1.Mechanism of Neochlorogenic Acid in Ameliorating Psoriatic Keratinocyte Proliferation and Inflammation by Targeting HSP90 to Modulate NF-κB/NLRP3 Signaling Pathway
Mengyao JIANG ; Xinwei ZHANG ; Bin YANG ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):89-98
ObjectiveTo investigate the target proteins directly bound by neochlorogenic acid (NA) and the molecular mechanisms that ameliorate the proliferation and inflammatory response of psoriatic keratinocytes. MethodsM5-induced HaCaT cells were used as a psoriatic keratinocyte proliferation and inflammatory cell model. The synthesized NA probe (NA-P) and NA prodrug were first evaluated for cell viability using a cell proliferation/cell counting kit-8(CCK-8). The potency of NA and NA-P was evaluated in the safe concentration range, and the effects of 0-100 μmol·L-1 NA and probe on M5-induced proliferation of HaCaT cells were detected using CCK-8. The effects of 20, 40, 80 μmol·L-1 NA and 80 μmol·L-1 NA-P on the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-23 (IL-23), and interleukin-17A (IL-17A) inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to measure the effects of NA on the mRNA expression of keratin 16 (K16) in HaCaT cells, S100 calcium-binding protein A9 (S100A9), S100 calcium-binding protein A7 (S100A7), IL-6, IL-17A, and chemokine 1 (CXCL1). In vitro fluorescence labeling and competition experiments using NA-P were performed, and target protein angling and analysis using pull-down experiments combined with liquid chromatography-mass spectrometry (Pull-down/LC-MS/MS) were conducted. Target validation was performed using pull-down experiments combined with protein immunoblotting (Pull down-WB), cellular heat transfer analysis combined with protein immunoblot (CETSA-WB) experiments, and molecular docking. Finally, Real-time PCR was utilized to detect the effects of 20, 40, 80 μmol·L-1 NA and 80 μmol·L-1 NA-P on the mRNA expression of IL-1β, nucleotide-binding oligomeric structural domain-like receptor protein 3 (NLRP3), apoptosis-associated speckled-like protein (ASC), and cysteine protease-1 (Caspase-1) in HaCaT cells. Protein immunoblot (Western blot) was used to detect the effects of phosphorylated p65 (p-p65), p65, phosphorylated human nuclear factor-κB inhibitory protein α (p-IκBα), human nuclear factor κB inhibitory protein α (IκBα), and heat shock protein 90 (HSP90) expression. ResultsIn the 200 μmol·L-1 safe concentration range, HaCaT cell proliferation, increased expression of TNF-α, IL-1β, IL-23, and IL-17A inflammatory factors, and increased mRNA expression of K16, S100A9, S100A7, IL-6, IL-17A, and CXCL1 were observed in the M5 group compared with the blank group. Cell proliferation in 5-100 μmol·L-1 NA and NA-P groups was inhibited, and the expression of TNF-α, IL-1β, IL-23, and IL-17A inflammatory factors was decreased in the NA-L, NA-M, NA-H, and NA-P-H groups. The mRNA expression of K16, S100A9, S100A7, IL-6, IL-17A, and CXCL1 was decreased (P<0.05). High-confidence targets were screened for HSP90 protein by Pull-down/LC-MS/MS using 200 μmol·L-1 NA competing with 100 μmol·L-1 NA-P. Compared with that in the blank group, the mRNA expression of NLRP3, IL-1β, ASC, and Caspase-1, as well as the expression of p-p65/p65, p-IκBα/IκBα, and HSP90 protein, were increased in HaCaT cells in the M5 group (P<0.05). Compared with that in the M5 group, the mRNA expression of NLRP3, IL-1β, ASC, and Caspase-1 of cells in the NA-L group, the NA-M group, the NA-H group, and the NA-P-H group was decreased (P<0.05). p-p65/p65 and p-IκBα/IκBα were decreased in the NA-M and NA-H groups (P<0.05), and there was no change in HSP90 protein. Pull down-WB showed that NA could directly target HSP90 protein, and NA binding to HSP90 protein enhanced its thermal stability. Molecular docking of NA with HSP90 family proteins HSP90AA1, HSP90B1, and HSP90AB1 all resulted in highly stable binding. ConclusionNA can inhibit the proliferation and inflammatory response of psoriatic keratinocytes by a mechanism that may be achieved by targeting HSP90 to modulate the NF-κB/NLRP3 signaling pathway.
2.Mechanism of Neochlorogenic Acid in Ameliorating Psoriatic Keratinocyte Proliferation and Inflammation by Targeting HSP90 to Modulate NF-κB/NLRP3 Signaling Pathway
Mengyao JIANG ; Xinwei ZHANG ; Bin YANG ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):89-98
ObjectiveTo investigate the target proteins directly bound by neochlorogenic acid (NA) and the molecular mechanisms that ameliorate the proliferation and inflammatory response of psoriatic keratinocytes. MethodsM5-induced HaCaT cells were used as a psoriatic keratinocyte proliferation and inflammatory cell model. The synthesized NA probe (NA-P) and NA prodrug were first evaluated for cell viability using a cell proliferation/cell counting kit-8(CCK-8). The potency of NA and NA-P was evaluated in the safe concentration range, and the effects of 0-100 μmol·L-1 NA and probe on M5-induced proliferation of HaCaT cells were detected using CCK-8. The effects of 20, 40, 80 μmol·L-1 NA and 80 μmol·L-1 NA-P on the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-23 (IL-23), and interleukin-17A (IL-17A) inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to measure the effects of NA on the mRNA expression of keratin 16 (K16) in HaCaT cells, S100 calcium-binding protein A9 (S100A9), S100 calcium-binding protein A7 (S100A7), IL-6, IL-17A, and chemokine 1 (CXCL1). In vitro fluorescence labeling and competition experiments using NA-P were performed, and target protein angling and analysis using pull-down experiments combined with liquid chromatography-mass spectrometry (Pull-down/LC-MS/MS) were conducted. Target validation was performed using pull-down experiments combined with protein immunoblotting (Pull down-WB), cellular heat transfer analysis combined with protein immunoblot (CETSA-WB) experiments, and molecular docking. Finally, Real-time PCR was utilized to detect the effects of 20, 40, 80 μmol·L-1 NA and 80 μmol·L-1 NA-P on the mRNA expression of IL-1β, nucleotide-binding oligomeric structural domain-like receptor protein 3 (NLRP3), apoptosis-associated speckled-like protein (ASC), and cysteine protease-1 (Caspase-1) in HaCaT cells. Protein immunoblot (Western blot) was used to detect the effects of phosphorylated p65 (p-p65), p65, phosphorylated human nuclear factor-κB inhibitory protein α (p-IκBα), human nuclear factor κB inhibitory protein α (IκBα), and heat shock protein 90 (HSP90) expression. ResultsIn the 200 μmol·L-1 safe concentration range, HaCaT cell proliferation, increased expression of TNF-α, IL-1β, IL-23, and IL-17A inflammatory factors, and increased mRNA expression of K16, S100A9, S100A7, IL-6, IL-17A, and CXCL1 were observed in the M5 group compared with the blank group. Cell proliferation in 5-100 μmol·L-1 NA and NA-P groups was inhibited, and the expression of TNF-α, IL-1β, IL-23, and IL-17A inflammatory factors was decreased in the NA-L, NA-M, NA-H, and NA-P-H groups. The mRNA expression of K16, S100A9, S100A7, IL-6, IL-17A, and CXCL1 was decreased (P<0.05). High-confidence targets were screened for HSP90 protein by Pull-down/LC-MS/MS using 200 μmol·L-1 NA competing with 100 μmol·L-1 NA-P. Compared with that in the blank group, the mRNA expression of NLRP3, IL-1β, ASC, and Caspase-1, as well as the expression of p-p65/p65, p-IκBα/IκBα, and HSP90 protein, were increased in HaCaT cells in the M5 group (P<0.05). Compared with that in the M5 group, the mRNA expression of NLRP3, IL-1β, ASC, and Caspase-1 of cells in the NA-L group, the NA-M group, the NA-H group, and the NA-P-H group was decreased (P<0.05). p-p65/p65 and p-IκBα/IκBα were decreased in the NA-M and NA-H groups (P<0.05), and there was no change in HSP90 protein. Pull down-WB showed that NA could directly target HSP90 protein, and NA binding to HSP90 protein enhanced its thermal stability. Molecular docking of NA with HSP90 family proteins HSP90AA1, HSP90B1, and HSP90AB1 all resulted in highly stable binding. ConclusionNA can inhibit the proliferation and inflammatory response of psoriatic keratinocytes by a mechanism that may be achieved by targeting HSP90 to modulate the NF-κB/NLRP3 signaling pathway.
3.Mechanism of Tibetan Medicine Sanwei Doukoutang to Improve Cognitive Dysfunction in 5×FAD Mice Based on Wnt/β-catenin Signaling Pathway
Shuran LI ; Yaxin WANG ; Jing SUN ; Lei BAO ; Zihan GENG ; Dan XIE ; Ronghua ZHAO ; Yanyan BAO ; Qiyue SUN ; Jingsheng ZHANG ; Xinwei WANG ; Xinying LI ; Xihe CUI ; Xiaowei YANG ; LIUXIAN ; Mengyao CUI ; Qingshan LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):54-60
ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang (SWDK) on cognitive dysfunction in mice suffering from Alzheimer's disease (AD) and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group, total ginsenoside group(0.04 g·kg-1), high-, medium-, and low-dose groups of SWDK (32.60, 16.30, 8.15 g·kg-1), with 10 mice in each group, and ten wild-type mice of the same age were used as the normal group, male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin (HE) staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin (SYP) and postsynaptic dense substance 95 (PSD95) in mice serum were detected by enzyme-linked immunosorbent assay (ELISA). The positive expression of brain-derived neurotrophic factor(BDNF) in the dentate gyrus (DG) region of mouse brain tissue was observed by immunohistochemistry (IHC). The protein levels of BDNF, Wnt family member 3A(Wnt3a), and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice, the model group of mice had significantly more complex swimming routes and lower swimming speed (P<0.01), significantly lower percentage of time spent in the target quadrant (P<0.01), and a significantly lower percentage of freezing time (P<0.05). The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95(P<0.01) in the serum of mice were reduced, and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice were obviously reduced (P<0.05, P<0.01). Compared with the model group, the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes, the high- and medium- dose SWDK groups significantly higher swimming speeds (P<0.01), significantly higher percentage of time spent in the target quadrant (P<0.01), obviously higher percentage of Freezing time (P<0.05), and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP (P<0.05, P<0.01), PSD95 (P<0.01), increased BDNF-positive cells in the DG region of brain tissue, and obviously elevated levels of BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice (P<0.05, P<0.01). ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice, and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway, which promotes BDNF expression and thereby enhances synaptic plasticity, allowing neuronal signaling to be restored.
4.Mechanism of Tibetan Medicine Sanwei Doukoutang to Improve Cognitive Dysfunction in 5×FAD Mice Based on Wnt/β-catenin Signaling Pathway
Shuran LI ; Yaxin WANG ; Jing SUN ; Lei BAO ; Zihan GENG ; Dan XIE ; Ronghua ZHAO ; Yanyan BAO ; Qiyue SUN ; Jingsheng ZHANG ; Xinwei WANG ; Xinying LI ; Xihe CUI ; Xiaowei YANG ; LIUXIAN ; Mengyao CUI ; Qingshan LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):54-60
ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang (SWDK) on cognitive dysfunction in mice suffering from Alzheimer's disease (AD) and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group, total ginsenoside group(0.04 g·kg-1), high-, medium-, and low-dose groups of SWDK (32.60, 16.30, 8.15 g·kg-1), with 10 mice in each group, and ten wild-type mice of the same age were used as the normal group, male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin (HE) staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin (SYP) and postsynaptic dense substance 95 (PSD95) in mice serum were detected by enzyme-linked immunosorbent assay (ELISA). The positive expression of brain-derived neurotrophic factor(BDNF) in the dentate gyrus (DG) region of mouse brain tissue was observed by immunohistochemistry (IHC). The protein levels of BDNF, Wnt family member 3A(Wnt3a), and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice, the model group of mice had significantly more complex swimming routes and lower swimming speed (P<0.01), significantly lower percentage of time spent in the target quadrant (P<0.01), and a significantly lower percentage of freezing time (P<0.05). The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95(P<0.01) in the serum of mice were reduced, and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice were obviously reduced (P<0.05, P<0.01). Compared with the model group, the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes, the high- and medium- dose SWDK groups significantly higher swimming speeds (P<0.01), significantly higher percentage of time spent in the target quadrant (P<0.01), obviously higher percentage of Freezing time (P<0.05), and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP (P<0.05, P<0.01), PSD95 (P<0.01), increased BDNF-positive cells in the DG region of brain tissue, and obviously elevated levels of BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice (P<0.05, P<0.01). ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice, and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway, which promotes BDNF expression and thereby enhances synaptic plasticity, allowing neuronal signaling to be restored.
5.Efficacy and safety of branched stent and fenestrated stent for thoracic aortic diseases in short landing zone
Pengli ZHOU ; Yang WANG ; Qinghui ZHANG ; Ling WANG ; Zhengyang WU ; Wenguang ZHANG ; Xinwei HAN
Chinese Journal of Radiology 2024;58(4):422-429
Objective:To compare the efficacy and safety of Castor single-branch stent and in vitro fenestration stent in treating thoracic aortic diseases with insufficient landing zone.Methods:The clinical data of patients with thoracic aortic diseases treated with Castor single-branch stent or in vitro fenestrated stent between December 2017 and June 2021 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. A total of 184 patients were included, 99 patients were treated with Castor branch stent, and 85 patients with in vitro fenestration stent. All patients′ general clinical data, surgical data, perioperative and follow-up clinical and imaging data, and postoperative complications were collected. The χ2 test was used to compare the incidence of complications between the two groups, and the Kaplan-Meier method was used to plot the survival rate without adverse events between the two groups. Results:Stent placement was successful in all patients, and the success rate of the technique was 100%. Other branches were reconstructed in 2 patients in the Castor group and double fenestrated stent were reconstructed in 12 patients in the fenestrated group. The mean operation time of the Castor group was significantly shorter than that of the fenestrated group, the number of patients who received local anesthesia was significantly lower than that of the fenestrated group, and the endoleak rate during follow-up was significantly lower than that of the fenestrated group ( P<0.05). There was no significant difference in the postoperative hospital stay, the incidence rate of perioperative complications, mortality, the incidence rate of neurological complications, new dissection or aneurysm rate, branch stent stenosis rate, second surgical intervention rate, and false lumen thrombosis between the two groups ( P>0.05). The adverse event-free survival rate of the Castor group was slightly higher than that of the fenestrated group, but its difference was not statistically significant ( P>0.05). Conclusion:Castor branch stent and in vitro fenestration stent have good short-term and mid-term efficacy in the treatment of aortic diseases with insufficient landing zone, which are safe and effective options for reconstruction of LSA and other branch arteries.
6.Duhuo Jisheng Decoction treats gouty arthritis by inhibiting NLRP3 inflammasome activation
Guangyi TAO ; Zhengzhen WANG ; Jiajun HUANG ; Diyou WU ; Xinwei WANG ; Shun YANG ; Bin YANG ; Junqing HUANG
Chinese Journal of Tissue Engineering Research 2024;28(32):5182-5189
BACKGROUND:The activation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome has been found to be an important factor in the pathogenesis of gouty arthritis,and the activation of NLPR3 inflammasome can be effectively inhibited by regulating the PTEN-induced kinas 1(PINK1)/Parkin signaling pathway. OBJECTIVE:To investigate the effect of Duhuo Jisheng Decoction on the PINK1/Parkin/NLRP3 signaling pathway. METHODS:(1)Animal experiment:Male Sprague-Dawley rats were randomly divided into control group,model group,positive control group(Qiushuixian tablets 0.3 mg/kg),and low-,medium-,and high-dose Duhuo Jisheng Decoction groups(6.9,13.8,and 27.6 g/kg,respectively).A rat gouty arthritis model was constructed by injecting monosodium urate crystal suspension into the right hind ankle joint cavity of rats in all the groups except for the control group.(2)Cell experiment:Human monocytes(THP-1)were divided into blank control group,model group,Duhuo Jisheng Decoction-containing serum group,and PINK1 siRNA+Duhuo Jisheng Decoction-containing serum group.The cells in each group except the blank control group were stimulated with sodium urate to establish an in vitro gouty arthritis model.(3)The swelling degree,joint circumference,gait score,joint inflammation index and degree of pathological grading in the ankle joints of rats were observed.Enzyme-linked immunosorbent assay was used to detect the levels of uric acid,C-reactive protein,NLRP3,and interleukin 1β.Immunoblotting assay was used to detect the levels of proteins related to the PINK1/Parkin/NLRP3 pathway.Tetramethyl azolidine blue assay was used to detect cell activity.Immunofluorescent double staining was performed to detect the level of mitophagy.Immunofluorescence was used to detect the expression of NLRP3 and interleukin 1β. RESULTS AND CONCLUSION:(1)Compared with the control group,rats in the model group showed elevated ankle swelling and ankle circumference at 6-48 hours(P<0.05),elevated gait scores and joint inflammation indexes at 24 and 48 hours(P<0.05),elevated serum uric acid and C-reactive protein levels,degree of pathological classification,expression of PINK1,Parkin,and NLRP3 proteins,and interleukin 1β level in synovial tissues(P<0.05).Compared with the model group,the protein expression levels of PINK1 and Parkin in all the Duhuo Jisheng Decoction groups were elevated,while the levels of the other indexes were decreased(P<0.05).(2)Compared with the model group,NLRP3 activity,interleukin 1β level and mitochondrial outer membrane translocator protein 20 protein level in the Duhuo Jisheng Decoction-containing serum group were decreased(P<0.05),while the proliferation inhibition rate,PINK1,Parkin and LC3B protein level were increased(P<0.05).Compared with the model group,the mitochondrial autophagy level of cells in the Duhuo Jisheng Decoction-containing serum group was elevated(P<0.05),while NLRP3 and interleukin 1β protein levels were decreased(P<0.05).(3)Compared with the Duhuo Jisheng Decoction-containing serum group,the mitochondrial autophagy level of cells in the PINK1 siRNA+Duhuo Jisheng Decoction-containing serum group was decreased(P<0.05),and the expression levels of NLRP3 and interleukin 1β were elevated(P<0.05).To conclude,Duhuo Jisheng Decoction inhibits the activation of NLRP3 inflammasome by regulating the PINK1/Parkin signaling pathway, thereby exerting a therapeutic effect on gouty arthritis.
7.Dihydroartemisinin promotes radiotherapy sensitivity of nasopharyngeal carcinoma CNE-2Z cells by activating chloride channels
Shiqing LIU ; Congran ZHOU ; Xinwei TANG ; Hanfen ZHOU ; XueKe LI ; Xi-Uying HOU ; Haifeng YANG ; Linyan ZHU
Chinese Journal of Pathophysiology 2024;40(2):255-264
AIM:To investigate the role of ClC-3 chloride channel in the promotion of radio sensitization of na-sopharyngeal carcinoma CNE-2Z cells by dihydroartemisinin(DHA).METHODS:MTT was used to detect the inhibito-ry effect of DHA on the viability of CNE-2Z cells and normal nasopharyngeal epithelial NP69-SV40T cells,the radio sensi-tization effect of DHA on CNE-2Z cells was detected by cloning assay,the expression of ClC-3 protein was detected by Western blot,the expression of ClC-3 protein was down-regulated by siRNA technology,and the chlorine current of cells was recorded by whole cell patch-clamp technology.RESULTS:(1)Compared with NP69-SV40T cells,DHA selective-ly inhibited the proliferation of CNE-2Z cells,with IC10 values of(13.020±4.831)μmol/L and(5.244±1.050)μmol/L,respectively(P<0.01).(2)The results of clonal formation experiments showed that DHA had a radio sensitizing effect on CNE-2Z cells,with a radio sensitization ratio of 1.9.(3)DHA could activate the chlorine channel of CNE-2Z cells and produce an outward chlorine current,but had no effect on the chlorine channel of NP69-SV40T cells.(4)DHA promoted the expression of ClC-3 chloric channel protein in CNE-2Z cells(P<0.01).(5)Chlorine channel blocker NPPB could in-hibit the radio sensitizing effect of DHA on CNE-2Z cells by 1.84 times,and also inhibited the chlorine current activated by DHA.(6)the down-regulation of CNE-2Z ClC-3 protein could inhibit the radio sensitization effect of DHA on CNE-2Z cells by 4.19 times,and the activation of chlorine current by DHA on CNE-2Z cells was no longer produced.CONCLU-SION:DHA has a radio sensitizing effect on nasopharyngeal carcinoma CNE-2Z cells,which is likely to be related to the activation of ClC-3 chloride channel.
8.Imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses and efficacy and safety of intravascular interventional therapy in them
Tengfei LI ; Qi TIAN ; Shuailong SHI ; Jie YANG ; Ye WANG ; Zhen CHEN ; Yuncai RAN ; Baohong WEN ; Dong GUO ; Shaofeng SHUI ; Xinwei HAN ; Xiao LI ; Ji MA
Chinese Journal of Neuromedicine 2024;23(1):42-47
Objective:To summarize the imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses, and evaluate the efficacy and safety of intravascular interventional therapy in them.Methods:Thirty-seven patients with severe unilateral transverse sinus and sigmoid sinus thromboses clinically mainly manifested as intracranial hypertension and accepted endovascular intervention in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2012 to September 2022 were chosen; their clinical data were retrospectively analyzed and imaging features were summarized. Short-term efficacy was evaluated according to blood flow restoration degrees and pressure gradient reduction in the occlusive sinus and modified neurological symptoms before and after endovascular intervention. Hospitalized complications were observed; safety and long-term efficacy were evaluated according to postoperative clinical follow-up and imaging results 6-12 months after endovascular intervention.Results:(1) Preoperative brain MRI and (or) CT showed different degrees of swelling of the brain tissues, with the affected side as the target; mixed signals/density shadow could be seen in the blocked transverse sinus and sigmoid sinus; venous cerebral infarction or post-infarction cerebral hemorrhage could be combined in some patients. MRV, CTV and DSA showed poor or completely occluded transverse sinus and sigmoid sinus while normal in the contralateral side; obvious thrombus filling-defect was observed in the occluded venous sinus after mechanical thrombolysis. (2) Occlusive sinus blood flow was restored in all patients after endovascular intervention, and pressure gradient of the occlusive segment decreased from (16.6±3.3) mmHg before to (2.8±0.8) mmHg after endovascular intervention. Before discharge, clinical symptoms of all patients were significantly improved (modified Rankin scale [mRS] scores of 0 in 30 patients, 1 in 5 patients, 2 in 1 patient and 3 in 1 patient), and 2 patients had unilateral limb movement disorder (muscle strength grading III and IV, respectively). All patients received clinical follow-up for (9.6±3.0) months. At the last follow-up, neurological function obviously improved compared with that before endovascular intervention, without new neurosystem-related symptoms (mRS scores of 0 in 30 patients, 1 in 6, and 2 in 1 patient). In 34 patients received MRV or DSA follow-up, 28 had complete recanalization of occlusive sinus and 6 had partial recanalization, without obvious stenosis or recurrent occlusion.Conclusions:Severe unilateral transverse sinus and sigmoid sinus thrombosis can cause local intracranial venous blood stasis, and then cause "increased regional venous sinus pressure", which is manifested as unilateral brain tissue swelling and even venous cerebral infarction or post-infarction cerebral hemorrhage. Early diagnosis and endovascular intervention can obviously improve the prognosis of these patients, enjoying good safety.
9.OCT and IVUS evaluating stent apposition and endothelialization after FD implantation in aneurysm animal models
Ji MA ; Shuhai LONG ; Jie YANG ; Zhen LI ; Haiqiang SANG ; Yi TANG ; Yuncai RAN ; Yong ZHANG ; Baohong WEN ; Shanshan XIE ; Ke CHEN ; Enjie LIU ; Xinwei HAN ; Tengfei LI
Chinese Journal of Neuromedicine 2024;23(3):256-262
Objective:To investigate the application value of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in evaluating flow diverter (FD) apposition and endothelialization in aneurysm animal models, and analyze the effect of incomplete stent apposition (ISA) on aneurysm lumen healing and stent endothelialization.Methods:Lateral common carotid artery aneurysm models in swines were established by surgical method and then FD was implanted. Immediately after surgery, OCT and IVUS were used to evaluate the locations and degrees of ISA, and difference between these 2 methods in evaluating FD apposition was compared. DSA was performed at 12 weeks after surgery to evaluate the aneurysm occlusion (Kamran grading) and stent patency. OCT and IVUS were used again to observe the stent endothelial situation; by comparing with histopathologic results, effect of ISA on aneurysm healing and stent endothelialization was analyzed.Results:Lateral common carotid artery aneurysm models in 6 swines were established, and 6 Tubridge FDs were successfully implanted. Compared with IVUS (3 stents, 4 locus), OCT could detect more ISA (6 stents, 14 locus); and the vascular diameter change area (7 locus), aneurysm neck area (4 locus) and the head and tail of FD (3 locus) were the main sites of FD malapposition; average distance between stent wire and vessel wall was (560.14±101.48) μm. At 12 weeks after surgery, DSA showed that 1 patient had a little residual contrast agent at the aneurysm neck (Kamran grading 3), and the remaining 5 had complete aneurysm occlusion (Kamran grading 4). One FD had moderate lumen stenosis, and the other 5 FDs had lumen patency. OCT indicated mostly disappeared acute ISA; ISA proportion decreased to 21.4 % (3/14), including 2 in the aneurysm neck and 1 in the partial stent. Histopathological results showed bare stent woven silk, without obvious endothelial coverage; in one FD with luminal stenosis, intimal hyperplasia was mainly composed of vascular smooth muscle cells.Conclusion:In carotid artery aneurysm model with FD implantation, OCT can detect more ISA than IVUS; most acute ISA have good outcome at 12 th week of follow-up, while severe ISA can cause delayed FD endothelialization and delayed aneurysm occlusion.
10.The association between body mass index and in-hospital major adverse cardiovascular and cerebral events in patients with acute coronary syndrome
Qing ZHOU ; Dan ZHU ; Yiting WANG ; Wenyue DONG ; Jie YANG ; Jun WEN ; Jun LIU ; Na YANG ; Dong ZHAO ; Xinwei HUA ; Yida TANG
Chinese Journal of Cardiology 2024;52(1):42-48
Objective:To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS).Methods:This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m 2), normal weight (BMI between 18.5 and 24.9 kg/m 2), overweight (BMI between 25.0 and 29.9 kg/m 2), and obese (BMI≥30.0 kg/m 2). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results:A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively ( P<0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group ( OR=1.30, 95% CI 1.13-1.49, P<0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P>0.05). Conclusion:ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.

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