Although in the treatment of extracranial vascular malformations the absolute ethanol used as an embolization agent has several advantages(such as low cost,reliable efficacy,no impact on subsequent treatments,etc.)and has already achieved significant progress in clinical practice,it is still regarded as a highly-selective liquid embolization agent in the sclerotherapy or embolization treatment of brain arteriovenous malformation(bAVM).At present,the indications of sclerotherapy and embolization therapy by using absolute ethanol include small AVM(＜3 cm)located at brain cortex or at non-eloguent area,and relatively low-flow AVM,in such case,the absolute ethanol acts as an effective supplement to other liquid embolization agents.Further studies are needed so as to improve the radiographic visualization and viscosity of absolute ethanol,to make the injection process more controlled,and to alleviate the edema caused by neurotoxicity and inflammation.

Due to their unique peroxide bridge structure,artemisinin and its derivatives have demonstrated the remarkable efficacy in treating severe malaria and exhibited the potent anticancer properties.These compounds interfere with the cancer cell growth through the multiple mechanisms,including the inhibition of cell proliferation,induction of various forms of cell death,cell cycle arrest,suppression of angiogenesis and modulation of the tumor microenvironment.Clinical trials have confirmed the significant anticancer activity of artemisinin-based compounds.This paper summarizes the recent advances and findings regarding the mechanisms of action of artemisinin and its derivatives as the potential anticancer agents,providing the valuable insights for future researches on the anticancer mechanisms of these compounds.

Objective To investigate the value of pulse oxygen perfusion index(PI)and blood lactic acid(BLA)concentration in early prediction of retinopathy of prematurity(ROP).Methods A retrospective case-control study was conducted on 128 preterm infants who met the inclusion criteria and were admitted to the neonatal intensive care unit of our hospital from September 2018 to December 2022.Among them,46 patients with ROP were in the ROP group,and 82 pa-tients without ROP were in the non-ROP group.Basic data of these preterm infants were recorded after admission.PI val-ues were continuously monitored with the Masimo Radical-7(USA)SpO2 blood oxygen saturation detector,and BLA con-centrations were detected with the ABL90FLEX blood gas analyzer.The receiver operating characteristic(ROC)curve and area under curve(AUC)were used to evaluate the value of PI and BLA concentration in early prediction of ROP.Results There were no significant differences in gestational age,birth weight,sex,and delivery mode between the two groups(all P＞0.05).The PI values after birth were significantly different between the two groups(Fgroup=15.393,Pgroup＜0.001).The PI values of preterm infants in the ROP group decreased significantly at 1 h,12 h and 24 h after birth and slightly at 48 h to 96 h after birth compared with the non-ROP group.The PI values of preterm infants in the two groups sta-bilized at 96 h after birth.The PI values of preterm infants in the ROP group were lower than those in the non-ROP group at all time points within 96 h after birth(all P＜0.05).The PI values showed interaction effects between the two groups at different time points(Finteraction=5.061,Pinteraction＜0.001).There was a significant difference in BLA concentration between the two groups after birth(Fgroup=91.158,Pgroup＜0.001).In the ROP group,the BLA concentration increased significantly at 1 h after birth and slightly at 12 h and 24 h after birth compared with the non-ROP group.The BLA concentration in the ROP group was higher than that in the non-ROP group at all time points after birth(all P＜0.05).The BLA concentration showed no interaction effects between the two groups at different time points(Finteraction=0.567,Pinteraction＞0.05).The AUC of PI values at 1 h,12 h and 24 h after birth and BLA concentration at 1 h after birth for predicting ROP was 0.77,0.82,0.83,and 0.82,respectively.The AUC of combined PI values at 1 h,12 h and 24 h after birth and BLA concentration at 1 h after birth for predicting ROP was 0.94,higher than the predictive value of a single indicator.Conclusion PI and BLA concentration have good clinical value for early prediction of ROP.

Objective:To investigate the protective effect and mechanism of silymarin on bronchiolitis caused by respiratory syncytial virus (RSV) in mice.Methods:A mouse model of bronchiolitis was established by intranasal instillation of RSV. After successful modeling, the mice were randomly divided into a model group, a positive control group (ribavirin, 10 mg/kg), a low-dose silymarin group (25 mg/kg), a medium-dose silymarin group (50 mg/kg), and a high-dose silymarin group (100 mg/kg). In addition, a control group was established, with 12 mice in each group. The pulmonary index and RSV virus load were determined in each group of mice. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the lungs. The levels of interleukin-4 (IL-4), interferon-γ (IFN-γ), transforming growth factor-β (TGF-β), IL-17, and IL-10 in bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect the proportion of helper T cells 17 (Th17) and regulatory T cells (Treg) in peripheral blood. Western blot was used to detect the expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor κB subunit p65 (NF-κB p65), and phosphorylated nuclear protein p-NF-κB p65 in lung tissue.Results:Compared with the model group, the pulmonary injury and inflammatory response were significantly improved in the medium-and high-dose silymarin groups. The pulmonary indexes were (1.27±0.17)% and (0.94±0.10)%, respectively, and the RSV virus loads were (2.65±0.19) and (2.13±0.14), respectively, which were significantly lower than those in the model group (all P<0.05). The proportion of Th17 cells in peripheral blood was (4.47±0.19)% and (3.52±0.13)%, respectively, which was significantly lower than that in the model group (all P<0.05), while the proportion of Treg cells in peripheral blood was (0.88±0.08)% and (1.33±0.12)%, respectively, which was significantly higher than that in the model group (all P<0.05). The expression levels of IL-4 and IL-17 in BALF and the protein expression levels of TLR4/NF-κB signaling pathway related proteins in lung tissue were significantly lower than those in the model group (all P<0.05), while the expression levels of IFN-γ, TGF-β, and IL-10 in BALF were significantly higher than those in the model group (all P<0.05). Conclusions:Silymarin can regulate immune function and inhibit inflammatory response, thereby improving airway inflammation in bronchiolitis mice. The mechanism may be related to inhibit activation of TLR4/NF-κB signaling pathway.

Objective:To evaluate the safety and efficacy of endovascular interventional treatment of the intracranial vertebrobasilar trunk large aneurysms (VBTLAs) compared with conservative treatment.Methods:This is a prospective multi-center cohort study. From October 2012 to October 2018, a total of 69 patients with intracranial vertebrobasilar trunk large aneurysm (diameter>10 mm) from Henan Province People's Hospital and People's Liberation Army Rocket Medical Center were included in this study. Patients themselves chose either endovascular interventional therapy (interventional group) or conservative treatment (conservative group) after discussion with their doctors. The χ 2 test was used to compare the incidence of deaths, stroke, and all other serious adverse events including other site bleeding, myocardial infarction and others between the two groups. Results:A total of 69 patients were enrolled, of whom 51 patients were enrolled in interventional group, 18 patients underwent endovascular reconstructive therapy, 11 patients underwent deconstructive therapy, and 4 patients underwent conjunction interventional treatments. Eighteen patients were enrolled in conservative group, of whom 11 cases received simple risk factor control, 7 cases received antiplatelet and risk factors control. The proportions of hypertensive patients 94.4% (17/18) and giant aneurysms 50.0% (9/18) in the conservative group were higher than those in the surgery group 64.7% (33/51, χ 2=4.500, P=0.034), 19.6% (10/51, χ 2=4.730, P= 0.030).The incidence of all serious adverse events associated with protocol was 15.7% (8/51) in the interventional group and 44.4% (8/18) in the conservative group [risk ratio (RR) =0.353, 95% confidence intervals (CI): 0.156-0.801], and the difference was significant (χ 2=4.668, P=0.031). The incidence of fatal events associated with protocol was 2.0% (1/51) in the interventional group and 38.9% (7/18) in the conservative group (RR=0.050, 95%CI: 0.007-0.382), and the difference was significant (χ 2=14.281, P<0.001). The incidence of hemorrhage events associated with protocol was 2.0% (1/51) in the interventional group and 22.2% (4/18) in the conservative group (RR=0.088, 95%CI: 0.011-0.738), and the difference was significant (χ 2 =5.391, P=0.020). Follow-up imaging showed that the occlusion rate of aneurysms in 44 patients in the interventional group was 56.8% (25/44) after a median follow-up of 6 months. Imaging follow-up was obtained in 9 patients, whose occlusion rate of aneurysms was 0 and the median follow-up time was 12 months, in the conservative group. The difference was significant(χ 2 =7.534, P=0.006). Conclusion:Compared with conservative treatment, endovascular intervention of the intracranial VBTLAs has lower incidences of serious adverse events and death events.

Objective:To investigate the feasibility of absolute ethanol in the treatment of brain arteriovenous malformation (bAVM).Methods:The clinical data of 25 patients with bAVM treated with absolute ethanol in the specialty of intracranial vascular malformations in Henan Provincial People′s Hospital from September 2018 to May 2019 were retrospectively analyzed. There were 14 males and 11 females, aged 7-62 years, with a median age of 26 years. Among the 25 patients, 18 cases had ruptured bAVM, 7 cases had unruptured bAVM. Spezler-Martin grade<Ⅲ were found in 14 cases, Ⅲ grade in 7 cases, and >Ⅲ grade in 4 cases. The clinical effect and perioperative complications were observed.Results:Among 25 patients, the overall technical success rate was 96.0% (24/25), one of which the target lesion with anhydrous ethanol could not be ablated. The overall complication rate was 28.0% (7/25) with no death. All complications were ischemic, and the incidence of severe complications was 12.0% (3/25). Twenty-five patients were followed up 3 months after the operation, 4 of which had mild complications, 2 recovered completely and 2 made reasonable recovery. In the 3 patients with severe complications, 2 patients made reasonable recovery and 1 patient had significant improvement. The modified rankin scale (MRS) score of all patients with complications was ≤2, and the remaining 18 patients had no new onset clinical symptoms. Thirteen patients were followed up by DSA and MRI. DSA showed no recurrence in the lesions ablated by absolute ethanol. In 2 patients with partial residual malformation after operation, the residual deformities disappeared completely at the time of reexamination. MRI showed that brain edema disappeared in all patients.Conclusions:The ablation of absolute ethanol in bAVM has a high operation success rate, definite clinical effect and low recurrence rate of postoperative bAVM. It can be used as an exploratory treatment.

Objective: To investigate the aggravation of pancreatic tissue injury in rats with acute hypertriglyceridemic pancreatitis and the possible role of NADPH oxidase (NOX). Methods: Thirty SPF rats were randomly (random number)divided into five groups: N group, H group, NLAP group, HLAP group and HAPO group. AMY, TG, TC and FFA levels were detected. The pathological changes of pancreas were observed under light microscope and the ultrastructural changes of pancreatic acinar cells were observed by TEM. Serum levels of MDA, SOD, IL-1β, TNF-α and LDH were detected. The expression of NOX4, p-Akt and p-GSK3β in pancreas was detected by immunofluorescence, and the expression of NF-κB and TNF-α in pancreas was detected by immunohistochemistry. Results: Intraperitoneal injection of P-407 could significantly increase the levels of serum TG, TC and FFA in rats. After acute pancreatitis induced by L-Arg, the levels of serum AMY in the NLAP and HLAP groups were significantly increased, while Apocynin could significantly decrease the level of serum AMY. Compared with the NLAP group, the pathological injury of pancreatic tissue in the HLAP group was more serious, the level of inflammatory mediators was significantly increased, and the cell necrosis was more serious. After inhibiting NOX, the activation of Akt/GSK3β pathway was regulated and the pancreatic injury was improved. Conclusion In HTGP, NOX aggravates pancreatic injury by regulating the activation of Akt/GSK3 β pathway. Inhibition of NOX expression can play a protective role in pancreas injury of HTGP..

No abstract available.
Drug-Eluting Stents ; Stents ; Vertebral Artery ; Vertebrobasilar Insufficiency

Objective To investigate the role of Toll-like receptor 4 ( TLR4 ) and NOD-like receptor 3 (NLRP3)inflammasome in the liver injury of acute necrotizing pancreatitis (ANP) rat with obesity. Methods Twenty-four SD rats were randomly divided into normal group, ANP group, obesity group and obesity ANP group. The obesity rat model was established by continuously feeding high fat diet and the ANP model was induced by retrograde infusion of 5％ sodium taurocholate into the biliopancreatic duct. Rats were killed at 12 h after model establishment, and automatic biochemical immune analyzer were used for detecting serum AMY, LIP, ALT, AST, TG and TC. Pathological changes of pancreas and liver tissue samples were observed by miscroscopy and pathological score was recorded. The levels of MPO, CD68 , TLR4, NLRP3 and IL-1βin liver tissue were detected by immunofluorescence, and NF-κB and caspase-3 in liver tissue were detected by immunohistochemistry. Results The serum ALT and AST in obesity ANP group were significantly increased than those in ANP group (233. 00 ± 34. 44 U/L vs 102. 83 ± 8. 90 U/L,388. 00 ± 41. 60 U/L vs 282. 00 ± 21. 06 U/L);and liver pathologic score was also significantly higher than ANP group (6. 66 ± 1. 21 vs 3. 33 ± 1. 03);and CD68 + /TLR4 +, CD68 + /NLRP3 +, TLR4 + /NLRP3 +, MPO, NF-κB, IL-1β and caspase-3 level were all greatly higher in obesity ANP than those in ANP group, respectively (24. 16 ± 1. 47 vs 6. 66 ± 1. 21, 25. 00 ± 2. 60 vs 7. 00 ± 1. 41, 14. 16 ± 1. 47 vs 5. 50 ± 1. 04, 35. 33 ± 6. 88 vs 20. 83 ± 2. 48, 58. 80 ± 6. 75 vs 37. 63 ± 2. 96, 50. 00 ± 2. 36 vs 35. 00 ± 2. 82, 66. 00 ± 4. 04 vs 55. 00 ± 2. 60); and all the differences were statistically significant (all P<0. 05). Conclusions Liver injury was more severe in ANP rats with obesity, which may be related to the fact that obesity may enhance the activation of TLR4/NLRP3 signal pathway and result in the release of more inflammatory factors.

Toll-like receptors (TLRs) is a kind of pattern recognition receptor which widely exists on the cell membrane. It is a natural immune system component which can regulate the inflammatory response of the body participating in the signal transduction of cells and play an important role in the endogenous immune response. But the excessive inflammatory reaction initiated by TLRs can make the immune function of the body unbalanced and damage the function of many organs. The earliest discovered TLR4 is a transmembrane protein, almost express in all kinds of cell. Lots of study show it is closely related to the occurrence and development of acute pancreatitis (AP). The role and mechanism of TLR4 in AP will be reviewed in this article.