Comparison of clinical efficacy and safety between interventional embolization and craniotomy clipping for anterior circulation aneurysms.

Objective: To investigate the clinical efficacy and safety of interventional embolization in the treatment of anterior circulation aneurysms. Methods: Eighty patients with anterior circulation aneurysms admitted to People's Hospital of Leshan from June 2019 to December 2021 were retrospectively analyzed. According to the different surgical methods, they were divided into two groups: the observation group and the control group. Patients in the observation group were given interventional embolization, while those in the control group were given craniotomy clipping. The surgical efficacy, postoperative neurological function and quality of life, surgical prognosis and surgical complications of the two groups were compared. Results: The intraoperative blood loss and hospitalization time in the observation group were lower than those in the control group (p<0.05). The scores of the Hunt-Hess and modified Rankin scale in the observation group were significantly lower than those in the control group three months after surgery (p<0.05). The good prognosis rate of the observation group was higher than that of the control group (p<0.05). Moreover, the complication rate of the observation group was 12.50%, which was significantly lower than 32.50% in the control group (p<0.05). Conclusion: Interventional embolization shows the advantages of minimally invasive procedures such as shorter operative times and shorter hospital stays. It has better clinical safety because it can significantly improve the neurological function and quality of life of patients, improve the prognosis of patients, and reduce the incidence of complications.

Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/ß-Catenin and Sonic Hedgehog Pathways.

Neuroinflammation plays important roles in the pathogenesis and progression of altered neurodevelopment, sensorineural hearing loss, and certain neurodegenerative diseases. Hyperoside (quercetin-3-O-ß-D-galactoside) is an active compound isolated from Hypericum plants. In this study, we investigate the protective effect of hyperoside on neuroinflammation and its possible molecular mechanism. Lipopolysaccharide (LPS) and hyperoside were used to treat HT22 cells. The cell viability was measured by MTT assay. The cell apoptosis rate was measured by flow cytometry assay. The mRNA expression levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were determined by quantitative reverse transcription polymerase chain reaction. The levels of oxidative stress indices superoxide dismutase (SOD), reactive oxygen species (ROS), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) were measured by the kits. The expression of neurotrophic factor and the relationship among hyperoside, silent mating type information regulation 2 homolog-1 (SIRT1) and Wnt/ß-catenin, and sonic hedgehog was examined by western blotting. In the LPS-induced HT22 cells, hyperoside promotes cell survival; alleviates the level of IL-1ß, IL-6, IL-8, TNF-α, ROS, MDA, Bax, and caspase-3; and increases the expression of CAT, SOD, GSH, Bcl-2, BDNF, TrkB, and NGF. In addition, hyperoside upregulated the expression of SIRT1. Further mechanistic investigation showed that hyperoside alleviated LPS-induced inflammation, oxidative stress, and apoptosis by upregulating SIRT1 to activate Wnt/ß-catenin and sonic hedgehog pathways. Taken together, our data suggested that hyperoside acts as a protector in neuroinflammation.

[Synthesis and antitumor activity of cinnamoyloxy phosphonate derivatives].

In search of more effective anticancer agents, twelve compounds were designed and synthesized via microwave-assisted reactions of cinnamoyl chloride with α-hydroxyphosphonate. The structures of all the compounds were confirmed by IR, NMR and elemental analysis. Bioassay of the compounds were tested. They exhibited certain antitumor activities. Especially, compound 3c had obvious inhibitory effect on growth of SGC-7901 cells in vitro at 20 µmol·L(-1), and compound 3h showed better inhibitory effect on growth of SGC-7901 cells in vitro at 5 µmol·L(-1), the inhibition ratio were 68.8% and 48.0%, respectively.

Relationship between anion gap and in-hospital mortality in intensive care patients with liver failure: a retrospective propensity score matching analysis.

OBJECTIVES: To elucidate the association between anion gap (AG) and in-hospital mortality in intensive care patients with liver failure. METHODS: Demographic and clinical characteristics of intensive care patients with liver failure in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database were collected, and binomial logistic and Cox regression was conducted to investigate the association between AG and in-hospital mortality. The area under the receiver operating characteristic (ROC) curve (AUC) was conducted to characterize the performance of AG in predicting in-hospital mortality, and was compared with the albumin corrected anion gap (ACAG) and the End-Stage Liver Disease (MELD) score. The Kaplan-Meier curve was plotted for in-hospital survival analysis of AG and patients with liver failure. The propensity score matching (PSM) analysis was performed to mitigate selection bias. RESULTS: AG was an independent risk factor for in-hospital mortality in intensive care patients with liver failure. Before PSM, the AUCs of AG, ACAG, and MELD were 0.666, 0.682, and 0.653, respectively. After PSM, the AUCs of AG, ACAG, and MELD scores were 0.645, 0.657, and 0.645, respectively, and there is no difference in the predictive performance of the three indicators upon comparison. Compared with the low-AG (≤20 mmol/L) group, the hazard ratio (HR) for in-hospital death of the high-AG (>20 mmol/L) group was determined to be 2.1472 (before PSM)/1.8890 (after PSM). CONCLUSIONS: AG is associated with in-hospital mortality in intensive care patients with liver failure and demonstrates a moderate predictive value, which is comparable to the predictive power of the MELD score. AG may serve as an indirect marker of in-hospital mortality of patients with liver failure by reflecting the degree of metabolic acidosis.

Whole serum as cell protection reagent in cell shipment at low or room temperature.

To maintain cell viability and characteristics physiological over long time or long-distance cell shipment is critical to promote the collaborative efforts in the research field of cell biology. Herein, we investigated the possibility of different concentration of fetal bovine serum as transport cell reagent. Cell suspension of three different mammalian cell lines were transported in 1.5 mL tube under different temperature conditions. Cell viability was closely related to environmental temperature and shipment time. No significant difference of cell survival rate was observed between 2-8 â„ƒ and 8-16 â„ƒ groups, under these two temperature conditions, reagent containing above 50 % FBS showed the best protection effect to maintain over 80 % cell survival rate. After 10 days of cell shipment under 2-16 â„ƒ environmental temperature, C3H10 cells exhibited the same multiple differentiation ability, 143B cells had the same capability of proliferation, migration and invasion, LX-2 cells showed the same activation state with TGF-ß stimulation. Three cell lines maintained their primary characteristics after long time cell shipment. This entire shipment process does not require the maintenance of specific temperatures, humidity and container, providing a low-costing and convenient way for cell shipment between long distance laboratories.

GATA4 Forms a Positive Feedback Loop with CDX2 to Transactivate MUC2 in Bile Acids-Induced Gastric Intestinal Metaplasia.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids. Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens. GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa. Conclusions: GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

Silencing of ALOX15 reduces ferroptosis and inflammation induced by cerebral ischemia-reperfusion by regulating PHD2/HIF2α signaling pathway.

OBJECTIVE: To investigate the potential mechanism of arachidonic acid deoxyribozyme 15 (ALOX15) in ferroptosis and inflammation induced by cerebral ischemia reperfusion injury. METHODS: The mice and cell models of cerebral ischemia-reperfusion injury were constructed. Western Blot was used to detect the protein expression levels of ALOX15, glutathione peroxidase (GPX4), hypoxia-inducible factor-2α (HIF-2α), prolyl hydroxylase (PHD) and inflammatory factors (NLRP3, IL-1ß, IL-18) in brain tissues and cells. Cell proliferation activity was detected by CCK-8 method. LDH assay was used to detect the release of lactate dehydrogenase. TTC staining was used to observe cerebral infarction. RESULTS: In cerebral ischemia-reperfusion mice and cell models, the expression of ALOX15 protein was increased, the expression of GPX4, a key marker of ferroptosis was decreased, and silencing of ALOX15 down-regulated the GPX4 expression. HIF-2α expression was down-regulated in animal and cell models of cerebral ischemia reperfusion, and silencing of ALOX15 increased the HIF-2α expression by inhibiting PHD2 expression. Inhibition of ALOX15 expression reduced inflammatory factors levels (NLRP3, IL-1ß, and IL-18) in cerebral ischemia. Inhibitor of PHD2 (IXOC-4) alleviating brain injury and cell death induced by cerebral ischemia reperfusion and stabilize HIF-2α expression in vivo. CONCLUSION: The expression of ALOX15 was up-regulated in cerebral ischemia-reperfusion animals and cells model. Inhibition of ALOX15 up-regulated the GPX4 expression, and promoted HIF-2α expression by inhibiting PHD2, thus alleviating ferroptosis and inflammation caused by cerebral ischemia-reperfusion injury.

Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study.

Inflammation plays a role in the pathogenesis of acute-on-chronic liver failure (ACLF), however, whether there is a causal relationship between inflammation and ACLF remains unclear. A two-sample Mendelian randomization (MR) approach was used to investigate the causal relationship between systemic inflammatory regulators and ACLF. The study analyzed 41 cytokines and growth factors from 8,293 individuals extracted from a genome-wide association study (GWAS) meta-analysis database involving 253 ACLF cases and 456,095 controls. Our results showed that lower stem cell factor (SCF) levels, lower basic fibroblast growth factor (bFGF) levels and higher Interleukin-13 (IL-13) levels were associated with an increased risk of ACLF (OR = 0.486, 95% CI = 0.264-0.892, p = 0.020; OR = 0.323, 95% CI = 0.107-0.972, p = 0.044; OR = 1.492, 95% CI = 1.111-2.004, p = 0.008, respectively). In addition, genetically predicted ACLF did not affect the expression of systemic inflammatory regulators. Our results indicate that cytokines play a crucial role in the pathogenesis of ACLF. Further studies are needed to determine whether these biomarkers can be used to prevent and treat ACLF.

Diagnostic accuracy of arterial spin labeling in differentiating between primary central nervous system lymphoma and high-grade glioma: a systematic review and meta-analysis.

BACKGROUND: Existing studies have confirmed the accuracy of arterial spin labeling (ASL) in differentiating between primary central nervous system lymphoma (PCNSL) and high-grade glioma (HGG). We aimed to consolidate the existing evidence with a meta-analysis. METHODS: Six literature databases were searched for relevant papers. After assessing the quality of studies, bivariate regression was performed, and the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic score, diagnostic odds ratio (DOR), and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve were calculated, along with the corresponding 95% confidence intervals (CIs). Deeks' test was used to determine risk of publication bias. RESULTS: Ten high-quality studies, comprising 151 patients with PCNSL and 455 with HGG, were included. The pooled SEN was 0.79 (95% CI: 0.72-0.85), pooled SPE was 0.90 (95% CI: 0.84-0.94), pooled PLR was 8.07 (95% CI: 5.01-13.02), pooled NLR was 0.23 (95% CI: 0.17-0.32), pooled diagnostic score was 3.56 (95% CI: 2.94-4.18), and pooled DOR was 35.10 (95% CI: 18.83-65.45). The AUC of SROC was 0.86 (95% CI: 0.83-0.89). No publication bias was found. CONCLUSIONS: ASL demonstrated high diagnostic accuracy in differentiating between PCNSL and HGG.

Case Report: A rare case of young adult progressive familial intrahepatic cholestasis-type 3 with a novel heterozygous pathogenic variant of ABCB4.

Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive disorder with poor prognosis. It is caused by pathogenic variants of the ATP binding cassette subfamily B member 4 (ABCB4) gene and usually progresses from chronic cholestasis with or without jaundice to portal hypertension and end-stage liver disease within the first to second decade of life. Few reported PFIC-3 patients presented with atypical clinical symptoms, therefore, often misdiagnosed if without family history. Herein, we report a 16-year-old male who was admitted to our hospital due to acute episodes of jaundice and intense pruritus, subsequently progressed to end-stage liver disease. Laboratory examinations showed no evidence of liver injury caused by viral, autoimmune, drug or liver tumors. Ursodeoxycholic acid and dexamethasone did not relieve his symptoms and he underwent liver transplantation successfully. Targeted next-generation sequencing identified that the patient was a compound heterozygote for two missense mutations (c.959C > T/c.1429C > A) in the ABCB4 gene. The mutation c.1429C > A (p.Q477K) is a novel heterozygous mutation. We constructed a three-dimensional model of this novel pathogenic variant using the SWISS MODEL program and found that the patient's ABCB4 protein is an ATP hydrolysis deficient mutant. The postoperative pathological diagnosis showed intrahepatic cholestasis with progression to cirrhosis. Negative liver tissue immunohistochemistry of MDR3 was found in the explanted liver. The patient was diagnosed with PFIC-3, and his symptoms improved dramatically with liver transplantation. In conclusion, for young patients with acute cholestasis, pruritus, jaundice, growth retardation, and enlargement of the liver and spleen, the possibility of inherited metabolic liver diseases should be considered, detailed medical and family history should be collected, and metabolic screening tests as well as gene tests are necessary for correct diagnosis. Increasing the coverage of PFIC3 is meaningful and thus can improve the current understanding of this disease.

Canthaxanthin shows anti-liver aging and anti-liver fibrosis effects by down-regulating inflammation and oxidative stress in vivo and in vitro.

The elderly population is growing rapidly all over the world. The aging population has brought great medical pressure to the society. It is found that aging is one of the pathogenic factors of liver fibrosis and liver cancer. Therefore, it is very important to explore functional foods with anti-aging, anti-fibrosis and anti-liver cancer effect. Therefore, in this work, we studied the potential effects of Canthaxanthin on liver aging, liver fibrosis and liver cancer. Firstly, we established the aging modelof liver cells by using H2O2. On this basis, the anti-aging effect of Canthaxanthin was analyzed, and the results showed that Canthaxanthin could significantly alleviate the aging of liver cells through Sa-ß-Gal staining and analysis of the expression of aging related markers. In vivo, aged mice wereused as the animal model for studying the effect of anti-aging of Canthaxanthin. The results showed that Canthaxanthin could significantly alleviate the aging of liver in vivo. Further study show that Canthaxanthin may alleviatethe aging of liver cells by regulating SIRT6; Secondly, we evaluated the effect of Canthaxanthin on liver fibrosis. A model of liver fibrosis was established by CCl4. Masson and Sirius red staining showed that Canthaxanthin could significantly reduce the fibrosis area. Additionally, the level of liver inflammation was also reduced; Thirdly, the effect of Canthaxanthin on hepatoma cells has also been investigated. The resultsshowed that Canthaxanthin could promote the apoptosis of hepatoma cells in vivo and in vitro. To sum up, these results show that canthaxanthin can significantly alleviate liver aging and fibrosis, and Canthaxanthin can also promote the apoptosis of liver cancer cells, indicating that Canthaxanthin can be used as a potential drug or health food for the treatment of liveraging related diseases.

GGNBP2 Suppresses the Proliferation, Invasion, and Migration of Human Glioma Cells.

Gliomas are the most common and aggressive type of primary adult brain tumors. Although GGNBP2 has previously been considered to be a tumor suppressor gene, little is known about the association between GGNBP2 and glioma. In this study, we clearly demonstrated that GGNBP2 was downexpressed in glioma tissues, and its downexpression is related to the pathological grade and overall survival of patients with gliomas. Overexpression of GGNBP2 suppressed the proliferation, migration, and invasion of glioma cells. Mechanistically, we demonstrated that the PI3K/Akt and Wnt/ß-catenin signaling pathways were suppressed by GGNBP2 overexpression. In contrast, knockdown of GGNBP2 has precisely the opposite effect. Collectively, these data indicate that GGNBP2 shows tumor suppressive activity in human glioma cells and may stand out as a potential therapeutic target for glioma.

Serum contents of IL-23 and IL-17 in the patients with ulcerative colitis and the clinical significance.

AIM: To study the serum contents of IL-23 and IL-17 in the patients with ulcerative colitis and the clinical significance. METHODS: 40 patients with ulcerative colitis as UC group and 30 healthy people as control group were selected. The serum contents of IL-23 and IL-17 were determined bII ELISA. RESULTS: Serum contents of IL-23 AND IL-17 in UC group were higher than those in control group significantly (t=18.76, 21.48, P<0.01). Serum contents of IL-23 and IL-17 increase with the clinical symptoms. Serum contents of IL-23 AND IL-17 in severe patients were higher than those of mild and moderate patients significantly, and serum contents of IL-23 and IL-17 in mild patients were higher than those of moderate patients significantly. Serum contents of IL-23 were positively correlated to IL-17 significantly (r=0.548, P<0.01). CONCLUSION: IL-23 and IL-17 participates in the pathogenesis of ulcerative colitis. IL-23 may play a critical role in the development of UC through inducing production of IL-17.