZHANG ; Bing ZHOU ; Dongdong ZHU ; Luquan CHEN ; Xinyan CUI ; Yuqin DENG ; Zhiqiang GUO ; Zhenxiao HUANG ; Zizhen HUANG ; Houyong LI ; Jingyun LI ; Wenting LI ; Yanqing LI ; Lin XI ; Hongfei LOU ; Meiping LU ; Yuhui OUYANG ; Wendan SHI ; Xiaoyao TAO ; Huiqin TIAN ; Chengshuo WANG ; Min WANG ; Nan WANG ; Xiangdong WANG ; Hui XIE ; Shaoqing YU ; Renwu ZHAO ; Ming ZHENG ; Han ZHOU ; Luping ZHU ; Luo ZHANG
Allergy, Asthma & Immunology Research 2018;10(4):300-353
Allergic rhinitis (AR) is a global health problem that causes major illnesses and disabilities worldwide. Epidemiologic studies have demonstrated that the prevalence of AR has increased progressively over the last few decades in more developed countries and currently affects up to 40% of the population worldwide. Likewise, a rising trend of AR has also been observed over the last 2–3 decades in developing countries including China, with the prevalence of AR varying widely in these countries. A survey of self-reported AR over a 6-year period in the general Chinese adult population reported that the standardized prevalence of adult AR increased from 11.1% in 2005 to 17.6% in 2011. An increasing number of original articles and imporclinical trials on the epidemiology, pathophysiologic mechanisms, diagnosis, management and comorbidities of AR in Chinese subjects have been published in international peer-reviewed journals over the past 2 decades, and substantially added to our understanding of this disease as a global problem. Although guidelines for the diagnosis and treatment of AR in Chinese subjects have also been published, they have not been translated into English and therefore not generally accessible for reference to non-Chinese speaking international medical communities. Moreover, methods for the diagnosis and treatment of AR in China have not been standardized entirely and some patients are still treated according to regional preferences. Thus, the present guidelines have been developed by the Chinese Society of Allergy to be accessible to both national and international medical communities involved in the management of AR patients. These guidelines have been prepared in line with existing international guidelines to provide evidence-based recommendations for the diagnosis and management of AR in China.
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10.Establishment of cerebral venous sinus thrombosis model in rabbits by using ferric chloride combined with thrombin injection
Ying WEI ; Sheng GUAN ; Xinbin GUO ; Xin DENG ; Zibo WANG ; Dongdong LI ; Xiaoke LU ; Yanhua DONG
Journal of Interventional Radiology 2018;27(2):151-156
Objective To discuss the establishment of cerebral venous sinus thrombosis (CVST) model in rabbits by local application of ferric chloride at sinuses sagittalis superior (SSS) combined with thrombin injection, and to evaluate its feasibility and application value. Methods A total of 39 New Zealand white rabbits were randomly and equally divided into three groups with 13 rabbits in each group, local application of cotton piece saturated with saline at SSS for 10 minutes was performed for the rabbits of group A, SSS local application of cotton piece saturated with 40% ferric chloride for 10 minutes was adopted for the rabbits of group B, while SSS local application of cotton piece saturated with 40% ferric chloride for 5 minutes together with injection of thrombin was carried out for the rabbits of group C. Whole cerebral DSA was performed immediately after modeling to judge if there was formation of thrombosis. Two days after the modeling, every 3 rabbits from each group were sacrificed to make 2, 3, 5-chloride triphenyl tetrazole (TTC) staining. Seven days after the modeling, the remaining 10 rabbits of each group were examined with DSA, the vascular recanalization rates were calculated, and the histopathological examination was made. Results In group B and group C, SSS thrombosis with surrounding cerebral infarction, edema, inflammatory cell aggregation and other pathological changes were observed. The 7-day vascular recanalization rate in group C was strikingly lower than that in group B (10% vs 70%, P<0.05). Surrounding cortical vein thrombus and subcortex petechial hemorrhages were obviously seen in group C. Conclusion For the establishment of CVST model in rabbits, local application of ferric chloride at SSS together with thrombin injection is effective and feasible. The thrombus thus induced is quite stable, and its pathogenesis and pathophysiology are quite similar to clinical manifestations. Therefore, this method can be used for basic research and clinical trials of CVST.

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